bluuebunny/crossref_metadata_2025 huggingface dataset:
Axi-Stack: a method for manufacturing freeform air-silica optical fibre
Authors: Ross Calum A. , Harrington Kerrianne , Mears Robbie , Stone James M. , Birks Tim A. , Thomson Robert R.
Published: December 2023

We present a method with potential for fabricating freeform air-silica optical fibre preforms which is free from the stacking constraints associated with conventional stack-and-draw. The method, termed Axi-Stack, is enabled by the precision machining of short cross-sectional preform discs by ultrafast laser assisted etching; a laser-based microfabrication technique which facilitates near arbitrary shaping of the preform structure. Several preform discs are stacked axially and fused together via ultrafast laser welding to construct the preform, which can be drawn to fibre using conventional methods. To illustrate the Axi-Stack process, we detail the fabrication of a 30 cm long solid-core photonic crystal fibre preform with a square lattice of cladding holes and characterise fibre drawn from it.
7.56-W continuous-wave Pr3+-based green laser via managing thermally induced effects
Authors: Zhang Shouyan , Wang Shuxian , Lian Gang , Wang Zhengping , Yu Haohai , Zhang Huaijin
Published: December 2023

Blue-laser-diode-pumped Pr3+-based continuous-wave (CW) green lasers have aroused growing research interest in developing optoelectronic applications and deep ultraviolet laser sources due to their simple and compact structural design. However, the obstacle of thermally induced effects limits the available output power of Pr3+-based green lasers. Herein, combined with the theoretical analysis and experimental feedback, we effectively adjust the heat distribution inside the Pr3+:LiYF4 gain crystal by optimizing the crystal dimension and doping concentration. The excellent mode matching between the pump and green lasers is achieved under the consideration of thermally induced effects, yielding a maximum CW output power of 7.56 W. To the best of our knowledge, this is the largest output power of Pr3+-based CW green lasers so far. Moreover, the obtained green laser demonstrates excellent output stability (RMS = 1.27%) and beam quality (M2 = 1.30 × 1.12) under the lasing operation state with the maximum output power. We hope that this study can provide a feasible paradigm for developing blue-laser-diode-pumped visible lasers, especially for high-power lasers.
High-efficiency, single-stage tunable optical parametric amplifier for visible photocathode applications
Authors: Lu Brittany , Shiri Abbas , Wernsing Keith , Carbajo Sergio
Published: December 2023

We present a single-stage optical parametric amplifier (OPA) with an average conversion efficiency up to 38%, tunable between 1.01 and 1.18 µm. The OPA seed is produced by a gain-managed nonlinear fiber amplifier. Numerical modeling of the seed pulse generation shows a linear chirp, a smoothly broadened redshifted spectrum, and a high spectral energy density. When up-converted to the visible through second-harmonic generation, the signal pulses are suitable for visible photocathode excitation.
Identification of dynamical changes of rabies transmission under quarantine: Community-based measures towards rabies elimination
Authors: Rysava Kristyna , Tildesley Michael J.
Published: December 2023

Quarantine has been long used as a public health response to emerging infectious diseases, particularly at the onset of an epidemic when the infected proportion of a population remains identifiable and logistically tractable. In theory, the same logic should apply to low-incidence infections; however, the application and impact of quarantine in low prevalence settings appears less common and lacks a formal analysis. Here, we present a quantitative framework using a series of progressively more biologically realistic models of canine rabies in domestic dogs and from dogs to humans, a suitable example system to characterize dynamical changes under varying levels of dog quarantine. We explicitly incorporate health-seeking behaviour data to inform the modelling of contact-tracing and exclusion of rabies suspect and probable dogs that can be identified through bite-histories of patients presenting at anti-rabies clinics. We find that a temporary quarantine of rabies suspect and probable dogs provides a powerful tool to curtail rabies transmission, especially in settings where optimal vaccination coverage is yet to be achieved, providing a critical stopgap to reduce the number of human and animal deaths due to rabid bites. We conclude that whilst comprehensive measures including sensitive surveillance and large-scale vaccination of dogs will be required to achieve disease elimination and sustained freedom given the persistent risk of rabies re-introductions, quarantine offers a low-cost community driven solution to intersectoral health burden.
NOAA fisheries research geared towards climate-ready living marine resource management in the northeast United States
Authors: Saba Vincent , Borggaard Diane , Caracappa Joseph C. , Chambers R. Christopher , Clay Patricia M. , Colburn Lisa L. , Deroba Jonathan , DePiper Geret , du Pontavice Hubert , Fratantoni Paula , Ferguson Marianne , Gaichas Sarah , Hayes Sean , Hyde Kimberly , Johnson Michael , Kocik John , Keane Ellen , Kircheis Dan , Large Scott , Lipsky Andrew , Lucey Sean , Mercer Anna , Meseck Shannon , Miller Timothy J. , Morse Ryan , Orphanides Christopher , Reichert-Nguyen Julie , Richardson David , Smith Jeff , Vogel Ronald , Vogt Bruce , Wikfors Gary
Published: December 2023

Climate change can alter marine ecosystems through changes in ocean temperature, acidification, circulation, and productivity. Over the last decade, the United States northeast continental shelf (U.S. NES) has warmed faster than any other marine ecosystem in the country and is among the fastest warming regions of the global ocean. Many living marine resources in the U.S. NES ranging from recreational and commercial fish stocks to protected species have shifted their distribution in response to ocean warming. The National Oceanic and Atmospheric Administration’s National Marine Fisheries Service (NOAA Fisheries) is responsible for the assessment, protection, and sustainable use of the nation’s living marine resources. In the U.S. NES, NOAA Fisheries has made substantial progress on climate research related to fish, fisheries, and protected species. However, more research is needed to help inform tactical management decisions with the goal of climate-ready living marine resource management. This is a major challenge because the observed physical and biological changes are unprecedented, and the majority of marine species assessments and management decisions do not utilize environmental data. Here we review the research accomplishments and key needs for NOAA Fisheries in the U.S. NES in the context of climate change and living marine resource management. Key research needs and products are: 1) Infrastructure with continued and enhanced ocean surveys that includes cooperative research with the fishing industry and other NOAA line offices and partners; 2) Tracking and projecting change, and understanding mechanisms including state of the ecosystem reporting, improved regional ocean and ecosystem hindcasts, forecasts, and projections, and continued process-based laboratory and field studies, 3) climate-informed management, including stock assessments that account for climate where possible, translation of changing species distributions into spatial management, climate vulnerability assessment and scenario planning, ecosystem-based management, management strategy evaluations, and increased multidisciplinary science that includes economic and social indicators.
Telehealth and digital health innovations: A mixed landscape of access
Authors: Phuong Jimmy , Ordóñez Patricia , Cao Jerry , Moukheiber Mira , Moukheiber Lama , Caspi Anat , Swenor Bonnielin K. , Naawu David Kojo N. , Mankoff Jennifer
Published: December 2023

In the wake of emergent natural and anthropogenic disasters, telehealth presents opportunities to improve access to healthcare when physical access is not possible. Yet, since the beginning of the COVID pandemic, lessons learned reveal that various populations in the United States do not or cannot adopt telehealth due to inequitable access. We explored the Digital Determinants of Health (DDoHs) for telehealth, characterizing the role of accessibility, broadband connectivity and electrical grids, and patient intersectionality. In addition to its role as an existing Social Determinant of Health, Policies and Laws directly and indirectly affect these DDoHs, making access more complex for marginalized populations. Digital systems lack the flexibility, accessibility, and usability to inclusively provide the essential services patients need in telehealth. We propose the following recommendations: (1) design technology and systems using accessibility and value sensitive design principles; (2) support a range of technologies and settings; (3) support multiple and diverse users; and (4) support clear paths for repair when technical systems fail to meet users’ needs. Addressing these requires change not only from providers but also from the institutions providing these systems.
Dual functioning by the PhoR sensor is a key determinant to Mycobacterium tuberculosis virulence
Authors: Singh Prabhat Ranjan , Goar Harsh , Paul Partha , Mehta Khushboo , Bamniya Bhanwar , Vijjamarri Anil Kumar , Bansal Roohi , Khan Hina , Karthikeyan Subramanian , Sarkar Dibyendu
Published: December 2023

PhoP-PhoR, one of the 12 two-component systems (TCSs) that empower M. tuberculosis to sense and adapt to diverse environmental conditions, remains essential for virulence, and therefore, represents a major target to develop novel anti-TB therapies. Although both PhoP and PhoR have been structurally characterized, the signal(s) that this TCS responds to remains unknown. Here, we show that PhoR is a sensor of acidic pH/high salt conditions, which subsequently activate PhoP via phosphorylation. In keeping with this, transcriptomic data uncover that acidic pH- inducible expression of PhoP regulon is significantly inhibited in a PhoR-deleted M. tuberculosis. Strikingly, a set of PhoP regulon genes displayed a low pH-dependent activation even in the absence of PhoR, suggesting the presence of non-canonical mechanism(s) of PhoP activation. Using genome-wide interaction-based screening coupled with phosphorylation assays, we identify a non-canonical mechanism of PhoP phosphorylation by the sensor kinase PrrB. To investigate how level of P~PhoP is regulated, we discovered that in addition to its kinase activity PhoR functions as a phosphatase of P~PhoP. Our subsequent results identify the motif/residues responsible for kinase/phosphatase dual functioning of PhoR. Collectively, these results uncover that contrasting kinase and phosphatase functions of PhoR determine the homeostatic mechanism of regulation of intra-mycobacterial P~PhoP which controls the final output of the PhoP regulon. Together, these results connect PhoR to pH-dependent activation of PhoP with downstream functioning of the regulator. Thus, PhoR plays a central role in mycobacterial adaptation to low pH conditions within the host macrophage phagosome, and a PhoR-deleted M. tuberculosis remains significantly attenuated in macrophages and animal models.
Clinical readiness for essential maternal and child health services in Kenya: A cross-sectional survey
Authors: Hagey Jill M. , Oketch Sandra Y. , Weber Jeremy M. , Pieper Carl F. , Huchko Megan J.
Published: December 2023

High rates of maternal and neonatal morbidity and mortality in Kenya may be influenced by provider training and knowledge in emergency obstetric and neonatal care in addition to availability of supplies necessary for this care. While post-abortion care is a key aspect of life-saving maternal health care, no validated questionnaires have been published on provider clinical knowledge in this arena. Our aim was to determine provider knowledge of maternal-child health (MCH) emergencies (post-abortion care, pre-eclampsia, postpartum hemorrhage, neonatal resuscitation) and determine factors associated with clinical knowledge. Our secondary aim was to pilot a case-based questionnaire on post-abortion care. We conducted a cross-sectional survey of providers at health facilities in western Kenya providing maternity services. Providers estimated facility capacity through perceived availability of both general and specialized supplies. Providers reported training on the MCH topics and completed case-based questions to assess clinical knowledge. Knowledge was compared between topics using a linear mixed model. Multivariable models identified variables associated with scores by topic. 132 providers at 37 facilities were interviewed. All facilities had access to general supplies at least sometime while specialized supplies were available less frequently. While only 56.8% of providers reported training on post-abortion care, more than 80% reported training on pre-eclampsia, postpartum hemorrhage, and neonatal resuscitation. Providers’ clinical knowledge across all topics was low (mean score of 63.3%), with significant differences in scores by topic area. Despite less formal training in the subject area, providers answered 71.6% (SD 16.7%) questions correctly on post-abortion care. Gaps in supply availability, training, and clinical knowledge on MCH emergencies exist. Increasing training on MCH topics may decrease pregnancy and postpartum complications. Further, validated tools to assess knowledge in post-abortion care should be created, particularly in sub-Saharan Africa where legal restrictions on abortion services exist and many abortions are performed in unsafe settings.
Potential implications of shortened rotation length for forest birds, bryophytes, lichens and vascular plants: An example from southern Swedish production forests
Authors: Petersson Lisa , Lariviere Delphine , Holmström Emma , Lindbladh Matts , Felton Adam
Published: December 2023

The rotation lengths of intensively managed production forests may be altered to achieve a variety of goals, with correspondingly implications for biodiversity. Here we consider the potential implications of shortened rotation times for biodiversity in planted monocultures of the two most common production tree species in Sweden, Scots pine (Pinus sylvestris) and Norway spruce (Picea abies). To do so we surveyed bird, bryophyte, epiphytic lichen and vascular plant diversity in 80 and 55-year-old stands; stand ages which approximate present-day and potential future rotation lengths in this region respectively. We found clear differences in the species communities of the 55 compared to the 80-year-old stands for both understory species and epiphytes, but not for birds. Nevertheless, bird species richness was still highest in the 80-year-old Norway spruce dominated stands. Dead wood amount was also highest the 80-year-old Norway spruce stands. Highest species richness of epiphytic lichens was found in 80-year-old Scots pine stands. However, 55-year-old Scots pine stands had a higher understory species richness and diversity than the older Scots pine stands, including a larger number of open land species. The 80-year-old forest stands examined may be considered old with respect to production forest rotation lengths in Sweden but are relatively young when comparing stand ages of unmanaged natural forest stands. Nevertheless, our results indicate that shortening the rotation time of Scots pine and Norway spruce, in this part of Sweden from 80 to 55 years, could have important consequences for forest biodiversity. These consequences are primarily inferred from the likely implications from shortened rotations for lichens community composition and diversity in both Norway spruce and Scots pine stands, as well as impacts on understory plant species in Norway spruce stands.
AAAKB: A manually curated database for tracking and predicting genes of Abdominal aortic aneurysm (AAA)
Authors: Yao Di , Mei Shuyuan , Tang Wangyang , Xu Xingyu , Lu Qiulun , Shi Zhiguang
Published: December 2023

Abdominal aortic aneurysm (AAA), an extremely dangerous vascular disease with high mortality, causes massive internal bleeding due to aneurysm rupture. To boost the research on AAA, efforts should be taken to organize and link the information about AAA-related genes and their functions. Currently, most researchers screen through genetic databases manually, which is cumbersome and time-consuming. Here, we developed “AAAKB” a manually curated knowledgebase containing genes, SNPs and pathways associated with AAA. In order to facilitate researchers to further explore the mechanism network of AAA, AAAKB provides predicted genes that are potentially associated with AAA. The prediction is based on the protein interaction information of genes collected in the database, and the random forest algorithm (RF) is used to build the prediction model. Some of these predicted genes are differentially expressed in patients with AAA, and some have been reported to play a role in other cardiovascular diseases, illustrating the utility of the knowledgebase in predicting novel genes. Also, AAAKB integrates a protein interaction visualization tool to quickly determine the shortest paths between target proteins. As the first knowledgebase to provide a comprehensive catalog of AAA-related genes, AAAKB will be an ideal research platform for AAA. Database URL: http://www.lqlgroup.cn:3838/AAAKB/.
Content comparison of unmet needs self-report measures for lymphoma cancer survivors: A systematic review
Authors: Boland Vanessa , Drury Amanda , Brady Anne-Marie
Published: December 2023

Purpose

The increasing recognition of the complex impacts of a cancer diagnosis and its treatment has led to efforts to develop instruments to reflect survivors’ needs accurately. However, evidence regarding the content and quality of instruments used to evaluate the unmet needs of lymphoma survivors is lacking. This review aimed to evaluate the psychometric properties and comprehensiveness of available self-report instruments to assess unmet needs and quality of life with adult lymphoma survivors.

Methods

A systematic search of five databases (CINAHL, EMBASE, Medline, PsycInfo and Scopus) was conducted to identify instruments measuring unmet needs or quality of life outcomes. Original articles reporting the instrument’s validation or development via citation screening were retrieved and screened against eligibility criteria. An appraisal of the instrument’s measurement properties was conducted, guided by the COSMIN methodology and reported in accordance with PRISMA guidelines. A content comparison using the Supportive Care in Cancer Framework was performed.

Results

Twelve instruments met the inclusion criteria; only one was explicitly developed for lymphoma (Functional Assessment of Cancer Therapy–Lymphoma). Four instruments focused on the construct of need, and eight focused on quality of life. The psychometric data in the published literature is not comprehensive; there is heterogeneity in their development, content and quality. No included instrument was examined for all COSMIN measurement properties, and methodological quality was variable; all instruments measured at least four domains of need. The emotional domain was reviewed by all instruments (n = 12), and the spiritual and informational domains received the least focus (n = 4 each).

Conclusion

This review provides a platform for instrument comparison, with suggestions for important factors to consider in systematically selecting unmet needs and quality of life self-report measures for adult lymphoma survivors. Considering the various discrepancies and limitations of the available instruments, using more than one instrument is recommended. In selecting measurement instruments, researchers should consider research objectives, study design, psychometric properties and the pros and cons of using more than one measure. Evaluating the participant burden and feasibility of completing the selected instrument is important for lymphoma survivors, a group burdened by cancer-related fatigue and cognitive impairment.
The impact of digital economy on high-quality economic development: Research based on the consumption expansion
Authors: Li Xiaoxuan , Wu Qi
Published: December 2023

Studies have found that the digital economy plays a positive role in promoting high-quality economic development. Meanwhile, the digital industrialization and industrial digitalization have given rise to new demands and supply modes of consumption. It is necessary to analyze the role of consumption expansion in the impact of digital economy on high-quality economic development. Based on Chinese provincial panel data, we first applied the entropy weight method to construct the digital economy index and the high-quality economic development index. And on this basis, it was verified that the digital economy can positively promote the high-quality development of the inverted U-shaped structural economy. Then we separately used the mediation and the threshold effect models to analyze the role of consumption expansion in empowering high-quality development in the digital economy. Regional heterogeneity was further taken into account. The results dedicate that consumer demand and the digital economy have a partial or complete mediating effect. The promotion of high-quality development by the digital economy can be affected by the threshold of consumption expansion, which is manifested in the marginal incremental effect due to the growth of consumption supply. On the contrary, the growth of consumer demand has led to the inverted U-shape of the digital economy to promote high-quality economic development. In the heterogeneity analysis, the threshold effect also varied greatly. This research enriches the theoretical achievements and reveals the impact of consumption expansion on the digital economy affecting the high-quality development, which may provide certain reference for other countries and regions.
Epidemiology and burden of Severe Acute Respiratory Infections (SARI) in the aftermath of COVID-19 pandemic: A prospective sentinel surveillance study in a Tunisian Medical ICU, 2022/2023
Authors: Boussarsar Mohamed , Ennouri Emna , Habbachi Naima , Bouguezzi Nabil , Meddeb Khaoula , Gallas Salma , Hafdhi Malek , Zghidi Marwa , Toumi Radhouane , Ben Saida Imen , Abid Salma , Boutiba-Ben Boubaker Ilhem , Maazaoui Latifa , El Ghord Hakim , Gzara Ahlem , Yazidi Rihab , Ben Salah Afif
Published: December 2023

Background

Severe Acute Respiratory Infections (SARI) caused by influenza and other respiratory viruses pose significant global health challenges, and the COVID-19 pandemic has further strained healthcare systems. As the focus shifts from the pandemic to other respiratory infections, assessing the epidemiology and burden of SARI is crucial for healthcare planning and resource allocation. Aim: to understand the impact of the post-pandemic period on the epidemiology of SARI cases, clinical outcomes, and healthcare resource utilization in Tunisia.

Methods

This is a prospective study conducted in a Tunisian MICU part of a national sentinel surveillance system, focusing on enhanced SARI surveillance. SARI cases from week 39/2022, 26 September to week 19/2023, 13 May were included, according to a standardized case definition. Samples were collected for virological RT-PCR testing, and an electronic system ensured standardized and accurate data collection. Descriptive statistics were performed to assess epidemiology, trends, and outcomes of SARI cases, and univariate/multivariate analyses to assess factors associated with mortality.

Results

Among 312 MICU patients, 164 SARI cases were identified during the study period. 64(39%) RT-PCR were returned positive for at least one pathogen, with influenza A and B strains accounting for 20.7% of cases at the early stages of the influenza season. The MICU experienced a significant peak in admissions during weeks 1-11/2023, leading to resource mobilization and the creation of a surge unit. SARI cases utilized 1664/3120 of the MICU-stay days and required 1157 mechanical ventilation days. The overall mortality rate among SARI cases was 22.6%. Age, non-COPD, and ARDS were identified as independent predictors of mortality.

Conclusions

The present study identified a relatively high rate of SARI cases, with 39% positivity for at least one respiratory virus, with influenza A and B strains occurring predominantly during the early stages of the influenza season. The findings shed light on the considerable resource utilization and mortality associated with these infections, underscoring the urgency for proactive management and efficient resource allocation strategies.
Numbers of wildlife fatalities at renewable energy facilities in a targeted development region
Authors: Conkling Tara J. , Fesnock Amy L. , Katzner Todd E.
Published: December 2023

Increased interest in renewable energy has fostered development of wind and solar energy facilities globally. However, energy development sometimes has negative environmental impacts, such as wildlife fatalities. Efforts by regional land managers to balance energy potential while minimizing fatality risk currently rely on datasets that are aggregated at continental, but not regional scales, that focus on single species, or that implement meta-analyses that inappropriately use inferential statistics. We compiled and summarized fatality data from 87 reports for solar and wind facilities in the Mojave and Sonoran Deserts region of southern California within the Desert Renewable Energy Conservation Plan area. Our goal was to evaluate potential temporal and guild-specific patterns in fatalities, especially for priority species of conservation concern. We also aimed to provide a perspective on approaches interpreting these types of data, given inherent limitations in how they were collected. Mourning doves (Zenaida macroura), Chukar (Alectoris chukar) and California Quail (Callipepla californica), and passerines (Passeriformes), accounted for the most commonly reported fatalities. However, our aggregated count data were derived from raw, uncorrected totals, and thus reflect an absolute minimum number of fatalities for the monitored period. Additionally, patterns in the raw data suggested that many species commonly documented as fatalities (e.g., waterbirds and other nocturnal migrants, bats) are rarely counted during typical pre-construction use surveys. This may explain the more commonly observed mismatch between pre-construction risk assessment and actual fatalities. Our work may serve to guide design of future scientific research to address temporal and spatial patterns in fatalities and to apply rigorous guild-specific survey methodologies to estimate populations at risk from renewable energy development.
Differential activation of mouse and human Panx1 channel variants
Authors: Cibelli Antonio , Dohare Preeti , Spray David C. , Scemes Eliana
Published: December 2023

Pannexins are ubiquitously expressed in human and mouse tissues. Pannexin 1 (Panx1), the most thoroughly characterized member of this family, forms plasmalemmal membrane channels permeable to relatively large molecules, such as ATP. Although human and mouse Panx1 amino acid sequences are conserved in the presently known regulatory sites involved in trafficking and modulation of the channel, differences are reported in the N- and C-termini of the protein, and the mechanisms of channel activation by different stimuli remain controversial. Here we used a neuroblastoma cell line to study the activation properties of endogenous mPanx1 and exogenously expressed hPanx1. Dye uptake and electrophysiological recordings revealed that in contrast to mouse Panx1, the human ortholog is insensitive to stimulation with high extracellular [K+] but responds similarly to activation of the purinergic P2X7 receptor. The two most frequent Panx1 polymorphisms found in the human population, Q5H (rs1138800) and E390D (rs74549886), exogenously expressed in Panx1-null N2a cells revealed that regarding P2X7 receptor mediated Panx1 activation, the Q5H mutant is a gain of function whereas the E390D mutant is a loss of function variant. Collectively, we demonstrate differences in the activation between human and mouse Panx1 orthologs and suggest that these differences may have translational implications for studies where Panx1 has been shown to have significant impact.
Long-term care transitions during a global pandemic: Planning and decision-making of residents, care partners, and health professionals in Ontario, Canada
Authors: Carbone Sarah , Berta Whitney , Law Susan , Kuluski Kerry
Published: December 2023

The COVID-19 pandemic appears to have shifted the care trajectories of many residents and care partners in Ontario who considered leaving LTC to live in the community for a portion or the duration of the pandemic. This type of care transition–from LTC to home care–was highly uncommon prior to the pandemic, therefore we know relatively little about the planning and decision-making involved. The aim of this study was to describe who was involved in LTC to home care transitions in Ontario during the COVID-19 pandemic, to what extent, and the factors that guided their decision-making. A qualitative description study involving semi-structured interviews with 32 residents, care partners and health professionals was conducted. Transition decisions were largely made by care partners, with varied input from residents or health professionals. Stakeholders considered seven factors, previously identified in a scoping review, when making their transition decisions: (a) institutional priorities and requirements; (b) resources; (c) knowledge; (d) risk; (e) group structure and dynamic; (f) health and support needs; and (g) personality preferences and beliefs. Participants’ emotional responses to the pandemic also influenced the perceived need to pursue a care transition. The findings of this research provide insights towards the planning required to support LTC to home care transitions, and the many challenges that arise during decision-making.
Untangling the effects of multiple exposures with a common reference group in an epidemiologic study: A practical revisit
Authors: Fontaine Robert E. , He Yulei , Zhu Bao-Ping
Published: December 2023

When assessing multiple exposures in epidemiologic studies, epidemiologists often use multivariable regression models with main effects only to control for confounding. This method can mask the true effects of individual exposures, potentially leading to wrong conclusions. We revisited a simple, practical, and often overlooked approach to untangle effects of the exposures of interest, in which the combinations of all levels of the exposures of interest are recoded into a single, multicategory variable. One category, usually the absence of all exposures of interest, is selected as the common reference group (CRG). All other categories representing individual and joint exposures are then compared to the CRG using indicator variables in a regression model or in a 2×2 contingency table analysis. Using real data examples, we showed that using the CRG analysis results in estimates of individual and joint effects that are mutually comparable and free of each other’s confounding effects, yielding a clear, accurate, intuitive, and simple summarization of epidemiologic study findings involving multiple exposures of interest.
An agent-based nested model integrating within-host and between-host mechanisms to predict an epidemic
Authors: Tatsukawa Yuichi , Arefin Md. Rajib , Kuga Kazuki , Tanimoto Jun
Published: December 2023

The COVID-19 pandemic has remarkably heightened concerns regarding the prediction of communicable disease spread. This study introduces an innovative agent-based modeling approach. In this model, the quantification of human-to-human transmission aligns with the dynamic variations in the viral load within an individual, termed “within-host” and adheres to the susceptible–infected–recovered (SIR) process, referred to as “between-host.” Variations in the viral load over time affect the infectivity between individual agents. This model diverges from the traditional SIR model, which employs a constant transmission probability, by incorporating a dynamic, time-dependent transmission probability influenced by the viral load in a host agent. The proposed model retains the time-integrated transmission probability characteristic of the conventional SIR model. As observed in this model, the overall epidemic size remains consistent with the predictions of the standard SIR model. Nonetheless, compared to predictions based on the classical SIR process, notable differences existed in the peak number of the infected individuals and the timing of this peak. These nontrivial differences are induced by the direct correlation between the time-evolving transmission probability and the viral load within a host agent. The developed model can inform targeted intervention strategies and public health policies by providing detailed insights into disease spread dynamics, crucial for effectively managing epidemics.
Establishment of oral microbiome in very low birth weight infants during the first weeks of life and the impact of oral diet implementation
Authors: Vanzele Pedro A. R. , Sparvoli Luiz Gustavo , de Camargo Patricia P. , Tragante Carla R. , Beozzo Glenda P. N. S. , Krebs Vera L. J. , Cortez Ramon V. , Taddei Carla R.
Published: December 2023

Very low birth weight (VLBW) infants, mostly preterm, have many barriers to feeding directly from the mother’s breast, and need to be fed alternatively. Feeding is a major influencer in oral microbial colonization, and this colonization in early life is crucial for the promotion of human health. Therefore, this research aimed to observe the establishment of oral microbiome in VLBW infants during their first month of life through hospitalization, and to verify the impact caused by the implementation of oral diet on the colonization of these newborns. We included 23 newborns followed during hospitalization and analyzed saliva samples collected weekly, using 16S rRNA gene sequencing. We observed a significant decrease in richness and diversity and an increase in dominance over time (q-value < 0.05). The oral microbiome is highly dynamic during the first weeks of life, and beta diversity suggests a microbial succession in early life. The introduction of oral diet does not change the community structure, but affects the abundance, especially of Streptococcus. Our results indicate that although time is related to significant changes in the oral microbial profile, oral feeding benefits genera that will remain colonizers throughout the host’s life.
Physiological changes of microalga Dunaliella parva under the treatment of PEG, CaCl2
Authors: Zou Qiman , Huang Limei , Gu Jinghui , Pang Bingbing , Shang Changhua
Published: December 2023

Carotenoids are antioxidants, which reduce various chronic diseases of human, and have many industrial applications. The halophilic Dunaliella parva (D. parva) is rich in carotenoids. The compounds CaCl2 and PEG are the popular metabolic enhancers. To further enhance carotenogenesis, D. parva was treated with two compounds polyethylene glycol (PEG) and CaCl2. Application of CaCl2 and PEG enhanced the carotenoids contents and the antioxidant activities of carotenoids compared to control group (no treatment of CaCl2 or PEG). The highest carotenoids contents were obtained by treating D. parva with 40 ppm CaCl2 (3.11 mg/g dry weight, DW) and 80 ppm PEG (2.78 mg/g DW) compared with control group (1.96 mg/g DW). When D. parva was treated with 40 ppm CaCl2 and 80 ppm PEG, protein contents reached the highest values (90.28 mg/g DW and 89.57 mg/g DW) compared to that of control group (73.42 mg/g DW). The antioxidant activities of carotenoids samples were determined. Generally, the antioxidant activities of carotenoids from D. parva treated with PEG and CaCl2 were superior to that of control group. The antioxidant activities of carotenoids mainly contained reducing power, hydroxyl radical scavenging activity and superoxide radical scavenging activity. The reducing powers of carotenoids extracts from 20 ppm CaCl2 group (2.07%/mg carotenoids) and 120 ppm PEG group (1.59%/mg carotenoids) were significantly higher than that of control group (<1.25%/mg carotenoids). The superoxide radical scavenging activities of carotenoids extracts from 40 ppm CaCl2 group (70.33%/mg carotenoids) and 80 ppm PEG group (65.94%/mg carotenoids) were significantly higher than that of control group (<55%/mg carotenoids). This paper laid a foundation for massive accumulation of carotenoids in microalga D. parva.
In silico analysis of TRPM4 variants of unknown clinical significance
Authors: Tarnovskaya Svetlana I. , Kostareva Anna A. , Zhorov Boris S.
Published: December 2023

Background

TRPM4 is a calcium-activated channel that selectively permeates monovalent cations. Genetic variants of the channel in cardiomyocytes are associated with various heart disorders, such as progressive familial heart block and Brugada syndrome. About97% of all known TRPM4 missense variants are classified as variants of unknown clinical significance (VUSs). The very large number of VUSs is a serious problem in diagnostics and treatment of inherited heart diseases.

Methods and results

We collected 233 benign or pathogenic missense variants in the superfamily of TRP channels from databases ClinVar, Humsavar and Ensembl Variation to compare performance of 22 algorithms that predict damaging variants. We found that ClinPred is the best-performing tool for TRP channels. We also used the paralogue annotation method to identify disease variants across the TRP family. In the set of 565 VUSs of hTRPM4, ClinPred predicted pathogenicity of 299 variants. Among these, 12 variants are also categorized as LP/P variants in at least one paralogue of hTRPM4. We further used the cryo-EM structure of hTRPM4 to find scores of contact pairs between parental (wild type) residues of VUSs for which ClinPred predicts a high probability of pathogenicity of variants for both contact partners. We propose that 68 respective missense VUSs are also likely pathogenic variants.

Conclusions

ClinPred outperformed other in-silico tools in predicting damaging variants of TRP channels. ClinPred, the paralogue annotation method, and analysis of residue contacts the hTRPM4 cryo-EM structure collectively suggest pathogenicity of 80 TRPM4 VUSs.
Chimeric antigen receptors enable superior control of HIV replication by rapidly killing infected cells
Authors: Zhou Yuqi , Jadlowsky Julie , Baiduc Caitlin , Klattenhoff Alex W. , Chen Zhilin , Bennett Alan D. , Pumphrey Nicholas J. , Jakobsen Bent K. , Riley James L.
Published: December 2023

Engineered T cells hold great promise to become part of an effective HIV cure strategy, but it is currently unclear how best to redirect T cells to target HIV. To gain insight, we generated engineered T cells using lentiviral vectors encoding one of three distinct HIV-specific T cell receptors (TCRs) or a previously optimized HIV-targeting chimeric antigen receptor (CAR) and compared their functional capabilities. All engineered T cells had robust, antigen-specific polyfunctional cytokine profiles when mixed with artificial antigen-presenting cells. However, only the CAR T cells could potently control HIV replication. TCR affinity enhancement did not augment HIV control but did allow TCR T cells to recognize common HIV escape variants. Interestingly, either altering Nef activity or adding additional target epitopes into the HIV genome bolstered TCR T cell anti-HIV activity, but CAR T cells remained superior in their ability to control HIV replication. To better understand why CAR T cells control HIV replication better than TCR T cells, we performed a time course to determine when HIV-specific T cells were first able to activate Caspase 3 in HIV-infected targets. We demonstrated that CAR T cells recognized and killed HIV-infected targets more rapidly than TCR T cells, which correlates with their ability to control HIV replication. These studies suggest that the speed of target recognition and killing is a key determinant of whether engineered T cell therapies will be effective against infectious diseases.
Influências da crise econômica e financeira sobre a jurisprudência do Tribunal de Justiça da União Europeia em matéria de direitos sociais
Authors: Zezza Michele
Published: December 2023

O objetivo principal do artigo consiste em refletir sobre o significado e a função dos direitos sociais no sistema da União Europeia, no cenário atual dominado pela crise econômica e financeira global, prestando especial atenção à sua relação com os limites impostos pelas restrições orçamentárias. Usando algumas ferramentas metodológicas da teoria do direito, propomos analisar certos aspectos constitutivos do raciocínio jurídico desenvolvido pelo Tribunal de Justiça da União Europeia em relação aos direitos sociais.
Omics and AI in precision medicine: Maintaining socio-technical imaginaries by transforming technological assemblages
Authors: Meunier Robert , Herzog Christian
Published: December 2023

We understand precision medicine as a socio-technical imaginary according to Jasanoff. After briefly outlining how the imaginary of precision medicine emerged from the Human Genome Project and spread across national contexts, we raise the question of why the imaginary and the expectations and promises associated with it persist despite regular disappointment among practitioners about the failure of personalized healthcare. We argue that short-term technological hypes enable stakeholders to renew and maintain the promises of precision medicine. In our view, these hypes are around transformations of a technological assemblage. We discuss this in detail for omics and AI technologies and evaluate the recent transformations in light of the long-term imaginary of precision medicine.
Labor of Minors in Industrial of Ukrainian Lands (19th – Early 20th Century)
Authors: Shandra Iryna , Birova Olha
Published: December 2023

At the present stage, the phrase “labor of minors” sounds alarming and is a sign of the low economic and cultural development of society. For the period of industrialization of the 19th – early 20th century this phenomenon was by no means a rarity, but rather one of the components of economic modernization. The Ukrainian lands were no exception in this regard, child and adolescent labor was used in coal, metallurgical, chemical and other industries.

This study is based on workers’ memories of their teenage years, memories of mining engineers, factory inspectors, public figures, as well as, albeit very scattered, statistics on the employment of minors in industry in the second half of the 19th – early 20th century. The most significant and, in this regard, reflected in the memoirs of participants in the production process, were such aspects of the work of minors as working conditions, wages, “professions” of minors, their employment statistics, the evolution of labor legislation and numerous violations of approved norms. The complex conclusion is that it took a long mutual development of public opinion, legislation and family foundations to eradicate the work of minors in industry.
Some Remarks About the Workers’ Motherhood in the Industrial City of Łódź in the 19th–20th Centuries
Authors: Śmiechowski Kamil
Published: December 2023

Łódź, the so-called “Polish Manchester”, was the biggest textile center in the Eastern Europe, which developed in the 19th century and experienced all dramatic changes that happened in Poland during the long 20th century. As the vanguard of modernity, this industrial city was the place when all the pros and cons of the early capitalism appeared in much more dramatic way then elsewhere in Poland. In a result the problem such as workers motherhood and child labor became the real social phenomenon that forced many journalists, medical doctors, factory inspector and political activists to work against them. In this article, the way in which the workers motherhood and child labor was problematized in the discourse of Łódź is analyzed as the struggle with modernity. In author’s opinion, the experience of living in the industrial cities cause that approach to such complicated social problems developed in places like Łódź is less ideological and more empathizing then nationwide one. The specific case of Łódź can be useful in refreshing the Polish debate about modernity.
The One that Wasn’t: Child and Youth Labour in the Post-Stalin Era in the Soviet Union
Authors: Studenna-Skrukwa Marta
Published: December 2023

This paper examines the phenomenon of child and youth labour in the post-Stalin era in the Soviet Union. The starting point for the consideration constitutes the analysis of the law adopted by the Supreme Soviet of the USSR in 1958 titled “On the strengthening of the link between school and life and the further development of people’s education in the USSR”. This law placed great emphasis on combining education with practice and involving pupils from the earliest grades in various forms of both productive and socially useful labour. Subsequently, four categories of labour to which children and young people in the USSR were systemically forced has been distinguished. These included: occasional labours, work and leisure camps, so-called subbotniki and little communal works, as well as compulsory recycling. The paper thoroughly depicts all of them in the light of memoir material.
Involvement of mTOR signaling in physiopathology and its potential therapeutic interventions
Authors: Martín-Bocanegra Irene , Horne Thaissa , Maqueda-Hernández Belén , Navarro-Villarán Elena , Muntané Jordi
Published: December 2023

The mammalian target of rapamycin (mTOR) is a master regulator of the cell metabolism which impacts numerous signaling involved in cell proliferation and death and recycling cell constituents to readapt to new physiological or pathological environments. mTOR is constituted by two structural and functional different complexes, mTORC1 and mTORC2. Both can be independently regulated, which has a great impact on the effectiveness of therapeutic interventions in different clinical and experimental situations. Furthermore, mTORC1 interacts with specific chaperones or immunophilins which are intracellular receptors of the immunosuppressive drugs. Low and high molecular weights of immunophilins have different intracellular functions. The present review updates the molecular structure and signaling of mTOR as well as their regulation by immunophilins and upstream and downstream signaling events, highlighting the potential therapeutic intervention of mTOR in cancer, metabolic disturbances, and aging.