bluuebunny/crossref_metadata_2025 huggingface dataset:
Brief Report: Impact of ART on Maternal Health After Cessation of Breastfeeding
Authors: Brummel Sean S. , Taha Taha E. , Angelidou Konstantia (Nadia) , Saidi Friday , Atuhaire Patience , Dula Dingase , Moodley Dhayendre , Matubu Allen , Chareka Gift , Nevrekar Neetal , Vhembo Tichaona , Fairlie Lee , Theron Gerhard , Mlay Pendo , George Kathleen , Basar Michael , Chakhtoura Nahida , Browning Renee , Fowler Mary Glenn , Currier Judith S. ,   for the IMPAACT 1077BF/FF PROMISE Study Team
Published: December 2020

IMPAACT PROMISE 1077BF/FF was a sequentially randomized study of pregnant and postpartum women living with HIV to investigate the efficacy and safety of antiretroviral therapy (ART). This Maternal Health Component investigated efficacy for the risk of developing AIDS or death; and safety among women randomized to continue ART (CTART: N = 289) or discontinue ART (N = 268) after cessation of breastfeeding or after confirmation of infant infection. No AIDS-defining illnesses were reported during follow-up in either arm. Adverse events of grade 3 or higher were more frequent in the CTART arm [hazard ratio = 1.78, 95% confidence interval: (1.05 to 3.02), P-value = 0.03]. The difference in adverse events in the 2 groups was mostly driven by moderate weight loss for women on the CTART arm.
Trauma results in immune cell-induced intestinal epithelial damage with subsequently increased sepsis rate
Authors: Mauser Martin , Kruger Deirdré , Pather Sugeshnee , Plani Frank
Published: December 2020

BACKGROUND

The detrimental effect of trauma on the immune system has been a subject of interest for decades. The gut-associated lymphoid tissue (GALT) of the bowel that encompasses different lymphocyte subpopulations may be an important pillar of human immunity in the context of trauma. Neither the short-term histological trauma-induced changes in the GALT nor its impact on the outcome after trauma surgery has been investigated.

METHODS

This prospective, longitudinal proof-of-concept study included patients who required damage-control surgery after abdominal gunshot wounds with small bowel involvement. Bowel specimens were obtained during the index and relook operations, and the T-lymphocytic quantity therein was analyzed via immunohistochemistry. We scrutinized how the lymphocyte structure and numbers of the GALT altered, and whether the extent and nature of these changes had an impact on the postoperative outcome with regard to septic and surgical complications.

RESULTS

A total of 31 damage-control patients were recruited for the study. The main histological changes between the index and relook specimen was a shift of CD8+ T cells from the lamina propria (LP) into the epithelium and a decrease of T lymphocytes in the LP. The significant increase of the intraepithelial CD8+ T cells was associated with a more extensive enterocyte apoptosis, and correlated significantly, positively with the number of postoperative septic complications.

CONCLUSION

Our data support that trauma induces an immune cell-driven impairment of the intestinal epithelium, as well as an increased apoptosis of lymphocytes in the LP, which is associated with a worse clinical outcome. The underlying mechanism suggests that a therapeutic approach to minimize apoptosis in the intestine may impact the outcome of severely injured trauma patients.

LEVEL OF EVIDENCE

Therapeutic/care/management, level lV.
Nonconvulsive Status Epilepticus With Neuropsychological Symptoms: Two Case Reports
Authors: Inatomi Yuichiro , Nakajima Makoto , Yonehara Toshiro
Published: December 2020

Nonconvulsive status epilepticus with neuropsychological symptoms other than aphasia or amnesia is rare. We report two such cases. Case 1, a 62-year-old man with a history of a subcortical hemorrhage in the right lateral temporal lobe and a brain infarct in the left medial temporo-occipital lobes, suddenly developed left unilateral spatial neglect and visual object agnosia. Diffusion-weighted imaging indicated status epilepticus, not stroke. His deficits resolved immediately after treatment with diazepam and phenytoin sodium. Case 2, a 61-year-old man with a history of brain infarcts in the right lateral temporal and left medial temporo-occipital lobes, suddenly developed global aphasia and cortical deafness. An MRI revealed no new lesions, including infarcts. An EEG revealed lateralized periodic discharges in the left temporo-parieto-occipital area, and single-photon emission computed tomography revealed a transient high-uptake lesion in the left temporoparietal lobes, indicating status epilepticus. His deficits also resolved immediately after treatment with diazepam and phenytoin sodium. The two patients’ neuropsychological symptoms—visual object agnosia and cortical deafness—were associated with focal nonconvulsive status epilepticus and were successfully treated with anti-epileptic medications. It is suggested that individuals with acute neuropsychological symptoms be diagnosed with MRI and/or EEG as well as CT for differential diagnoses other than cerebrovascular diseases.
Model-based evaluation of the impact of noncompliance with public health measures on COVID-19 disease control
Authors: Stoddard Madison , Van Egeren Debra , Johnson Kaitlyn , Rao Smriti , Furgeson Josh , White Douglas E. , Nolan Ryan P. , Hochberg Natasha , Chakravarty Arijit
Published: December 2020

The word ‘pandemic’ conjures dystopian images of bodies stacked in the streets and societies on the brink of collapse. Despite this frightening picture, denialism and noncompliance with public health measures are common in the historical record, for example during the 1918 Influenza pandemic or the 2015 Ebola epidemic. The unique characteristics of SARS-CoV-2—its high reproductive number (R0), time-limited natural immunity and considerable potential for asymptomatic spread—exacerbate the public health repercussions of noncompliance with biomedical and nonpharmaceutical interventions designed to limit disease transmission. In this work, we used game theory to explore when noncompliance confers a perceived benefit to individuals, demonstrating that noncompliance is a Nash equilibrium under a broad set of conditions. We then used epidemiological modeling to explore the impact of noncompliance on short-term disease control, demonstrating that the presence of a noncompliant subpopulation prevents suppression of disease spread. Our modeling shows that the existence of a noncompliant population can also prevent any return to normalcy over the long run. For interventions that are highly effective at preventing disease spread, however, the consequences of noncompliance are borne disproportionately by noncompliant individuals. In sum, our work demonstrates the limits of free-market approaches to compliance with disease control measures during a pandemic. The act of noncompliance with disease intervention measures creates a negative externality, rendering COVID-19 disease control ineffective in the short term and making complete suppression impossible in the long term. Our work underscores the importance of developing effective strategies for prophylaxis through public health measures aimed at complete suppression and the need to focus on compliance at a population level.
Effects of maternal deprivation and complex housing on pro-social behavior in rats: An automated, operant task examining motivation to liberate a trapped conspecific
Authors: Kalamari Aikaterini , Kentrop Jiska , Danesi Chiara Hinna , Graat Evelien J.M. , van IJzendoorn Marinus H. , Bakermans-Kranenburg Marian J. , Joëls Marian , van der Veen Rixt
Published: December 2020

Early life environment influences the development of various aspects of social behavior, particularly during sensitive developmental periods. Here, we aimed to study how challenges in the early postnatal period or (early) adolescence affect pro-social behavior. To this end, we adapted an existing paw operated liberation task to an automated operant task, to measure motivation (by progressively increasing required lever pressing) to liberate a trapped conspecific. Liberation of the trapped rat resulted either in social contact, or in liberation into a separate compartment. Additionally, a condition was tested in which both rats could freely move in two separate compartments and lever pressing resulted in social contact. When partners were not trapped, rats were more motivated to press the lever for opening the door than in either of the trapped configurations. Contrary to our expectation, the trapped configuration resulted in areducedmotivation to act. Early postnatal stress (24h maternal deprivation on postnatal day 3) did not affect behavior in the liberation task. However, rearing rats from early adolescence onwards in complex housing conditions (Marlau cages) reduced the motivation to door opening, both in the trapped and freely moving conditions, while motivation for a sucrose reward was not affected.
Chemical exhaustion of RPA in cancer treatment
Authors: VanderVere-Carozza Pamela S. , Pawelczak Katherine S. , Gavande Navnath S. , Jalal Shadia I. , Pollok Karen E. , Ekinci Elmira , Heyza Joshua , Patrick Steve M. , Turchi John J.
Published: December 2020

Replication protein A (RPA) plays essential roles in DNA replication, repair, recombination and the DNA-damage response (DDR). We have developed second generation RPA inhibitors (RPAi’s) that block the RPA-DNA interaction. These DNA-binding inhibitors (DBi’s) can elicit a state of cellular RPA exhaustion resulting in single agentin vitroanticancer activity across a broad spectrum of cancers andin vivoactivity in two non-small cell lung cancer models. The cellular response to RPAi treatment suggests a threshold exists before RPA inhibition induces cell death. Chemical RPA exhaustion potentiates the anticancer activity of other DDR inhibitors as well as traditional DNA damaging cancer therapeutics. Consistent with the chemical RPA exhaustion model, we demonstrate that the effects of RPAi on replication fork dynamics and DNA damage signaling are similar to other known DDR inhibitors. In accordance with the RPA threshold model, retrospective analysis of lung cancer patient data demonstrates high RPA expression as a negative prognostic biomarker for overall survival in smoking-related lung cancers. Similarly, relative expression of RPA is a predictive marker for response to chemotherapy. These observations are consistent with the increase in RPA expression serving as an adaptive mechanism that allows tolerance of the genotoxic stress resulting from carcinogen exposure. These data demonstrate a unique mechanism of action of RPAi’s eliciting a state of RPA exhaustion that impacts the DDR and may provide an effective therapeutic option for difficult to treat lung cancers.

Graphical Abstract
Modified N-linked glycosylation status predicts trafficking defective human Piezo1 channel mutations
Authors: Li Jinyuan Vero , Ng Chai-Ann , Cheng Delfine , Yao Mingxi , Guo Yang , Yu Ze-Yan , Ramaswamy Yogambha , Ju Lining Arnold , Kuchel Philip W , Feneley Michael P , Fatkin Diane , Cox Charles D
Published: December 2020

Mechanosensitive channels are integral membrane proteins that sense mechanical stimuli. Like all membrane proteins, they pass through biosynthetic quality control in the endoplasmic reticulum and Golgi that results in them reaching their destination at the plasma membrane. Here we show that N-linked glycosylation of two highly conserved asparagine residues in the ‘cap’ region of mechanosensitive Piezo1 channels are necessary for the mature protein to reach the plasma membrane. Both mutation of these asparagines (N2294Q/N2331Q) and treatment with an enzyme that hydrolyses N-linked oligosaccharides (PNGaseF) eliminates the fully glycosylated mature Piezo1 protein. The N-glycans in the cap are a pre-requisite for higher-order glycosylation in the ‘propeller’ regions, which are present in loops that are essential for mechanotransduction. Importantly, trafficking-defective Piezo1 variants linked to generalized lymphatic dysplasia and bicuspid aortic valve display reduced fully N-glycosylated protein. The higher order glycosylation statusin vitrocorrelates with efficient membrane trafficking and will aid in determining the functional impact of Piezo1 variants of unknown significance.
Subtle changes in crosslinking drive diverse anomalous transport characteristics in actin-microtubule networks
Authors: Anderson S. J. , Garamella J. , Adalbert S. , McGorty R. J. , Robertson-Anderson R. M.
Published: December 2020

Anomalous diffusion in crowded and complex environments is widely studied due to its importance in intracellular transport, fluid rheology and materials engineering. Specifically, diffusion through the cytoskeleton, a network comprised of semiflexible actin filaments and rigid microtubules that interact both sterically and via crosslinking, plays a principal role in viral infection, vesicle transport and targeted drug delivery. Here, we elucidate the impact of crosslinking on particle diffusion in composites of actin and microtubules with actin-actin, microtubule-microtubule and actin-microtubule crosslinking. We analyze a suite of complementary transport metrics by coupling single-particle tracking and differential dynamic microscopy. Using these orthogonal techniques, we find that particles display non-Gaussian and non-ergodic subdiffusion that is markedly enhanced by cytoskeletal crosslinking of any type, which we attribute to suppressed microtubule mobility. However, the extent to which transport deviates from normal Brownian diffusion depends strongly on the crosslinking motif – with actin-microtubule crosslinking inducing the most pronounced anomalous characteristics – due to increased actin fluctuation heterogeneity. Our results reveal that subtle changes to actin-microtubule interactions can have dramatic impacts on diffusion in the cytoskeleton, and suggest that less mobile and more locally heterogeneous networks lead to more strongly anomalous transport.
AC. elegansgenome-wide RNAi screen for altered levamisole sensitivity identifies genes required for muscle function
Authors: Chaya Timothy , Patel Shrey , Smith Erin M. , Lam Andy , Miller Elaine N. , Clupper Michael , Kervin Kirsten , Tanis Jessica
Published: December 2020

At the neuromuscular junction (NMJ), postsynaptic ionotropic acetylcholine receptors (AChRs) transduce a chemical signal released from a cholinergic motor neuron into an electrical signal to induce muscle contraction. To identify regulators of postsynaptic function, we conducted a genome-wide RNAi screen for genes required for proper response to levamisole, a pharmacological agonist of ionotropic L-AChRs at theCaenorhabditis elegansNMJ. A total of 117 gene knockdowns were found to cause levamisole hypersensitivity, while 18 resulted in levamisole resistance. Our screen identified conserved genes important for muscle function including some that are mutated in congenital myasthenic syndrome, congenital muscular dystrophy, congenital myopathy, myotonic dystrophy, and mitochondrial myopathy. Of the genes found in the screen, we further investigated those predicted to play a role in endocytosis of cell surface receptors. Loss of the Epsin homologepn-1had opposing effects on the levels of postsynaptic L-AChRs and GABAAreceptors, resulting in increased and decreased abundance, respectively. This disrupts the balance of postsynaptic excitatory and inhibitory signaling, causing levamisole hypersensitivity. We also examined other genes that resulted in a levamisole hypersensitive phenotype when knocked down includinggas-1, which functions in Complex I of the mitochondrial electron transport chain. Consistent with altered ATP synthesis impacting levamisole response, treatment of wild-type animals with levamisole resulted in L-AChR dependent depletion of ATP levels. These results suggest that the paralytic effects of levamisole ultimately lead to metabolic exhaustion.
Implementing process improvement initiative: the role of visualisation and standardisation methods
Authors: Abubakre Mumin , Fayoumi Amjad , Eleburuike Ismail
Published: December 2020

Purpose

Due to the difficulties organisations face in implementing process improvement initiatives (PIIs), this research explores how visualisation and standardisation of business processes help organisations achieve PIIs to improve organisational performance.

Design/methodology/approach

A multi-staged case study strategy that analyse qualitative data and performs a process modelling analysis of quantitative data.

Findings

The paper makes two main contributions to existing knowledge. Firstly, it explains how taking the visualised and standardised methods on PIIs can reduce service delivery times and enhance organisational performance. Secondly, it demonstrates how adopting these dual methods offers a better chance of increasing organisational performance than using only a single method.

Research limitations/implications

Although the paper considers the flexibility in the standardisation of business processes as it gives scope for innovation and creativity on the part of the process, it did not consider if flexibility is possible without breaking the standardised working way. Hence, future research can consider this. Also, future research can hypothesise the BPM model and test for statistical generalisability.

Originality/value

The research offers new insight into how and when both visualisation and standardisation of PIIs can benefit organisations.
Effects of the poverty alleviation relocation program on diet quality among low-income households
Authors: Qiu Huanguang , Leng Ganxiao , Feng Xiaolong , Yang Sansi
Published: December 2020

Purpose

This paper aims to examine impacts of the poverty alleviation relocation (PAR) program on diet quality of low-income households in China. We explore the impact mechanism of relocation on diet quality and the heterogeneous effects of different relocation modes.

Design/methodology/approach

A fixed effects model is constructed using panel data of 1126 low-income households collected over three years in eight provinces of China. The PAR program provides a natural experiment which dramatically changes the living conditions surrounding farmers. We are able to identify the causal effects of relocation on diet quality free from selection bias.

Findings

The empirical results show that the PAR program improves diet quality of low-income households and that better market access and increasing incomes induced by relocation play an important role in this improvement. Improved market access significantly reduces the over-consumption of staple foods, whereas higher income significantly reduces the intake divergences of non-staple foods. The impacts of different relocation modes on diet quality are highly heterogeneous.

Practical implications

Our findings indicate that the PAR program benefits diet quality of low-income households through greater market access and increases in total household income. Market improvements and food subsidies are conducive to improving the diet quality of the low income.

Originality/value

Despite widespread evidences of healthy diets being associated with household environments and income, selection bias remains. This paper utilizes an exogenous program to explore the causal impacts of market access and family income on diet quality and to separate their different effects.
Article 786 of the Jordanian civil code: a potential gold mine for employers and a potential minefield for contractors
Authors: Haloush Haitham A. , Alhusban Ahmad Abed Alla , Massadeh Ali Abdel Mahdi
Published: December 2020

Purpose

This paper aims to highlight how the prevention principle may affect the rights and responsibilities of contractors under Jordanian law. In many instances, the application of legal theories and terminology of the Jordanian civil code (JCC), such as penalty clauses and produces a similar result to that under common law, such as prevention principle, and even if in some cases the route by which the result is reached differs.

Design/methodology/approach

This paper is based upon library research on primary and secondary sources. The author adopted the interpretive paradigm with its underlying subjectivist assumption. This paradigm creates different meanings and therefore different realities. This is particularly evident when studying legal notions, such as parties’ autonomy and decennial liability, from a comparative law perspective.

Findings

In many instances, the application of legal theories and terminology of the JCC, such as penalty clauses and produces a similar result to that under common law, such as the prevention principle, and even if in some cases the route by which the result is reached differs. However, it is difficult for judges and lawyers in Jordan to understand the legal principles of certain terms in the common law. This requires, to a certain extent, an understanding of the legal terms and concepts, particularly those originated from English law. For example, a thorough grasp of the prevention principle in Jordanian law remains unclear. Apparently, this can be met by training and capacity building sessions.

Originality/value

As far as the author is aware, this issue has not been researched comprehensively before from technical and legal standpoints. This paper represents the first attempt to examine the issues arising in this difficult and important subject.
Effects of endorser type and testimonials in direct-to-consumer prescription drug advertising (DTCA)
Authors: Rollins Brent , Huh Jisu , Bhutada Nilesh , Perri Matthew
Published: December 2020

Purpose

This study aims to examine the effects of different types of endorsers (expert vs consumer vs celebrity) in testimonial vs non-testimonial message contexts on consumers’ responses toward direct-to-consumer advertising (DTCA).

Design/methodology/approach

An online experiment was conducted with a 3 (endorser type: expert vs consumer vs celebrity) × 2 (message type: testimonial vs non-testimonial) plus control group (no endorser, no testimonial) factorial design to assess the various dependent variables.

Findings

Perceived source credibility and similarity was significantly different across the endorser types, and the expert endorser (i.e. a doctor) generated the highest mean level of source credibility, while consumer endorsers generate the highest mean source similarity. The interaction of endorser type and message type significantly impacted ad believability and skepticism. Specifically, the endorser type factor had a significant impact on the dependent variables only in the testimonial ad condition, but not in the non-testimonial ad condition. The effects were mediated by source credibility.

Originality/value

While the focused results show celebrities may not be the strongest choice to endorse when using testimonials, the overall lack of main effect of testimonials lends to the possibility of a plateauing of effects with the various appeals used in DTC ads. DTCA has now been around for over 20 years, and this study lends to the possibility consumers are becoming unaffected by the various appeals used by pharmaceutical manufactures and only respond when a multitude of personally relevant factors are in place.
Three early papers on self-neglect
Authors: Martineau Stephen
Published: December 2020

Purpose

The paper examines three English research papers on self-neglect, from 1957, 1966 and 1975, discussing them in the context of more recent thinking and the statutory framework in England.

Design/methodology/approach

In reviewing the three research papers, developments and points of continuity in the field of self-neglect were identified and are discussed in this paper.

Findings

In light of the findings of the three articles, the present paper traces some of the classificatory refinements in this field that have taken place since the papers were published, notably in respect of hoarding and severe domestic squalor. Some of the difficulties in making judgements about behaviour thought to breach societal norms are described, and the challenges practitioners face in intervening in cases, particularly where the person concerned is refusing assistance, are examined.

Originality/value

By drawing on the historical research context, the paper contributes to our current understanding of the field of self-neglect.
Beyond the workforce training pipeline: embracing the meandering stream of “whole of life” and career to strengthen the retention of health professionals rurally
Authors: Colbran Richard , Ramsden Robyn , Edwards Michael , O'Callaghan Emer , Karlson Dave
Published: December 2020

Purpose

While Australia has continued to invest in polices and strategies aimed at improving rural health service provision, many communities still confront a disproportionate share of the rural workforce shortage. The NSW Rural Doctors Network (RDN) contributes its perspectives about the importance of a whole of life career and the meandering stream concept to support the retention of health professionals rurally. We unpack these concepts and examine how they bring to light a new and useful approach to addressing rural workforce challenges and potentially contribute to building a stronger integrated care approach.

Design/methodology/approach

The approach used involved tapping into RDN's 30-years of experience in recruitment and retention of remote and rural health professionals, combined with insights from relevant existing and emerging evidence.

Findings

We suggest that reframing retention to consider a life stage approach to career will guide more effective targeting of rural health policies, workforce planning, collaborative approaches and allocation of incentives. We posit that an understanding and acceptance of modern lifestyles and career pathways, and a celebration of career commitment to serving rural communities, is necessary for successful recruitment and retention of Australia's future rural health workforce beyond the training pipeline.

Originality/value

We outline and visually represent RDN's meandering stream approach to building and retaining a capable rural health workforce through addressing life cycle and workforce level needs. This perspective paper draws on RDN's direct experience in the field.
Understanding resource commitment to R&D in multinational enterprises: a novel conceptual framework
Authors: le Duc Niels
Published: December 2020

Purpose

This paper aims to introduce and advocate the concept of resource commitment to better understand multinational enterprise (MNE) research and development (R&D) behavior.

Design/methodology/approach

Adopting a theory adaptation research design, this paper assesses the characteristics and antecedents associated with varying resource commitment positions. It does so in relation to MNE R&D activities, considering their importance to firm competitiveness and the recent increases in the number of locations and innovative activities a firm might choose to invest in.

Findings

The paper presents a framework showing that differences in resource commitment are more nuanced than expected. The evaluation of antecedents shows that the external environment, the purpose of R&D activities and firm experience influence the resource commitment position of a firm’s R&D activities.

Originality/value

The paper provides a pathway toward understanding of MNE R&D behavior, explaining observable differences in resource and commitment levels of R&D units. The presented framework offers MNE managers insight into when to adopt which resource commitment positions. It offers policymakers insights into the type of activities and the companies they need to attract to maximize the added value of firm’s investments in their country/region.
“Little Red Sandals”: female police officers' lived experience of investigating sexual violence
Authors: Bozga Adina , McDowall Almuth , Brown Jennifer
Published: December 2020

Purpose

Against a background of increasing workload and external criticism, the purpose of this paper is to expose the indelible memories impressed on female police officers dedicated to investigating allegations of rape and sexual violence.

Design/methodology/approach

Participants (n = 15) were female police officers working in a specialist sexual offences investigation unit in a large English Metropolitan Police Force. A semi-structured interview was employed to elicit their experiences as an example of “extreme” police work. Interpretative phenomenological analysis was used to develop themes elucidating psychological and physical impacts on officers and their coping strategies.

Findings

Personal consequences were framed within the conceptualisation of secondary trauma. Emergent findings revealed profound and lasting vicarious traumatisation. Participants reported feelings of depression, anxiety, suicidal ideation, intrusive imagery, altered beliefs and cognitions as well as disrupted intimacy with partners. Coping adaptations included sensory shutdown, avoidance, dissociation and a reduction in victim care.

Practical implications

The findings support the need to consider occupational interventions to address risk factors associated with caseload, tenure, personal experience of neglect (e.g. in childhood), and the permeability of work and family boundaries for such exceptional policing tasks.

Originality/value

The paper contributes to a nascent literature on stress in “extreme” police work. The theoretical contribution is the focus on the emotional and physical aspects of vicarious trauma, which have been less well understood than cognitive aspects. The practice implications stress the need for targeted support activities given the profound psychological consequences of prolonged exposure to distressing material.
Sequence analysis and specificity of distinct types of menaquinone methyltransferases indicate the widespread potential of methylmenaquinone production in bacteria and archaea
Authors: Wilkens Dennis , Meusinger Reinhard , Hein Sascha , Simon Jörg
Published: December 2020

Menaquinone (MK) serves as an essential membranous redox mediator in various electron transport chains of aerobic and anaerobic respiration. In addition, the composition of the quinone/quinol pool has been widely used as a biomarker in microbial taxonomy. The HemN‐like class C radical SAM methyltransferases (RSMTs) MqnK, MenK and MenK2 have recently been shown to facilitate specific menaquinone methylation reactions at position C‐8 (MqnK/MenK) or C‐7 (MenK2) to synthesize 8‐methylmenaquinone, 7‐methylmenaquinone and 7,8‐dimethylmenaquinone. However, the vast majority of protein sequences from the MqnK/MenK/MenK2 family belong to organisms, whose capacity to produce methylated menaquinones has not been investigated biochemically. Here, representative putative menK and menK2 genes from Collinsella tanakaei and Ferrimonas marina were individually expressed in Escherichia coli (wild‐type or ubiE deletion mutant) and the corresponding cells were found to produce methylated derivatives of the endogenous MK and 2‐demethylmenaquinone. Cluster and phylogenetic analyses of 828 (methyl)menaquinone methyltransferase sequences revealed signature motifs that allowed to discriminate enzymes of the MqnK/MenK/MenK2 family from other radical SAM enzymes and to identify C‐7‐specific menaquinone methyltransferases of the MenK2 subfamily. This study will help to predict the methylation status of the quinone/quinol pool of a microbial species (or even a microbial community) from its (meta)genome and contribute to the future design of microbial quinone/quinol pools in a Synthetic Biology approach.
Combining chemical analysis, sensory profile, CATA, preference mapping and chemometrics to establish the consumer quality standard of Camembert‐type cheeses
Authors: Los Paulo Ricardo , Simões Deise Rosana Silva , Benvenutti Laís , Zielinski Acácio Antonio Ferreira , Alberti Aline , Nogueira Alessandro
Published: December 2020

This study aimed to establish a consumer quality standard for Camembert‐type cheeses, combining chemical analysis, sensory profile, CATA (Check‐All‐That‐Apply), preference mapping and chemometrics. The cheeses were manufactured using three different cultures (‘O’ mesophilic homofermentative; ‘T’ thermophilic and ‘LD’ mesophilic heterofermentative) and assessed at different ripening times (14, 21 and 28 days). The results showed a clear separation between consumers, with a higher number preferring the LD‐type cheeses. The use of different sensory methods clarifies the consumers' choice regarding the cheese, with CATA proving to be an effective, low‐cost method for characterisation of the cheeses, with the cheese made with LD‐type culture the most accepted. These results show that this methodology can be used to develop consumer acceptable products through the standardisation of the manufacturing protocol.
The Effectiveness of White‐Collar Crime Enforcement: Evidence from the War on Terror
Authors: Nguyen Trung
Published: December 2020

This paper analyzes the impact of changes in regulatory priorities and resource allocation on criminal enforcement of white‐collar criminal activities. Using the 9/11 terrorist attacks as a shock to the FBI's priorities and allocation of investigative resources, as well as variation in the Muslim population in the United States, I examine whether prioritization of counterterrorism investigations after 9/11 is associated with weaker enforcement of laws targeting white‐collar crime. I then use a difference‐in‐differences estimation to study the magnitude of any increase in white‐collar crime resulting from reduced oversight. I find a significantly greater reduction in white‐collar criminal cases referred by FBI field offices that shifted more of their investigative focus away from white‐collar crime to counterterrorism. Further, geographic areas in the jurisdictions of FBI field offices with greater shifts in attention from white‐collar crime to counterterrorism experienced greater increases in wire fraud, illegal insider‐trading activities, and fraud within financial institutions.
Decision-Making with Uncertainty
Authors: Diggle Peter J. , Gowers Tim , Kelly Frank , Lawrence Neil
Published: December 2020

In emergency situations like the coronavirus pandemic, decisions must be made quickly, with only partial information. But good decisions are still possible using risk–benefit analysis. By Peter J. Diggle, Tim Gowers, Frank Kelly and Neil Lawrence
Creation, destruction, and COVID: Heeding the call of country, bringing things into balance
Authors: Smith Aunty Shaa , Smith Neeyan , Daley Lara , Wright Sarah , Hodge Paul
Published: December 2020

On Gumbaynggirr Country (mid‐north coast New South Wales, Australia), an act of violence against the sacredness of life and Country resulted in Wirriiga, the Two Sisters, making the sea. When the waters rose, the people made their way back to their homeland by following a gut‐string bridge made by Dunggiirr, the Koala Brothers. While the people were on the bridge, mischievous Baalijin, the eastern quoll, threatened to chop it down and made waves that nearly washed them off. Baalijin challenges complacency and forces change, and on that understanding in this article we consider what it means to be living this present time of instability and changes wrought by coronavirus disease 2019 (COVID‐19); ours is a perspective grounded in story and Gumbaynggirr Law/Lore. We write as Yandaarra, a research collective guided by the Old Fellas (ancestors) and led by Aunty Shaa Smith, storyholder for Gumbaynggirr Country, and her daughter Neeyan Smith, a young Gumbaynggirr woman. Learning from a Gumbaynggirr‐led understanding of COVID‐19—as one manifestation of Baalijin and relationships fallen out of balance—re‐situates the pandemic in wider and longer histories of colonisation and destructive patterns of existence and broken agreements. Those learnings prompt us to call for Juungambala—work involved in setting things right as a way to heal. Let Baalijin and COVID‐19 be the wake‐up call that forces the change that Country (and we) need.
Molecular evolution and deorphanization of bitter taste receptors in a vampire bat
Authors: LU Qin , JIAO Hengwu , WANG Yi , NORBU Ngawang , ZHAO Huabin
Published: December 2020

Bats represent the largest dietary radiation in a single mammalian order, and have become an emerging model group for studying dietary evolution. Taste receptor genes have proven to be molecular signatures of dietary diversification in bats. For example, all 3 extant species of vampire bats have lost many bitter taste receptor genes (Tas2rs) in association with their dietary shift from insectivory to sanguivory. Indeed, only 8 full‐length Tas2rs were identified from the high‐quality genome of the common vampire bat (Desmodus rotundus). However, it is presently unknown whether these bitter receptors are functional, since the sense of taste is less important in vampire bats, which have an extremely narrow diet and rely on other senses for acquiring food. Here, we applied a molecular evolutionary analysis of Tas2rs in the common vampire bat compared with non‐vampire bats. Furthermore, we provided the first attempt to deorphanize all bitter receptors of the vampire bat using a cell‐based assay. We found that all Tas2r genes in the vampire bat have a level of selective pressure similar to that in non‐vampire bats, suggesting that this species must have retained some bitter taste functions. We demonstrated that 5 of the 8 bitter receptors in the vampire bat can be activated by some bitter compounds, and observed that the vampire bat generally can not detect naturally occurring bitter compounds examined in this study. Our study demonstrates functional retention of bitter taste in vampire bats as suggested by cell‐based functional assays, calling for an in‐depth study of extra‐oral functions of bitter taste receptors.
Comparison of three techniques for genetic estimation of effective population size in a critically endangered parrot
Authors: Olah G. , Stojanovic D. , Webb M. H. , Waples R. S. , Heinsohn R.
Published: December 2020

Understanding the current population size of small, spatially aggregating populations of species is essential for their conservation. Reliable estimates of the effective population size (Ne) can be used to provide an early warning for conservation managers of the risks to genetic viability of small populations. Critically endangered, migratory swift parrots Lathamus discolor exist in a single panmictic population in Australia. In their Tasmanian breeding range, they are at severe risk of predation by introduced sugar gliders, exacerbated by deforestation. We used three genetic approaches to estimate Ne using DNA samples genotyped by microsatellite markers and existing life‐history data of swift parrots. Based on all samples, we revealed small contemporary Ne estimates across methods (range: 44–140), supporting the need to urgently address threatening processes. Using the 0.5 Ne/N ratio calculated from demographic data suggests that the minimum potential contemporary population size is below 300 individual swift parrots. This is considerably lower than the published estimates derived from expert elicitation, and accords with modeled estimates of extinction risk in this species. Our study has important implications for other threatened species with unknown population sizes and demonstrates that by utilizing available genetic data, reasonable estimates of Ne can be derived.
Analysis of fish population size distributions confirms cessation of fishing in marine protected areas
Authors: White J. Wilson , Yamane Mark T. , Nickols Kerry J. , Caselle Jennifer E.
Published: December 2020

The number of protected areas that restrict or prohibit harvest of wild populations is growing. In general, protected areas are expected to increase the abundance of previously‐harvested species. Whether a protected area achieves this expectation is typically evaluated by assessing trends in abundance after implementation. However, the underlying assumption that harvest has actually ceased is rarely tested directly. Determining whether illegal harvest (poaching) has continued in a protected area is important to planning enforcement and adaptive management. Here, we estimated harvest rates for four kelp forest fish species inside marine protected areas (MPAs) and non‐MPA reference sites in the California Channel Islands, from 2003 (when MPAs were implemented) to 2017. We estimated harvest by fitting a size‐structured population model to survey data. Overall, harvest rates were effectively zero in MPAs but much higher in non‐MPA sites. This indicates successful adherence to MPA regulations, and possible displacement of fishing effort to reference sites. However, some poaching was detected in two MPA sites, highlighting the importance of assessing this quantity. This modeling approach could provide a tool to complement the long‐term management of MPA networks, particularly given the difficulty of acquiring harvest rate data at the spatial scale of individual MPAs.
Inhibition of fatty acid synthase with FT‐4101 safely reduces hepatic de novo lipogenesis and steatosis in obese subjects with non‐alcoholic fatty liver disease: Results from two early‐phase randomized trials
Authors: Beysen Carine , Schroeder Patricia , Wu Eric , Brevard Julie , Ribadeneira Maria , Lu Wei , Dole Kiran , O'Reilly Terry , Morrow Linda , Hompesch Marcus , Hellerstein Marc K. , Li Kelvin , Johansson Lars , Kelly Patrick F.
Published: December 2020

Aims

To assess the therapeutic potential of fatty acid synthase (FASN) inhibition with FT‐4101, a potent, selective, orally bioavailable, small‐molecule by (a) evaluating the dose−response of single FT‐4101 doses (3, 6 and 9 mg) on hepatic de novo lipogenesis (DNL) in healthy participants (Study 1) and (b) demonstrating the safety, tolerability and efficacy on hepatic steatosis after 12 weeks of FT‐4101 dosing in patients with non‐alcoholic fatty liver disease (NAFLD; Study 2).

Materials and Methods

In Study 1, three sequential cohorts of healthy men (n = 10/cohort) were randomized to receive a single dose of FT‐4101 (n = 5/cohort) or placebo (n = 5/cohort) followed by crossover dosing after 7 days. Hepatic DNL was assessed during fructose stimulation from 13C‐acetate incorporation. In Study 2, men and women with NAFLD (n = 14) randomly received 12 weeks of intermittent once‐daily dosing (four cycles of 2 weeks on‐treatment, followed by 1 week off‐treatment) of 3 mg FT‐4101 (n = 9) or placebo (n = 5). Steady‐state DNL based on deuterated water labelling, hepatic steatosis using magnetic resonance imaging‐proton density fat fraction and sebum lipids and circulating biomarkers were assessed.

Results

Single and repeat dosing of FT‐4101 were safe and well tolerated. Single FT‐4101 doses inhibited hepatic DNL dose‐dependently. Twelve weeks of 3 mg FT‐4101 treatment improved hepatic steatosis and inhibited hepatic DNL. Decreases in sebum sapienate content with FT‐4101 at week 11 were not significant compared to placebo and rebounded at week 12. Biomarkers of liver function, glucose and lipid metabolism were unchanged.

Conclusions

Inhibition of FASN with 3 mg FT‐4101 safely reduces hepatic DNL and steatosis in NAFLD patients.
Genetically determined lean mass and dietary response
Authors: Dash Satya , Paterson Andrew D.
Published: December 2020

Weight loss attenuates many obesity‐related co‐morbidities, but is difficult to sustain with dietary change. Dietary adherence, not macronutrient composition, is a better predictor of weight loss. Weight loss‐induced endocrine changes promote food intake and increase energy efficiency, contributing to the difficulty with dietary adherence and weight regain. Macronutrient preference is partly genetically determined, suggesting that personalized dietary interventions might be more successful. In this issue, Li et al. report that a genetic risk score comprising the cumulative weighted effects of variants previously associated with increased lean mass is associated with increased satiety and weight loss 6 months after initiating a low‐ but not a high‐fat diet. The effects were attenuated by 2 years. These findings suggest that genetic variants may influence response to specific diet. Further studies are necessary to assess whether genetically determined lean mass is causally associated with dietary response. Significant progress has recently been made in identifying additional genetic determinants of lean mass, which will enable such investigations and potentially inform future nutritional studies.
EEG alpha–theta dynamics during mind wandering in the context of breath focus meditation: An experience sampling approach with novice meditation practitioners
Authors: Rodriguez‐Larios Julio , Alaerts Kaat
Published: December 2020

Meditation practice entails moments of distraction dominated by self‐generated thoughts (i.e. mind wandering). Initial studies assessing the neural correlates of mind wandering in the context of meditation practice have identified an important role of theta (4–8 Hz) and alpha (8–14 Hz) neural oscillations. In this study, we use a probe‐caught experience sampling paradigm to assess spectral changes in the theta‐alpha frequency range during mind wandering in the context of breath focus meditation. Electroencephalography (EEG) was measured in 25 novice meditation practitioners during a breath focus task in which they were repeatedly probed to report whether they were focusing on their breath or thinking about something else. Mind wandering episodes were associated with an increase in the amplitude and a decrease in the frequency of theta (4–8 Hz) oscillations. Conversely, alpha oscillations (8–14 Hz) were shown to decrease in amplitude and increase in frequency during mind wandering relative to breath focus. In addition, mind wandering episodes were shown to be accompanied by increased harmonicity and phase synchrony between alpha and theta rhythms. Because similar spectral changes in the theta‐alpha frequency range have been reported during controlled cognitive processes involving memory and executive control, we speculate that mind wandering and controlled processes could share some neurocognitive mechanisms. From a translational perspective, this study indicates that oscillatory activity in the theta‐alpha frequency range could form adequate parameters for developing EEG‐neurofeedback protocols aimed at facilitating the detection of mind wandering during meditation practice.