bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental spatial and temporal variability and its role in non-favoured mutant dynamics
Authors: Farhang-Sardroodi Suzan , Darooneh Amir H. , Kohandel Mohammad , Komarova Natalia L.
Published: August 2019

Understanding how environmental variability (or randomness) affects evolution is of fundamental importance for biology. The presence of temporal or spatial variability significantly affects the competition dynamics in populations, and gives rise to some counterintuitive observations. In this paper, we consider both birth–death (BD) or death–birth (DB) Moran processes, which are set up on a circular or a complete graph. We investigate spatial and temporal variability affecting division and/or death parameters. Assuming that mutant and wild-type fitness parameters are drawn from an identical distribution, we study mutant fixation probability and timing. We demonstrate that temporal and spatial types of variability possess fundamentally different properties. Under temporal randomness, in a completely mixed system, minority mutants experience (i) higher than neutral fixation probability and a higher mean conditional fixation time, if the division rates are affected by randomness and (ii) lower fixation probability and lower mean conditional fixation time if the death rates are affected. Once spatial restrictions are imposed, however, these effects completely disappear, and mutants in a circular graph experience neutral dynamics, but only for the DB update rule in case (i) and for the BD rule in case (ii) above. In contrast to this, in the case of spatially variable environment, both for BD/DB processes, both for complete/circular graph and both for division/death rates affected, minority mutants experience a higher than neutral probability of fixation. Fixation time, however, is increased by randomness on a circle, while it decreases for complete graphs under random division rates. A basic difference between temporal and spatial kinds of variability is the types of correlations that occur in the system. Under temporal randomness, mutants are spatially correlated with each other (they simply have equal fitness values at a given moment of time; the same holds for wild-types). Under spatial randomness, there are subtler, temporal correlations among mutant and wild-type cells, which manifest themselves by cells of each type ‘claiming’ better spots for themselves. Applications of this theory include cancer generation and biofilm dynamics.
Mechanistic modelling of prostate-specific antigen dynamics shows potential for personalized prediction of radiation therapy outcome
Authors: Lorenzo Guillermo , Pérez-García Víctor M. , Mariño Alfonso , Pérez-Romasanta Luis A. , Reali Alessandro , Gomez Hector
Published: August 2019

External beam radiation therapy is a widespread treatment for prostate cancer. The ensuing patient follow-up is based on the evolution of the prostate-specific antigen (PSA). Serum levels of PSA decay due to the radiation-induced death of tumour cells and cancer recurrence usually manifest as a rising PSA. The current definition of biochemical relapse requires that PSA reaches nadir and starts increasing, which delays the use of further treatments. Also, these methods do not account for the post-radiation tumour dynamics that may contain early information on cancer recurrence. Here, we develop three mechanistic models of post-radiation PSA evolution. Our models render superior fits of PSA data in a patient cohort and provide a biological justification for the most common empirical formulation of PSA dynamics. We also found three model-based prognostic variables: the proliferation rate of the survival fraction, the ratio of radiation-induced cell death rate to the survival proliferation rate, and the time to PSA nadir since treatment termination. We argue that these markers may enable the early identification of biochemical relapse, which would permit physicians to subsequently adapt patient monitoring to optimize the detection and treatment of cancer recurrence.
Attachment-based mechanisms underlying capture and release of pollen grains
Authors: Ito Shuto , Gorb Stanislav N.
Published: August 2019

Successful insect pollination can be achieved by a sequence of numerous attachment and detachment events at various biological surfaces. However, the quantitative measurements of pollen adhesion on biological surfaces have been poorly studied so far. We performed atomic force microscopy adhesion measurements of pollen on two most important floral parts for Asteraceae in a course of pollination: the stigma and style ofHypochaeris radicataplant.The results indicated distinct adhesive properties of them—the pollen adhesion on stigmatic surfaces drastically increased over prolonged contact time, while the pollen adhesion increase on stylar surfaces was rather restrained. Based on the observation with cryo-scanning electron microscopy, we explained the experimental results by the presence of morphological features in form of flexible stigmatic papillae that may play a crucial role in enhancing both capillary attraction and van der Waals forces. The distinct adhesive properties seemingly originate from the unique adhesive tasks that each of the floral parts requires to achieve successful pollination. The insights into the adhesive interaction between pollen and the floral parts, obtained in the present study, may lead to better understanding of pollination mechanisms, which are strongly related to our food production. Additionally, the novel pollen adhesive mechanisms learned from the stigma of the studied Asteraceae plant can inspire biomimetic designs of spontaneous gripping systems.
The impact of balloon-expandable transcatheter aortic valve replacement on concomitant mitral regurgitation: a comprehensive computational analysis
Authors: Caballero Andrés , Mao Wenbin , McKay Raymond , Sun Wei
Published: August 2019

The aortic and mitral valves function in a reciprocal interdependent fashion. However, the impact of transcatheter aortic valve replacement (TAVR) on the aortic–mitral continuity and severity of mitral regurgitation (MR) are poorly understood. In this study, a comprehensive engineering analysis was performed to investigate the impact of TAVR on MR severity and left heart dynamics in a retrospective patient case who harbours bicuspid aortic valve stenosis and concomitant functional MR. The TAVR procedure was computer simulated using a balloon-expandable valve, and the impact of three implantation heights on aortic–mitral coupling, MR severity and device performance were analysed. The accuracy and predictability of the computer modelling framework were validated with pre- and post-operative echo data. The highest deployment model resulted in higher stresses in the native leaflets, contact radial force and stent recoil, while the midway implantation model gave better haemodynamic performance and MR reduction in this patient case. Although the regurgitant volume decreased (less than 10%) for the three deployment configurations, no significant differences in MR severity improvement and mitral leaflet tethering were found. Acute improvement in MR was (i) due to the mechanical compression of the stent against the aortic–mitral curtain, (ii) due to an immediate drop in the ventricular pressure and transmitral pressure gradient. Albeit a single real clinical case, it is our hope that such detailed engineering computational analysis could shed light on the underlying biomechanical mechanisms of TAVR impact on MR.
Connecting empirical phenomena and theoretical models of biological coordination across scales
Authors: Zhang Mengsen , Beetle Christopher , Kelso J. A. Scott , Tognoli Emmanuelle
Published: August 2019

Coordination in living systems—from cells to people—must be understood at multiple levels of description. Analyses and modelling of empirically observed patterns of biological coordination often focus either on ensemble-level statistics in large-scale systems with many components, or on detailed dynamics in small-scale systems with few components. The two approaches have proceeded largely independent of each other. To bridge this gap between levels and scales, we have recently conducted a human experiment of mid-scale social coordination specifically designed to reveal coordination at multiple levels (ensemble, subgroups and dyads) simultaneously. Based on this experiment, the present work shows that, surprisingly, a single system of equations captures key observations at all relevant levels. It also connects empirically validated models of large- and small-scale biological coordination—the Kuramoto and extended Haken–Kelso–Bunz (HKB) models—and the hallmark phenomena that each is known to capture. For example, it exhibits both multistability and metastability observed in small-scale empirical research (via the second-order coupling and symmetry breaking in extended HKB) and the growth of biological complexity as a function of scale (via the scalability of the Kuramoto model). Only by incorporating both of these features simultaneously can we reproduce the essential coordination behaviour observed in our experiment.
Assortative mating frames establishment in a young island bird population
Authors: Engler Jan O. , Sacher Thomas , Coppack Timothy , Bairlein Franz
Published: August 2019

Successful island colonizations are key events to understand range dynamic processes, but studying a young population right after it reaches establishment is a rare opportunity in natural systems. The genetic structure of a recently established population may offer unique insights into its colonization history and demographic processes that are important for a successful colonization. Here, we studied the population genetics of a recently established island population of Eurasian blackbirds (Aves:Turdus merula) located on the island of Heligoland in the German North Sea. Using microsatellites, we genotyped the majority of the island population, including the nestlings, over a 4-year period between 2004 and 2007. We also genotyped high numbers of migrants on stopover and mainland individuals, as they are potential founders of the island population. We identified two genetic clusters that comply with the migrating and mainland birds. While most of the island birds belong to the mainland cluster, some breeding individuals and a low fraction of the offspring belong to the genetic cluster found in migrating individuals with almost no admixture between the two, pointing to assortative mating acting on the island population. We did not find any evidence for founder events and detected deviations from the Hardy–Weinberg equilibrium that disappeared in cohorts of older age that coincide with a lower number of siblings in older cohorts. The observed genetic patterns unravel a complex colonization history to which migratory and mainland birds have contributed and which is characterized by assortative mating. Further research will be directed towards habitat selection and phenotypic differences as potential drivers of assortative mating in this island population.
Novel cooperative antipredator tactics of an ant specialized against a snake
Authors: Jono Teppei , Kojima Yosuke , Mizuno Takafumi
Published: August 2019

Eusocial insects can express surprisingly complex cooperative defence of the colony. Brood and reproductive castes typically remain in the nest and are protected by workers' various antipredator tactics against intruders. In Madagascar, a myrmicine ant,
Aphaenogaster swammerdami
, occurs sympatrically with a large blindsnake,
Madatyphlops decorsei
. As blindsnakes generally specialize on feeding on termites and ants brood by intruding into the nest, these snakes are presumably a serious predator on the ant. Conversely, a lamprophiid snake,
Madagascarophis colubrinus
, is considered to occur often in active
A
.
swammerdami
nests without being attacked. By presenting
M
.
colubrinus
,
M
.
decorsei
and a control snake,
Thamnosophis lateralis
, at the entrance of the nest, we observed two highly specialized interactions between ants and snakes: the acceptance of
M
.
colubrinus
into the nest and the cooperative evacuation of the brood from the nest for protection against the ant-eating
M
.
decorsei
. Given that
M
.
colubrinus
is one of the few known predators of blindsnakes in this area,
A
.
swammerdami
may protect their colonies against this blindsnake by two antipredator tactics, symbiosis with
M
.
colubrinus
and evacuation in response to intrusion by blindsnakes. These findings demonstrate that specialized predators can drive evolution of complex cooperative defence in eusocial species.
Reply to comment on Couzi
et al
. (2018): a phenomenological model for structural phase transitions in incommensurate alkane/urea inclusion compounds
Authors: Christensen Kirsten , Williams P. Andrew , Patterson Rhian , Palmer Benjamin A. , Couzi Michel , Guillaume François , Harris Kenneth D. M.
Published: August 2019

In a recent paper (Couzi
et al.
2018
R. Soc. open sci.
5
, 180058. (
doi:10.1098/rsos.180058
)), we proposed a new phenomenological model to account for the I↔II↔“III” phase sequence in incommensurate
n
-alkane/urea inclusion compounds, which represents an alternative interpretation to that proposed in work of Toudic
et al.
In a Comment (Toudic
et al.
2019
R. Soc. open sci.
6
, 182073. (
doi:10.1098/rsos.182073
)), Toudic
et al.
have questioned our assignment of the superspace group of phase II of
n
-nonadecane/urea, which they have previously assigned, based on a (3 + 2)-dimensional superspace, as C222
1
(00
γ
)(10
δ
). In this Reply, we present new results from a comprehensive synchrotron single-crystal X-ray diffraction study of
n
-nonadecane/urea, involving measurements as a detailed function of temperature across the I↔II↔“III” phase transition sequence. Our results demonstrate conclusively that “main reflections” (
h, k, l
, 0) with
h+k
odd are observed in phase II of
n
-nonadecane/urea (including temperatures in phase II that are just below the transition from phase I to phase II), in full support of our assignment of the (3+1)-dimensional superspace group P2
1
2
1
2
1
(00
γ
) to phase II. As our phenomenological model is based on phase II and phase “III” of this incommensurate material having the

same

(3+1)-dimensional superspace group P2
1
2
1
2
1
(00
γ
), it follows that the new X-ray diffraction results are in full support of our phenomenological model.
Loss of cultural song diversity and the convergence of songs in a declining Hawaiian forest bird community
Authors: Paxton Kristina L. , Sebastián-González Esther , Hite Justin M. , Crampton Lisa H. , Kuhn David , Hart Patrick J.
Published: August 2019

The effects of population decline on culturally transmitted behaviours in animals have rarely been described, but may have major implications to population viability. Learned vocal signals in birds are of critical importance to behaviours associated with reproduction, intrasexual interactions and group cohesion, and the complexity of vocal signals such as song can serve as an honest signal of an individual's quality as well as the viability of a population. In this study, we examined how rapid population declines recently experienced by Hawaiian honeycreepers on the island of Kaua‘i (USA) may have influenced the diversity, complexity and similarity of learned honeycreeper songs. We analysed the acoustic characteristics of songs recorded during three time periods over a 40-year time frame for three species of declining Kaua‘i honeycreepers. We detected a loss of song complexity and diversity over the 40-year time period that paralleled dramatic population declines. Concurrent with the loss of complexity, we also found that the acoustic characteristics of the three honeycreepers' songs became more similar to one another. To our knowledge, this is the first documentation of convergence of acoustic characteristics among rapidly declining species. The reduction in song complexity and diversity and convergence of songs not only signals a loss of culturally transmitted behaviours in these endemic Hawaiian honeycreepers, but also potential challenges to the recovery of these rapidly declining species. Moreover, the present study highlights that there is a ‘hidden’ cost to declining populations beyond just the loss of individuals that is not often considered, the loss of culturally transmitted social behaviours.
Variation in life-history traits amongDaphniaand its relationship to species-level responses to phosphorus limitation
Authors: Hartnett Rachel
Published: August 2019

Currently organisms are experiencing changes in their environment at an unprecedented rate. Therefore, the study of the contributions to and responses in traits linked to fitness is crucial, as they have direct consequences on a population's success in persisting under such a change.Daphniais used as a model organism as the genus contains keystone primary consumers in aquatic food webs. A life-history table experiment (LHTE) using four species ofDaphniawas conducted to compare variation in life-history traits among species across two different environmental conditions (high and low phosphorus availability). Results indicate that the food quality environment had the most impact on life-history traits, while genetic contributions to traits were higher at the species-level than clonal-level. Higher trait variation and species-level responses to P-limitation were more evident in reproductive traits, while growth traits were found to be less affected by food quality and had less variation. Exploring trait variation and potential plasticity in organisms is increasingly important to consider as a potential mechanism for population persistence given the fluctuations in environmental stressors we are currently experiencing.
A fully coupled subwavelength resonance approach to filtering auditory signals
Authors: Ammari Habib , Davies Bryn
Published: August 2019

The aim of this paper is to understand the behaviour of a large number of coupled subwavelength resonators. We use layer potential techniques in combination with numerical computations to study an acoustic pressure wave scattered by a graded array of subwavelength resonators. Using this approach, the spatial frequency separation properties of such an array can be understood. Our set-up is inspired by the graded structure of cochlear hair cells on the surface of the basilar membrane. We compute the resonant modes of the system and explore the model's ability to decompose incoming signals. We propose a mathematical explanation for phenomena identified with the cochlea's ‘travelling wave’ behaviour and tonotopic frequency map.
Silicon isotopes in Arctic and sub-Arctic glacial meltwaters: the role of subglacial weathering in the silicon cycle
Authors: Hatton Jade E. , Hendry Katharine R. , Hawkings Jonathan R. , Wadham Jemma L. , Opfergelt Sophie , Kohler Tyler J. , Yde Jacob C. , Stibal Marek , Žárský Jakub D.
Published: August 2019

Glacial environments play an important role in high-latitude marine nutrient cycling, potentially contributing significant fluxes of silicon (Si) to the polar oceans, either as dissolved silicon (DSi) or as dissolvable amorphous silica (ASi). Silicon is a key nutrient in promoting marine primary productivity, contributing to atmospheric CO
2
removal. We present the current understanding of Si cycling in glacial systems, focusing on the Si isotope (δ
30
Si) composition of glacial meltwaters. We combine existing glacial δ
30
Si data with new measurements from 20 sub-Arctic glaciers, showing that glacial meltwaters consistently export isotopically light DSi compared with non-glacial rivers (+0.16‰ versus +1.38‰). Glacial δ
30
Si
ASi
composition ranges from −0.05‰ to −0.86‰ but exhibits low seasonal variability. Silicon fluxes and δ
30
Si composition from glacial systems are not commonly included in global Si budgets and isotopic mass balance calculations at present. We discuss outstanding questions, including the formation mechanism of ASi and the export of glacial nutrients from fjords. Finally, we provide a contextual framework for the recent advances in our understanding of subglacial Si cycling and highlight critical research avenues for assessing potential future changes in these environments.
Areawise significance tests for windowed recurrence network analysis
Authors: Lekscha Jaqueline , Donner Reik V.
Published: August 2019

Many time-series analysis techniques use sliding window approaches or are repeatedly applied over a continuous range of parameters. When combined with a significance test, intrinsic correlations among the pointwise analysis results can make falsely positive significant points appear as continuous patches rather than as isolated points. To account for this effect, we present an areawise significance test that identifies such false-positive patches. For this purpose, we numerically estimate the decorrelation length of the statistic of interest by calculating correlation functions between the analysis results and require an areawise significant point to belong to a patch of pointwise significant points that is larger than this decorrelation length. We apply our areawise test to results from windowed traditional and scale-specific recurrence network analysis in order to identify dynamical anomalies in time series of a non-stationary Rössler system and tree ring width index values from Eastern Canada. Especially, in the palaeoclimate context, the areawise testing approach markedly reduces the number of points that are identified as significant and therefore highlights only the most relevant features in the data. This provides a crucial step towards further establishing recurrence networks as a tool for palaeoclimate data analysis.
Spatial heterogeneity in subglacial drainage driven by till erosion
Authors: Kasmalkar Indraneel , Mantelli Elisa , Suckale Jenny
Published: August 2019

The distribution and drainage of meltwater at the base of glaciers sensitively affects fast ice flow. Previous studies suggest that thin meltwater films between the overlying ice and a hard-rock bed channelize into efficient drainage elements by melting the overlying ice. However, these studies do not account for the presence of soft deformable sediment observed underneath many West Antarctic ice streams, and the inextricable coupling that sediment exhibits with meltwater drainage. Our work presents an alternate mechanism for initiating drainage elements such as canals where meltwater films grow by eroding the sediment beneath. We conduct a linearized stability analysis on a meltwater film flowing over an erodible bed. We solve the Orr–Sommerfeld equation for the film flow, and we compute bed evolution with the Exner equation. We identify a regime where the coupled dynamics of hydrology and sediment transport drives a morphological instability that generates spatial heterogeneity at the bed. We show that this film instability operates at much faster time scales than the classical thermal instability proposed by Walder. We discuss the physics of the instability using the framework of ripple formation on erodible beds.
Low-load pathogen spillover predicts shifts in skin microbiome and survival of a terrestrial-breeding amphibian
Authors: Becker C. Guilherme , Bletz Molly C. , Greenspan Sasha E. , Rodriguez David , Lambertini Carolina , Jenkinson Thomas S. , Guimarães Paulo R. , Assis Ana Paula A. , Geffers Robert , Jarek Michael , Toledo Luís Felipe , Vences Miguel , Haddad Célio F. B.
Published: August 2019

Wildlife disease dynamics are strongly influenced by the structure of host communities and their symbiotic microbiota. Conspicuous amphibian declines associated with the waterborne fungal pathogen
Batrachochytrium dendrobatidis
(Bd) have been observed in aquatic-breeding frogs globally. However, less attention has been given to cryptic terrestrial-breeding amphibians that have also been declining in tropical regions. By experimentally manipulating multiple tropical amphibian assemblages harbouring natural microbial communities, we tested whether Bd spillover from naturally infected aquatic-breeding frogs could lead to Bd amplification and mortality in our focal terrestrial-breeding host: the pumpkin toadlet
Brachycephalus pitanga
. We also tested whether the strength of spillover could vary depending on skin bacterial transmission within host assemblages. Terrestrial-breeding toadlets acquired lethal spillover infections from neighbouring aquatic hosts and experienced dramatic but generally non-protective shifts in skin bacterial composition primarily attributable to their Bd infections. By contrast, aquatic-breeding amphibians maintained mild Bd infections and higher survival, with shifts in bacterial microbiomes that were unrelated to Bd infections. Our results indicate that Bd spillover from even mildly infected aquatic-breeding hosts may lead to dysbiosis and mortality in terrestrial-breeding species, underscoring the need to further investigate recent population declines of terrestrial-breeding amphibians in the tropics.
Tracing back the origin of pumpkins (Cucurbita pepossp.pepoL.) in Mexico
Authors: Castellanos-Morales Gabriela , Ruiz-Mondragón Karen Y. , Hernández-Rosales Helena S. , Sánchez-de la Vega Guillermo , Gámez Niza , Aguirre-Planter Erika , Montes-Hernández Salvador , Lira-Saade Rafael , Eguiarte Luis E.
Published: August 2019

Cucurbita pepois an economically important crop, which consists of cultivatedC. pepossp.pepo, and two wild taxa (C. pepossp.fraternaandC. pepossp.ovifera).We aimed at understanding the domestication and the diversity ofC. pepoin Mexico. We used two chloroplast regions and nine nuclear microsatellite loci to assess the levels of genetic variation and structure forC. pepossp.pepo's landraces sampled in 13 locations in Mexico, five improved varieties, oneC. pepossp.fraternapopulation and ornamentalC. pepossp.ovifera. We tested four hypotheses regarding the origin ofC. pepossp.pepo's ancestor through approximate Bayesian computation:C. pepossp.oviferaas the ancestor;C. pepossp.fraternaas the ancestor; an unknown extinct lineage as the ancestor; andC. pepossp.pepoas hybrid fromC. pepossp.oviferaandC. pepossp.fraternaancestors.Cucurbita pepossp.peposhowed high genetic variation and low genetic differentiation.Cucurbita pepossp.fraternaandC. pepossp.peposhared two chloroplast haplotypes. The three subspecies were well differentiated for microsatellite loci.Cucurbita pepossp.fraternawas probablyC. pepossp.pepo's wild ancestor, but subsequent hybridization between taxa complicate definingC. pepossp.pepo's ancestor.
Unpacking mating success and testing Bateman’s principles in a human population
Authors: Borgerhoff Mulder Monique , Ross Cody T.
Published: August 2019

Human marriage systems, characterized by long-term partnerships and extended windows of parental care, differ from the mating systems of pulsed or seasonally breeding non-human animals in which Bateman’s principles were originally tested. These features, paradigmatic of but not unique to humans, complicate the accurate measurement of mating success in evaluating Bateman’s three principles. Here, we unpack the concept of mating success into distinct components: number of partners, number of years partnered, the timing of partnerships, and the quality of partners. Drawing on longitudinal records of marriage and reproduction collected in a natural-fertility East African population over a 20-year period, we test and compare various models of the relationship between mating success and reproductive success (RS), and show that an accurate assessment of male and female reproductive behaviour requires consideration of all major components of mating success. Furthermore, we demonstrate that while Bateman’s third principle holds when mating success is defined in terms of years married, women’s fitness increases whereas men’s fitness decreases from an increase in the number of marriage partners, holding constant the total effective duration of marriages. We discuss these findings in terms of the distinct, sex-specific pathways through which RS can be optimized, and comment on the contribution of this approach to the broader study of sexual selection.
Real-time Hearing Threshold Determination of Auditory Brainstem Responses by Cross-correlation Analysis
Authors: Wang Haoyu , Li Bei , Lu Yan , Han Kun , Sheng Haibin , Zhou Jialei , Qi Yumeng , Wang Xueling , Huang Zhiwu , Song Lei , Hua Yunfeng
Published: August 2019

Auditory brainstem response (ABR) serves as an objective indication of auditory perception at given sound level and is nowadays widely used in hearing function assessment. Despite efforts for automation over decades, hearing threshold determination by machine algorithm remains unreliable and thereby still rely on visual identification by trained personnel. Here, we described a procedure for automatic threshold determination that can be used in both animal and human ABR tests. The method terminates level averaging of ABR recordings upon detection of time-locked waveform through cross-correlation analysis. The threshold level was then indicated by a dramatic increase in the sweep numbers required to produce “qualified” level averaging. A good match was obtained between the algorithm outcome and the human readouts. Moreover, the method varies the level averaging based on the cross-correlation, thereby adapting to the signal-to-noise ratio of single sweep recordings. These features empower a robust and fully automated ABR test.
A systematic review of medical and clinical research landscapes and quality in Malaysia and Indonesia [REALQUAMI]: the review protocol
Authors: Chew Boon-How , Ying Lim Poh , Huey Lee Shaun Wen , Devaraj Navin Kumar , Ismail @ Daud Adibah Hanim , Shamsuddin Nurainul Hana , Jahn Kassim Puteri Shanaz , Rashid Aneesa Abdul , Fernandez Aaron , Zakuan Noraina Muhamad , Teoh Soo Huat , Abdullah Akiza Roswati , Ali Hanifatiyah , Abdul Manap Abdul Hadi , Mohamad Fadzilah , Widyahening Indah S.
Published: August 2019

Background

Research landscapes and quality may change in many ways. Much research waste has been increasingly reported. Efforts to improve research performance will need good data on the profiles and performance of past research.

Purpose

To describe the characteristics and quality of clinical and biomedical research in Malaysia and Indonesia.

Methods

A search will be conducted in PubMed, EMBASE, CINAHL and PsycINFO to identify for published clinical and biomedical research from 1962 to 2017 from Malaysia and/or Indonesia.

Additional search will also be conducted in MyMedR (for Malaysian team only). Studies found will be independently screened by a team of reviewers, relevant information will be extracted and quality of articles will be assessed. As part of quality control, another reviewer will independently assess 10-20% of the articles extracted. In Phase 1, the profiles of the published research will be reported descriptively. In Phase 2, a research quality screening tool will be validated to assess research quality based on three major domains of relevance, credibility of the methods and usefulness of the results. Associations between the research characteristics and quality will be analysed. The independent effect of each of the determinant will be quantified in multivariable regression analysis. Longitudinal trends of the research profiles, health conditions in different settings will be explored. Depending on the availability of resources, this review project may proceed according to the different clinical and biomedical disciplines in sequence.

Discussion

Results of this study will serve as the ‘baseline’ data for future evaluation and within country and between countries comparison. This review may also provide informative results to stakeholders of the evolution of research conduct and performance from the past till now. The longitudinal and prospective trends of the research profiles and quality could provide suggestions on improvement initiatives. Additionally, health conditions or areas in different settings, and whether they are over- or under-studied may help future prioritization of research initiatives and resources.
Health Care Provider Compliance with the HIPAA Right of Individual Access: a Scorecard and Survey (Revised)
Authors: McGraw Deven , Fitter Nasha , Taylor Lisa Belliveau
Published: August 2019

Background

Historically, patients have had difficulty obtaining copies of their medical records, notwithstanding the legal right to do so. In 2018, a study of 83 top hospitals found discrepancies between those hospitals’ published information and telephone survey responses regarding their processes for release of records to patients, indicating noncompliance with the HIPAA right of individual access.

Objective

Assess state of compliance with the HIPAA right of access across a broader range of health care providers and in the context of real records requests from patients.

Methods

Evaluate the degree of compliance with the HIPAA right of access 1) through telephone surveys of health care institutions regarding release of records to patients and 2) by scoring the responses of a total of 210 health care providers to actual patient record requests against the HIPAA right of access requirements. (51 of those providers were part of an initial cohort of 51 scored for an earlier version of this paper.)

Results

Based on the scores of responses of 210 health care providers to record requests and the responses of nearly 3000 healthcare institutions to telephone surveys, more than 50% of health care providers are out of compliance with the HIPAA right of access. The most common failure was refusal to send records to patient or patient’s designee in the form and format requested by the patient, with 86% of noncompliance due to this factor. The number of phone calls required to obtain records in compliance with HIPAA, and the lack of consistency in provider responses to actual requests, makes the records retrieval process a challenging one for patients.

Conclusions

Recent federal proposals prioritize patient access to medical records through certified electronic health record (EHR) technology, but access by patients to their complete clinical records via EHRs is years away. In the meantime, health care providers need to focus more attention on compliance with the HIPAA right of access, including better training of staff on HIPAA requirements. Greater enforcement of the law will help motivate providers to prioritize this issue.
Cell-surface receptors enable perception of extracellular cytokinins
Authors: Antoniadi Ioanna , Novák Ondřej , Gelová Zuzana , Johnson Alexander , Plíhal Ondřej , Vain Thomas , Simerský Radim , Mik Václav , Karady Michal , Pernisová Markéta , Plačková Lenka , Opassathian Korawit , Hejátko Jan , Robert Stéphanie , Friml Jiří , Doležal Karel , Ljung Karin , Turnbull Colin
Published: August 2019

Cytokinins are mobile multifunctional plant hormones with roles in development and stress resilience 1,2. Although cytokinin receptors are substantially localised to the endoplasmic reticulum 3–5, the cellular sites of cytokinin perception continue to be debated 1,6,7. Several cytokinin types display bioactivity 8,9 and recently a cell-specific cytokinin gradient was reported in roots 10. Yet, the importance of spatially heterogeneous cytokinin distribution and the specific cytokinin(s) that account for the different responses remain unclear. Here we show that cytokinin perception by plasma membrane receptors is an effective path for cytokinin response in root cells. Readout from a Two Component Signalling cytokinin-specific reporter (TCSn::GFP;11) is closely matched to intracellular cytokinin content, yet a proportion of bioactive cytokinins are detected in the extracellular fluid. Using cytokinins covalently linked to beads that could not pass the plasma membrane, we demonstrate that strong TCSn activation still occurs and that this response is greatly diminished in cytokinin receptor mutants. Although intracellular receptors play significant roles, we argue for a revision of concepts of cytokinin perception to include the spatial dimensions. In particular, selective ligand-receptor affinities, cellular localisation and tissue distribution of bioactive cytokinins, their receptors, transporters and inactivation enzymes appear all to be components of the signalling regulatory mechanisms.
One-time learning in a biologically-inspired Salience-affected Artificial Neural Network (SANN)
Authors: Remmelzwaal Leendert A , Ellis George F R , Tapson Jonathan
Published: August 2019

In this paper we introduce a novel Salience Affected Artificial Neural Network (SANN) that models the way neuromodulators such as dopamine and noradrenaline affect neural dynamics in the human brain by being distributed diffusely through neocortical regions. This allows one-time learning to take place through strengthening entire patterns of activation at one go. We present a model that accepts a salience signal, and returns a reverse salience signal. We demonstrate that we can tag an image with salience with only a single training iteration, and that the same image will then produces the highest reverse salience signal during classification. We explore the effects of salience on learning via its effect on the activation functions of each node, as well as on the strength of weights in the network. We demonstrate that a salience signal improves classification accuracy of the specific image that was tagged with salience, as well as all images in the same class, while penalizing images in other classes. Results are validated using 5-fold validation testing on MNIST and Fashion MNIST datasets. This research serves as a proof of concept, and could be the first step towards introducing salience tagging into Deep Learning Networks and robotics.
Pathway and network embedding methods for prioritizing psychiatric drugs
Authors: Pershad Yash , Guo Margaret , Altman Russ B.
Published: August 2019

One in five Americans experience mental illness, and roughly 75% of psychiatric prescriptions do not successfully treat the patient’s condition. Extensive evidence implicates genetic factors and signaling disruption in the pathophysiology of these diseases. Changes in transcription often underlie this molecular pathway dysregulation; individual patient transcriptional data can improve the efficacy of diagnosis and treatment. Recent large-scale genomic studies have uncovered shared genetic modules across multiple psychiatric disorders—providing an opportunity for an integrated multi-disease approach for diagnosis. Moreover, network-based models informed by gene expression can represent pathological biological mechanisms and suggest new genes for diagnosis and treatment. Here, we use patient gene expression data from multiple studies to classify psychiatric diseases, integrate knowledge from expert-curated databases and publicly available experimental data to create augmented disease-specific gene sets, and use these to recommend disease-relevant drugs. From Gene Expression Omnibus, we extract expression data from 145 cases of schizophrenia, 82 cases of bipolar disorder, 190 cases of major depressive disorder, and 307 shared controls. We use pathway-based approaches to predict psychiatric disease diagnosis with a random forest model (78% accuracy) and derive important features to augment available drug and disease signatures. Using protein-protein-interaction networks and embedding-based methods, we build a pipeline to prioritize treatments for psychiatric diseases that achieves a 3.4-fold improvement over a background model. Thus, we demonstrate that gene-expression-derived pathway features can diagnose psychiatric diseases and that molecular insights derived from this classification task can inform treatment prioritization for psychiatric diseases.
Genomic insights into the Archaea inhabiting an Australian radioactive legacy site
Authors: Vázquez-Campos Xabier , Kinsela Andrew S. , Bligh Mark W. , Payne Timothy E. , Wilkins Marc R. , Waite T. David
Published: August 2019

During the 1960s, small quantities of radioactive materials were co-disposed with chemical waste at the Little Forest Legacy Site (LFLS, Sydney, Australia). The microbial function and population dynamics in a waste trench during a rainfall event have been previously investigated using shotgun metagenomics. This revealed a broad abundance of candidate and potentially undescribed taxa in this iron-rich, radionuclide-contaminated environment.

Here, applying genome-based metagenomic methods, we recovered 37 refined archaeal MAGs (≥50% completeness, ≤10% redundancy) from 10 different major lineages. They were, mainly, included in four DPANN lineages without standing nomenclature (LFWA-I to IV) and Methanoperedenaceae (ANME-2D).

While most of the new DPANN lineages show reduced genomes with limited central metabolism typical of other DPANN, the orders under the LFWA-III lineage, ‘Ca. Gugararchaeales’ and ‘Ca. Anstonellales’, may constitute distinct orders with a more comprehensive central metabolism and anabolic capabilities within the Micrarchaeota phylum.

The new Methanoperedens spp. MAGs, together with previously published data, suggests metal ions as the ancestral electron acceptors during the anaerobic oxidation of methane while the respiration of nitrate/nitrite via molybdopterin oxidoreductases would have been a secondary acquisition. The presence of genes for the biosynthesis of polyhydroxyalkanoates in most Methanoperedens also appears to be a widespread characteristic of the genus for carbon accumulation.

We formally propose 22 new candidate taxa based on data analysed in this manuscript, as well as four missing formal taxa definitions and two new candidate species based on extant data. We present evidence of four new DPANN lineages and six non-conspecific Methanoperedens, while exploring their uniqueness, potential role in elemental cycling, and evolutionary history.
Sequences Dimensionality-Reduction by K-mer Substring Space Sampling Enables Effective Resemblance- and Containment-Analysis for Large-Scale omics-data
Authors: Yi Huiguang , Lin Yanling , Jin Wenfei
Published: August 2019

We proposed a new sequence sketching technique named k-mer substring space decomposition (kssd), which sketches sequences via k-mer substring space sampling instead of local-sensitive hashing. Kssd is more accurate and faster for resemblance estimation than other sketching methods developed so far. Notably, kssd is robust even when two sequences are of very different sizes. For containment analysis, kssd slightly outperformed mash screen—its closest competitor—in accuracy, while took testing datasets of 110,535 times less space occupation and consumed 2,523 times less CPU time than mash screen—suggesting kssd is suite for quick containment analysis for almost the entire omics datasets deposited in NCBI. We detailed the kssd algorithm, provided proofs of its statistical properties and discussed the roots of its superiority, limitations and future directions. Kssd is freely available under an Apache License, Version 2.0 (https://github.com/yhg926/public_kssd)
Crystal structure of the M5 muscarinic acetylcholine receptor
Authors: Vuckovic Ziva , Gentry Patrick R. , Berizzi Alice E. , Hirata Kunio , Varghese Swapna , Thompson Geoff , van der Westhuizen Emma T. , Burger Wessel A.C. , Rahmani Raphaёl , Valant Celine , Langmead Christopher J. , Lindsley Craig W. , Baell Jonathan , Tobin Andrew B. , Sexton Patrick M. , Christopoulos Arthur , Thal David M.
Published: August 2019

The human M5 muscarinic acetylcholine receptor (mAChR) has recently emerged as an exciting therapeutic target for treating a range of disorders, including drug addiction. However, a lack of structural information for this receptor subtype has limited further drug development and validation. Here we report a high-resolution crystal structure of the human M5 mAChR bound to the clinically used inverse agonist, tiotropium. This structure allowed for a comparison across all five mAChR family members that revealed important differences in both orthosteric and allosteric sites that could inform the rational design of selective ligands. These structural studies together with chimeric swaps between the extracellular regions of the M2 and M5 mAChR further revealed the structural insight into “kinetic-selectivity”, where ligands show differential residency times between related family members. Collectively, our study provides important insights into the nature of orthosteric and allosteric ligand interaction across the mAChR family that could be exploited for the design of selective ligands.

Significance Statement

The five subtypes of the muscarinic acetylcholine receptors (mAChRs) are expressed throughout the central and peripheral nervous system where they play a vital role in physiology and pathologies. Recently, the M5 mAChR subtype has emerged as an exciting drug target for the treatment of drug addiction. We have determined the atomic structure of the M5 mAChR bound to the clinically used inverse agonist tiotropium. The M5 mAChR structure now allows for a full comparison of all five mAChR subtypes and reveals subtle differences in the extracellular loop (ECL) regions of the receptor that mediate orthosteric and allosteric ligand selectivity. Together these findings open the door for future structure-based design of selective drugs that target this therapeutically important class of receptors.
The effect of liver enzymes on body composition: a Mendelian randomization study
Authors: Liu Jun Xi , Yeung Shiu Lun Au , Kwok Man Ki , Leung June Yue Yan , Hui Lai Ling , Leung Gabriel Matthew , Schooling C. Mary
Published: August 2019

Background

Higher alanine transaminase (ALT) is positively associated with diabetes but inversely associated with body mass index (BMI) in Mendelian randomization (MR) studies, suggesting liver function may affect body composition. To clarify, we assessed the association of liver function with muscle and fat mass observationally with two-sample MR as a validation.

Methods

In the population-representative “Children of 1997” birth cohort, we used multivariable linear regression to assess the adjusted associations of ALT and alkaline phosphatase (ALP) (IU/L) at ~17.5 years with muscle mass (kg) and body fat percentage (%). Genetic variants predicting ALT, ALP and gamma glutamyltransferase (GGT) (100% change in concentration) were applied to fat-free and fat mass (kg) in the UK Biobank (n=~331,000) to obtain unconfounded estimates using MR.

Results

Observationally, ALT was positively associated with muscle mass (0.11, 95% confidence interval (CI) 0.10 to 0.12) and fat percentage (0.15, 95% CI 0.13 to 0.17). ALP was inversely associated with muscle mass (−0.03, 95% CI −0.04 to −0.02) and fat percentage (−0.02, 95% CI −0.03 to −0.01). Using MR, ALT was inversely associated with fat-free mass (−0.41, 95% CI −0.64 to −0.19) and fat mass (−0.58, 95% CI −0.85 to −0.30). ALP was not clearly associated with body composition. GGT was positively associated with fat-free (0.30, 95% CI 0.01 to 0.06) and fat mass (0.41, 95% CI 0.10 to 0.71).

Conclusion

ALT reducing fat-free mass provides a possible pathway for the positive association of ALT with diabetes, and suggests a potential target of intervention.