bluuebunny/crossref_metadata_2025_split huggingface dataset:
A knowledge-based system for personalised lifestyle recommendations: Design and simulation of potential effectiveness on the UK Biobank data
Authors: Cavallo Francesca Romana , Toumazou Christofer 
Published: December 2022

AbstractMobile health applications, which employ wireless technology for healthcare, can aid behaviour change and subsequently improve health outcomes. Mobile health applications have been developed to increase physical activity, but are rarely grounded on behavioural theory and employ simple techniques for personalisation, which has been proven effective in promoting behaviour change. In this work, we propose a theoretically driven and personalised behavioural intervention delivered through an adaptive knowledge-based system. The behavioural system design is guided by the Behavioural Change Wheel and the Capability-Opportunity-Motivation behavioural model. The system exploits the ever-increasing availability of health data from wearable devices, point-of-care tests and consumer genetic tests to issue highly personalised physical activity and sedentary behaviour recommendations. To provide the personalised recommendations, the system firstly classifies the user into one of four diabetes clusters based on their cardiometabolic profile. Secondly, it recommends activity levels based on their genotype and past activity history, and finally, it presents the user with their current risk of developing cardiovascular disease. In addition, leptin, a hormone involved in metabolism, is included as a feedback biosignal to personalise the recommendations further. As a case study, we designed and demonstrated the system on people with type 2 diabetes, since it is a chronic condition often managed through lifestyle changes, such as physical activity increase and sedentary behaviour reduction. We trained and simulated the system using data from diabetic participants of the UK Biobank, a large-scale clinical database, and demonstrate that the system could help increase activity over time. These results warrant a real-life implementation of the system, which we aim to evaluate through human intervention.
Growth Signaling Autonomy in Circulating Tumor Cells Aids Metastatic Seeding
Authors: Sinha Saptarshi , Farfel Alex , Luker Kathryn E. , Parker Barbara A. , Yeung Kay , Luker Gary D. , Ghosh Pradipta 
Published: December 2022

AbstractSelf-sufficiency (autonomy) in growth signaling, the earliest recognized hallmark of cancer, is fueled by the tumor cell’s ability to ‘secrete-and-sense’ growth factors; this translates into cell survival and proliferation that is self-sustained by auto-/paracrine secretion. A Golgi-localized circuitry comprised of two GTPase switches has recently been implicated in the orchestration of growth signaling autonomy. Using breast cancer cells that are either endowed or impaired (by gene editing) in their ability to assemble the circuitry for growth signaling autonomy, here we define the transcriptome, proteome, and phenome of such autonomous state, and unravel its role during cancer progression. We show that autonomy is associated with enhanced molecular programs for stemness, proliferation, and epithelial-mesenchymal plasticity (EMP). Autonomy is both necessary and sufficient for anchorage-independent growth factor-restricted proliferation and resistance to anti-cancer drugs and is required for metastatic progression. Transcriptomic and proteomic studies show that autonomy is associated, with a surprising degree of specificity, to self-sustained EGFR/ErbB signaling. Derivation of a gene expression signature for autonomy revealed that growth signaling autonomy is uniquely induced in circulating tumor cells (CTCs), the harshest phase in the life of tumor cells when it is deprived of biologically available EGF. We also show that autonomy in CTCs tracks therapeutic response and prognosticates outcome. These data support a role for growth signaling autonomy in multiple processes essential for the blood-borne dissemination of human breast cancer.GRAPHIC ABSTRACT:Significance StatementA Golgi-localized molecular circuitry has been recently implicated in the orchestration of secrete-and-sense auto-/paracrine loops that impart self-sufficiency in growth signaling, a.k.a., growth signaling autonomy. Using a transdisciplinary approach, this work shows that growth signaling autonomy is uniquely induced in tumor cells that are in circulation. Circulating tumor cells (CTCs) represent a brutish and risky phase in the lifetime of tumor cells when they are exposed to the immune system and hemodynamic sheer forces, all in the setting of growth factor starvation. Cancer cells appear to rely on the autonomy circuit to survive and enhance their fitness to seed metastases. Autonomy generates the kind of ‘eat-what-you-kill’ entrepreneurial spirit which minimizes the risk of CTCs dying on an otherwise risky journey.
Isobaric crosslinking mass spectrometry technology for studying conformational and structural changes in proteins and complexes
Authors: Luo Jie , Ranish Jeff 
Published: December 2022

AbstractDynamic conformational and structural changes in proteins and protein complexes play a central and ubiquitous role in the regulation of protein function, yet it is very challenging to study these changes, especially for large protein complexes, under physiological conditions. Here we introduce a novel isobaric crosslinker, Qlinker, for studying conformational and structural changes in proteins and protein complexes using quantitative crosslinking mass spectrometry (qCLMS). Qlinkers are small and simple, amine-reactive molecules with an optimal extended distance of ∼10 Å which use MS2 reporter ions for relative quantification of Qlinker-modified peptides derived from different samples. We synthesized the 2-plex Q2linker and showed that the Q2linker can provide quantitative crosslinking data that pinpoints key conformational and structural changes in biosensors, binary and ternary complexes composed of the general transcription factors TBP, TFIIA, and TFIIB, and RNA polymerase II (pol II) complexes.
Drosophilid cuticle pigmentation impacts body temperature
Authors: Freoa Laurent , Chevin Luis-Miguel , Christol Philippe , Méléard Sylvie , Rera Michael , Véber Amandine , Gibert Jean-Michel 
Published: December 2022

AbstractCuticle pigmentation has been clearly demonstrated to impact body temperature for several relatively large species of insects, but it was questioned for small insects. Here we used a thermal camera to assess the impact of drosophilid cuticle pigmentation on body temperature when individuals are exposed to light. We compared mutants of large effects within species (Drosophila melanogaster ebonyandyellowmutants). Then we analyzed the impact of naturally occurring pigmentation variation within species complexes (Drosophila americana/Drosophila novamexicanaandDrosophila yakuba/Drosophila santomea). Finally we analyzed lines ofD. melanogasterwith moderate differences in pigmentation. We found significant differences in temperatures for each of the four pairs we analyzed. The temperature differences appeared to be proportional to the differently pigmented area: betweenDrosophila melanogaster ebonyandyellowmutants or betweenDrosophila americanaandDrosophila novamexicana, for which the whole body is differently pigmented, the difference in temperatures was around 0.6°C ±0.2°C. By contrast, betweenD. yakubaandD. santomeaor betweenDrosophila melanogaster DarkandPalelines, for which only the posterior abdomen is differentially pigmented, we detected a temperature difference of about 0.14°C ±0.10°C. This demonstrates that cuticle pigmentation has ecological implications in drosophilids regarding adaptation to environmental temperature.
Redox-active molecules in bacterial cultivation media produce photocurrent
Authors: Shlosberg Yaniv , Smith Matthew C. , Nasseri Nathan. S. , Morin Emile J. , Limwongyut Jakkarin , Moreland Alex S. , Bazan Guillermo C. , Carlini Andrea S. 
Published: December 2022

AbstractIn recent years, global climate change has urged the importance of developing new clean energy technologies that may replace the combustion of fossil fuels and help to reduce carbon emissions. A promising, yet intrinsically complex solution, is the utilization of bacteria as electron donors in microbial fuel cells (MFCs). In this work, we show that just the cultivation media for bacterial growth, which is based on yeast extract, is sufficient for generating electrical current in a bio-electrochemical cell (BEC). We apply cyclic voltammetry and 2-dimensional fluorescence spectroscopy to identify redox active molecules such as NADH, NAD+, and flavines that may play key roles in electron donation. Finally, we show that upon illumination, current production is enhanced 2-fold. This photocurrent is generated by a variety of metabolites capable of photochemical reduction, enabling them to donate electrons at the anode of the BEC. Future investigations into the role of culture media versus that of living cells in MFCs may aid in reducing overall production and maintenance costs, and enhance power output performance.
Sharing Massive Biomedical Data at Magnitudes Lower Bandwidth Using Implicit Neural Function
Authors: Yang Runzhao , Xiao Tingxiong , Cheng Yuxiao , Li Anan , Qu Jinyuan , Liang Rui , Bao Shengda , Wang Xiaofeng , Wang Jue , Suo Jinli , Luo Qingming , Dai Qionghai 
Published: December 2022

ABSTRACTEfficient storage and sharing of massive biomedical data would open up their wide accessibility to different institutions and disciplines. However, compressors tailored for natural photos/videos are rapidly limited for biomedical data, while emerging deep learning based methods demand huge training data and are difficult to generalize. Here we propose to conduct Biomedical data compRession with Implicit nEural Function (BRIEF) by representing the original data with compact neural networks, which are data specific and thus have no generalization issues. Benefiting from the strong representation capability of implicit neural function, BRIEF achieves 2 ∼ 3 orders of magnitude compression on diverse biomedical data at significantly higher fidelity than existing techniques. Besides, BRIEF is of consistent performance across the whole data volume, supports customized spatially-varying fidelity. BRIEF’s multi-fold advantageous features also serve reliable downstream tasks at low bandwidth. Our approach will facilitate low-bandwidth data sharing, and promote collaboration and progress in the biomedical field.
“It reminds me and motivates me”: Human-centered design and implementation of an interactive, SMS-based digital intervention to improve early retention on antiretroviral therapy: usability and acceptability among new initiates in a high-volume, public clinic in Malawi
Authors: Huwa Jacqueline , Tweya Hannock , Mureithi Maryanne , Oni Femi , Chintedza Joseph , Chiwaya Geldert , Waweru Evelyn , Kudzala Aubrey , Wasunna Beatrice , Ndhlovu Dumisani , Bisani Pachawo , Feldacker Caryl 
Published: December 2022

AbstractBackgroundEarly retention of people living with HIV (PLHIV) in antiretroviral therapy (ART) programs is critical to improve individual clinical outcomes and viral load suppression. Although many mobile health (mHealth) interventions aim to improve retention in care, there is still lack of evidence on mHealth success or failure, including from patient’s perspectives. We describe the human-centered design (HCD) process and assess patient usability and acceptability of a two-way texting (2wT) intervention to improve early retention among new ART initiates at Lighthouse Trust clinic in Lilongwe, Malawi.MethodsAn iterative HCD approach focused on patient and provider users’ needs, incorporating feedback from multidisciplinary teams to adapt 2wT for the local, public clinic context. We present mixed-methods usability and acceptability results from 100 participants, 50 at 3-months and 50 at 6-months, post 2wT enrollment, and observations of these same patients completing core tasks of the 2wT system.ResultsAmong the 100 usability respondents, 95% were satisfied with visit reminders, and 88% would recommend reminders and motivational messages to friends; however, 17% were worried about confidentiality. In observation of participant task completion, 94% were able to successfully confirm visit attendance and 73% could request appointment date change. More participants in 4-6 months group completed tasks correctly compared to 1-3 months group, although not significantly different (78% vs. 66%, p=0.181). Qualitative results were overwhelmingly positive, but patients did note confusion with transfer reporting and concern that 2wT would not reach patients without mobile phones or with lower literacy.ConclusionThe 2wT app for early ART retention appears highly usable and acceptable, hopefully creating a solid foundation for lifelong engagement in care. The HCD approach put the local team central in this process, ensuring that both patients’ and Lighthouse’s priorities, policies, and practices were forefront in 2wT optimization, raising the likelihood of 2wT success in other routine program contexts.
Identification of Spatial Proteomic Signatures of Colon Tumor Metastasis: A Digital Spatial Profiling Approach
Authors: Levy Joshua J. , Zavras John P. , Veziroglu Eren M. , Nasir-Moin Mustafa , Kolling Fred W. , Christensen Brock C. , Salas Lucas A. , Barney Rachael E. , Palisoul Scott M. , Ren Bing , Liu Xiaoying , Kerr Darcy A. , Pointer Kelli B. , Tsongalis Gregory J. , Vaickus Louis J. 
Published: December 2022

AbstractOver 150,000 Americans are diagnosed with colorectal cancer (CRC) every year, and annually over 50,000 individuals will die from CRC, necessitating improvements in screening, prognostication, disease management, and therapeutic options. CRC tumors are removed en bloc with surrounding vasculature and lymphatics. Examination of regional lymph nodes at the time of surgical resection is essential for prognostication. Developing alternative approaches to indirectly assess recurrence risk would have utility in cases where lymph node yield is incomplete or inadequate. Spatially dependent, immune cell-specific (e.g., Tumor Infiltrating Lymphocytes– TILs), proteomic, and transcriptomic expression patterns inside and around the tumor - the tumor immune microenvironment (TIME) - can predict nodal/distant metastasis and probe the coordinated immune response from the primary tumor site. The comprehensive characterization of TILs and other immune infiltrates is possible using highly multiplexed spatial omics technologies, such as the GeoMX Digital Spatial Profiler (DSP). In this study, machine learning and differential co-expression analyses helped identify biomarkers from DSP-assayed protein expression patterns inside, at the invasive margin, and away from the tumor, associated with extracellular matrix remodeling (e.g., GZMB, fibronectin), immune suppression (e.g., FOXP3), exhaustion and cytotoxicity (e.g., CD8), PD-L1 expressing dendritic cells, neutrophil proliferation, amongst other concomitant alterations. Further investigation of these biomarkers may reveal independent risk factors of CRC metastasis that can be formulated into low-cost, widely available assays.
Molecular methods for diagnosis of monkeypox: A mini-review
Authors: de Oliveira Thomasi Rodrigo Michelini , Silva Correa Thais da , do Carmo Dalise Silva , Rodrigues Déborah Fernandes , da Silva Correa Luiz Vinicius , Xavier Sandra Rodrigues , Silva Liria Souza , da Silva Jonatas Oliveira , Santos Michelli dos , Silva Dantas Alessandra da , da Paz Mariana Campos , Chávez Fumagalli Miguel Angel , Giunchetti Rodolfo Cordeiro , Ferraz Coelho Eduardo Antônio , Machado Juliana Martins , Galdino Alexsandro Sobreira 
Published: December 2022

ABSTRACTBackgroundMonkeypox is a global public health issue caused by the monkeypox virus (MPXV), a virus belonging to the Orthopoxvirus genus. As of October 28 2022, a total of 77,115 laboratory-confirmed cases and 3,610 probable cases, including 36 deaths, were reported, with 9,070 cases reported in Brazil, the second most affected country. The need to develop national technologies for the rapid diagnosis of emerging diseases for mass testing of the population is evident, as observed in the current SARS-CoV-2 pandemic. With that in mind, this article provides an overview of current methods, techniques, and their applications in the molecular detection of monkeypox.MethodsThe relevant documents or papers covered in this study were selected by a search in international bibliographic databases. The search terms used in the databases were aimed at summarizing existing knowledge on molecular diagnostic methods, such as: monkeypox; MPX, MPXV, qPCR, PCR, PCR-ELISA, and Diagnosis and Detection searched separately or together using the Boolean operator “AND” either in the title or abstract. The searches took place in September 2022, and the corresponding articles were selected between 2012 and 2022.ResultsWe found 256 documents in total and twelve studies addressing the molecular diagnosis of monkeypox were classified as possible sources for this review.ConclusionThis paper presents new perspectives and an overview of current methods, technologies, and applications in the molecular diagnosis of monkeypox. It is evident there is a pressing need to develop national technologies for the rapid diagnosis of emerging diseases for mass testing of the population. It is extremely important to have national detection kits with greater diagnostic capacity to assist in developing effective public policies in countries affected by this disease.
Prior expectation enhances sensorimotor behavior by modulating population tuning and subspace activity in the sensory cortex
Authors: Park JeongJun , Kim Seolmin , Kim HyungGoo R. , Lee Joonyeol 
Published: December 2022

AbstractPrior knowledge facilitates our perception and goal-directed behaviors in the dynamic world, particularly when sensory input is lacking or noisy. However, the neural mechanisms underlying the improvement in sensorimotor behaviors by prior expectations remain unknown. In this study, we examine the neural activity in the middle temporal (MT) area of visual cortex while monkeys perform a smooth pursuit eye movement task with prior expectation of the visual target’s motion direction. Prior expectations discriminately reduce the MT neural responses depending on their preferred directions, only when the sensory evidence is weak. This response reduction effectively sharpens neural population direction tuning. Simulations with a realistic MT population demonstrate that sharpening the tuning explains both the biases and variabilities in smooth pursuit, thus suggesting that neural computations in the sensory area alone can underpin the integration of prior knowledge and sensory evidence. State-space analysis further supports this by revealing neural signals of prior expectation in the MT population activity that correlate with behavioral changes.
Stimulus information guides the emergence of behavior related signals in primary somatosensory cortex during learning
Authors: Panniello Mariangela , Gillon Colleen J , Maffulli Roberto , Celotto Marco , Panzeri Stefano , Richards Blake A , Kohl Michael M 
Published: December 2022

ABSTRACTCortical neurons in primary sensory cortex carry not only sensory but also behavior-related information. However, it remains unclear how these types of information emerge and are integrated with one another over learning and what the relative contribution of activity in individual cells versus neuronal populations is in this process. Current evidence supports two opposing views of learning-related changes: 1) sensory information increases in primary cortex or 2) sensory information remains stable in primary cortex but its readout efficiency in association cortices increases. Here, we investigate these questions in primary sensory cortex during learning of a sensory task. Over the course of weeks, we imaged neuronal activity at different depths within layers 2 and 3 of the mouse vibrissal primary somatosensory cortex (vS1) before, during, and after training on a whisker-based object-localization task. We leveraged information theoretical analysis to quantify stimulus and behavior-related information in vS1 and estimate how much neural activity encoding sensory information is used to inform perceptual choices as sensory learning progresses. We also quantified the extent to which these types of information are supported by an individual neuron or population code. We found that, while sensory information rises progressively from the start of training, choice information is only present in the final stages of learning and is increasingly supported by a population code. Moreover, we demonstrate that not only the increase in available information, but also a more efficient readout of such information in primary sensory cortex mediate sensory learning. Together, our results highlight the importance of primary cortical neurons in perceptual learning.
Behavioral encoding across timescales by region-specific dopamine dynamics
Authors: Jørgensen Søren H. , Ejdrup Aske L. , Lycas Matthew D. , Posselt Leonie P. , Madsen Kenneth L. , Tian Lin , Dreyer Jakob K. , Herborg Freja , Sørensen Andreas T. , Gether Ulrik 
Published: December 2022

AbstractThe dorsal (DS) and ventral striatum (VS) receive dopaminergic projections that control motor functions and reward-related behavior. It remains poorly understood how dopamine release dynamics across different temporal scales in these regions are coupled to behavioral outcomes. Here, we employ the dopamine sensor dLight1.3b together with multi-region fiber photometry and machine learning-based analysis to decode dopamine dynamics across striatum during self-paced exploratory behavior in mice. Our data show a striking coordination of rapidly fluctuating signal in the DS, carrying information across dopamine levels, with a slower signal in the VS, consisting mainly of slow-paced transients. Importantly, these release dynamics correlated with discrete behavioral motifs, such as turns, running and grooming on a subsecond-to-minutes time scale. Disruption of dopamine dynamics with cocaine caused randomization of action selection sequencing and disturbance of DS-VS coordination. The data suggest that distinct dopamine dynamics of DS and VS jointly encode behavioral sequences during unconstrained activity with DS modulating the stringing together of actions and VS the signal to initiate and sustain the selected action.Significance StatementNew genetically encoded dopamine sensors offer unprecedented temporal resolution for measurement of dopamine release dynamics across different brain regions over extended periods. In this study, we use the dopamine sensor dLight1.3b to decipher the role of dopamine release dynamics in the dorsal (DS) and ventral striatum (VS) of mice during simple, self-paced exploratory behavior. By AI-based splitting of behavioral kinematics into individual motifs, we link differential but highly cooperative dopamine release dynamics of DS and VS with movements on a subsecond-to-minutes time scales. In addition to coupling region-specific dopamine dynamics to behavioral sequences, our study demonstrates the strength of a machine learning-based data analysis pipeline that can be readily applied to other neurotransmitters for which genetically encoded biosensors are available.