bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and characterization of coconut coir biochar as potential adsorbent for removal of pharmaceutical and personal care products in wastewater
Authors: Sulistia S , Arifudin  , Sofyan M I , Abidin Z , Suherman  , Setiyono  , Sidik M A , Tanoue R , Kunisue T , Sudaryanto A
Published: September 2024

Biochar, a solid by-product of pyrolysis has attracted the attention of researchers because of it properties which is suitable for use as an adsorbent as well as energy source. As an adsorbent, biochar has similar properties to activated carbon which has high surface area, large pore volume, environmental stability, generous functional group, and high resource recovery. On the other hand, pharmaceuticals, and personal care products (PPCPs) – a class of growing environmental contaminants, are increasing public concerns for their possible effects on the ecosystem and human health. Some PPCPs are pervasive, persistent, and bioaccumulative which thus makes them easily found and currently increase in the environment, including groundwater and surface water. The main source of surface water contamination with PPCPs is due to municipal wastewater discharge that has not been adequately treated. Furthermore, due to coconut coir having a significant amount of lignin, it may be thermochemically converted into biochar with a high yield, meeting the requirements for biochar and its use in the adsorption process. This study aims to synthesize biochar from coconut coir, characterize it and determine its potential as an adsorbent for PPCPs. The biochar used for this study were characterized based on their chemical, structural and textural characteristics. The study that demonstrated good results on the adsorption of paracetamol from the aqueous phase of biochar has the potential to eliminate this pollutant by around 92%.
Estimating CO2 emission from fly ash and bottom ash collection and transport from thermal waste processing in Jakarta
Authors: Adhi R P , Setiaji R , Sunarya A F S , Pratama R A , Dewa R P , Sabudin
Published: September 2024

Municipal solid waste poses a significant challenge in DKI Jakarta Province. This study assumes that DKI Jakarta has distributed waste treatment facilities (ITFs) covering western, eastern, and southern service areas, employing thermal waste systems due to their efficiency in handling large waste volumes. However, its residual waste, Fly Ash and Bottom Ash (FABA), presents its own concerns. FABA accounts for 1.5% and 18.5% of the total waste volume in all ITFs, equivalent to 88.47 tons of fly ash and 1,091.07 tons of bottom ash daily. The study analyses total distance travelled and fuel consumption for FABA transportation from each ITF to designated disposal sites. The planned fleet is 12-ton capacity truck or equivalent. Arc-GIS is employed for trip assignment and generate daily trip requirements. Three FABA disposal scenarios are considered: TPST Bantargebang, certified third-party sites in Gunung Putri, and a combination of both. The daily total distance ranges from 8,247.96 to 10,026.48 km and consume 5,071.16 to 6,164.66 Liters of biosolar. The trip assignment reveals that the distance to Gunung Putri exceeds the other alternatives, while transporting FABA to TPST Bantargebang yields the lowest total distance travelled. Estimated CO2 emissions range from 11.22 to 13.64 tons per day.
Building a resilient North Jakarta: Integrating social preferences for effective adaptation and mitigation strategy in the climate change era
Authors: Adibroto T A , Wijayanti P , Pratama R A , Adhi R P , Ihsan I M , Handika R , Musirin S D R H
Published: September 2024

The northern part of Jakarta, Indonesia, has been grappling with recurring floods due to climate change, affecting residents’ lives and livelihoods. Sea level rise, land subsidence, and increased precipitation increase the risk of river flooding. While the government has implemented physical flood mitigation measures, these alone are insufficient due to climate uncertainty. This 2017 study assesses socio-cultural risks in northern Jakarta and community preferences for climate change adaptation strategies. The study was conducted in 2017 and the study’s insights remain relevant to contributed as one of the scientific basis for the statutory planning of Jakarta to build the social resilience. Employing qualitative approaches, it collected data at mezzo and micro levels. Findings show that households adopt various private and public mitigation-adaptation measures. Most prefer elevating household items to higher ground (62.9%), while 44% favor maintaining the local drainage system and improving pumping facilities. However, 62% resist relocating to vertical houses, fearing job loss or increased expenses. Only 13% express willingness to relocate voluntarily for more comfortable housing. This resistance stems from the apprehension that such relocation might negatively impact their overall welfare, either by jeopardizing their employment opportunities or by increasing their monthly expenditures.
Closed-loop adaptive optics in the presence of speckle and weak scintillation
Authors: Burrell Derek J , Spencer Mark F , Driggers Ronald G
Published: September 2024

In this paper, we show that speckle averaging helps to improve adaptive-optics (AO) performance in closed loop as a result of reduced measurement error associated with a Shack–Hartmann wavefront sensor (SHWFS); however, this reduction is rendered ineffective with increasing beacon anisoplanatism. We do so operating in a weak-scintillation regime, where the SHWFS offers robust performance, and using in-plane translation of the illuminated rough surface to accomplish frame-to-frame speckle diversity. Understanding these trade-space limitations is critical when performing AO with non-cooperative, extended-source beacons.
Some parametric 𝑞-supercongruences from a summation of Gasper and Rahman
Authors: He Haihong , Wang Xiaoxia
Published: September 2024

By employing a quadratic summation formula due to Gasper and Rahman [Basic hypergeometric series, 2nd ed, vol. 96, Cambridge University Press, Cambridge, 2004] and the creative microscoping method developed by Guo and Zudilin [Adv. Math. 346 (2019), pp. 329–358], we establish some new parametric

q
q

-supercongruences, the corresponding supercongruences of which can be deemed the variants of Van Hamme’s (J.2) and (L.2) supercongruences. Moreover, we obtain three families of Ramanujan-type formulas on

π
\pi

and propose a challenging conjecture.
Increasing Temporal Sensitivity of Omics Association Studies with Epigenome-Wide Distributed Lag Models
Authors: Parikh Milan N , Manning Erika Rasnick , Niu Liang , Ruehlmann Anna Kotsakis , Folger Alonzo T , Brunst Kelly J , Brokamp Cole
Published: September 2024

Current methods for identifying temporal windows of effect for time-varying exposures in omics settings can control false discovery rates at the biomarker-level but cannot efficiently screen for timing-specific effects in high dimensions. Current approaches leverage separate models for site screening and identification of susceptible time windows, which miss associations that vary over time. We introduce the epigenome-wide distributed lag model (EWDLM), a novel approach that combines traditional false discovery rate methods with the distributed lag model (DLM) to screen for timing-specific effects in high dimensional settings. This is accomplished by marginalizing DLM effect estimates over time and correcting for multiple comparisons. In a simulation investigating timing-specific effects of ambient air pollution during pregnancy on DNA methylation across the epigenome at age 12 years, EWDLM achieved an increased sensitivity for associations limited to specific periods of time compared to traditional two-stage approaches. In a real-world EWDLM analysis, 353 CpG sites at which DNAm measured at age 12 was significantly associated with PM2.5 exposure during pregnancy were identified. EWDLM is a novel method that provides an efficient and sensitive way to screen epigenomic datasets for associations with exposures localized to specific time periods.
Hard Choices and Ultimate Ends
Authors: Costella Annalisa
Published: September 2024

I propose a novel view on hard choices. It broadens the concept to include not only ‘classic’ hard choices but also transformative and aspirational choices. I argue that a choice is hard when an individual does not have an all-things-considered reason to choose one option over another and the objects of choice are ultimate ends. Construing hard choices in this way supports and explains the widely held assumption that, when faced with hard choices, it is impermissible to choose arbitrarily. More specifically, it shows that it is impermissible to choose arbitrarily by plumping, and yet legitimate to do so by picking. Understanding hard choices in the way I propose sheds light on the fact that there are moral and agential constraints that limit the space of permissible decision-making procedures when confronted with ‘classic’ hard, transformative, and aspirational choices. Delineating these constraints, in turn, can provide guidance to critically appraise current theories of practical rationality.
Baseline MRI predictors of successful organ preservation in the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial
Authors: Williams Hannah , Yuval Jonathan B , Verheij Floris S , Miranda Joao , Lin Sabrina T , Omer Dana M , Qin Li-Xuan , Gollub Marc J , Kim Tae-Hyung , Garcia-Aguilar Julio ,   OPRA Consortium, Patil S , Kim J K , Thompson H M , Marco M R , Lee M , Paty P B , Weiser M R , Nash G M , Pappou E , Wei I H , Widmar M , Segal N H , Cercek A , Yaeger R , Smith J J , Wu A J , Saltz L B , Dunne R F , Temple L , Marcet J , Cataldo P , Polite B , Herzig D O , Liska D , Oommen S , Friel C M , Ternent C , Coveler A L , Hunt S , Gregory A , Varma M G , Bello B L , Carmichael J C , Krauss J , Gleisner A , Guillem J G , Goodman K A
Published: September 2024

Background

Prospective randomized trials have not yet identified baseline features predictive of organ preservation in locally advanced rectal cancers treated with total neoadjuvant therapy and a selective watch-and-wait strategy.

Methods

This was a secondary analysis of the OPRA trial, which randomized patients with stage II–III rectal adenocarcinoma to receive either induction or consolidation total neoadjuvant therapy. Patients were recommended for total mesorectal excision, or watch and wait based on clinical response at 8 ± 4 weeks after completing treatment. Standardized baseline clinical and radiological variables were collected prospectively. Survival outcomes, including total mesorectal excision-free survival, disease-free survival, and overall survival, were assessed by intention-to-treat analysis. Cox proportional hazards models were used to evaluate associations between baseline variables and survival outcomes.

Results

Of the 324 patients randomized for the OPRA trial, 38 (11.7%) had cT4 tumours, 230 (71.0%) cN-positive disease, 101 (32.5%) mesorectal fascia involvement, and 64 (19.8%) extramural venous invasion. Several baseline features were independently associated with recommendation for total mesorectal excision on multivariable analysis: nodal disease (HR 1.66, 95% c.i. 1.12 to 2.48), extramural venous invasion (HR 1.57, 1.07 to 2.29), mesorectal fascia involvement (HR 1.45, 1.01 to 2.09), and tumour length (HR 1.11, 1.00 to 1.22). Of these, nodal disease (HR 2.02, 1.15 to 3.53) and mesorectal fascia involvement (HR 2.02, 1.26 to 3.26) also predicted worse disease-free survival. Age (HR 1.03, 1.00 to 1.06) was associated with overall survival.

Conclusion

Baseline MRI features, including nodal disease, extramural venous invasion, mesorectal fascia involvement, and tumour length, independently predict the likelihood of organ preservation after completion of total neoadjuvant therapy. Mesorectal fascia involvement and nodal disease are associated with disease-free survival.
BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis
Authors: Bergner Caroline Gertrud , van der Meer Franziska , Franz Jonas , Vakrakou Aigli , Würfel Thea , Nessler Stefan , Schäfer Lisa , Nau-Gietz Cora , Winkler Anne , Lagumersindez-Denis Nielsen , Wrzos Claudia , Damkou Ioanna Alkmini , Sergiou Christina , Schultz Verena , Knauer Carolin , Metz Imke , Bahn Erik , Rodriguez Enrique Garea , Merkler Doron , Simons Mikael , Stadelmann Christine
Published: September 2024

Remyelination is a crucial regenerative process in demyelinating diseases, limiting persisting damage to the CNS. It restores saltatory nerve conduction and ensures trophic support of axons. In patients with multiple sclerosis, remyelination has been observed in both white and grey matter and found to be more efficient in the cortex. Brain-enriched myelin-associated protein 1 (BCAS1) identifies oligodendrocyte lineage cells in the stage of active myelin formation in development and regeneration. Other than in the white matter, BCAS1+ oligodendrocytes are maintained at high densities in the cortex throughout life.

Here, we investigated cortical lesions in human biopsy and autopsy tissue from patients with multiple sclerosis in direct comparison to demyelinating mouse models and demonstrate that following a demyelinating insult BCAS1+ oligodendrocytes in remyelinating cortical lesions shift from a quiescent to an activated, internode-forming morphology co-expressing myelin-associated glycoprotein (MAG), necessary for axonal contact formation. Of note, activated BCAS1+ oligodendrocytes are found at early time points of experimental demyelination amidst ongoing inflammation. In human tissue, activated BCAS1+ oligodendrocytes correlate with the density of myeloid cells, further supporting their involvement in an immediate regenerative response.

Furthermore, studying the microscopically normal appearing non demyelinated cortex in patients with chronic multiple sclerosis, we find a shift from quiescent BCAS1+ oligodendrocytes to mature, myelin-maintaining oligodendrocytes, suggesting oligodendrocyte differentiation and limited replenishment of BCAS1+ oligodendrocytes in long-standing disease. We also demonstrate that part of perineuronal satellite oligodendrocytes are BCAS1+ and contribute to remyelination in human and experimental cortical demyelination.

In summary, our results provide evidence from human tissue and experimental models that BCAS1+ cells in the adult cortex represent a population of pre-differentiated oligodendrocytes that rapidly react after a demyelinating insult thus enabling immediate myelin regeneration. In addition, our data suggest that limited replenishment of BCAS1+ oligodendrocytes may contribute to the remyelination failure observed in the cortex in chronic multiple sclerosis.
Lessons on neurodegeneration and aging from the Lagoon of Venice: the marine invertebrate Botryllus schlosseri
Authors: Bocci Tommaso , Anselmi Chiara , La Torre Federico , De Lisa Emanuela , Sabbadin Giacomo , Guidetti Matteo , Maiorana Natale , Priori Alberto , Manni Lucia
Published: September 2024

In this work, the authors proposed a novel and interesting animal model for studying human neurodegenerative diseases, Botryllus schlosseri, a small invertebrate inhabiting temperate seas worldwide, which shares remarkable similarities with mammals in the expression of genes involved in pathological aging.
Phenotypic characterization of people at risk of atrial fibrillation: protocol for the FIND-AF longitudinal cohort study
Authors: Wahab Ali , Nadarajah Ramesh , Reynolds Catherine , Bennett Sheena , Ambakederemo Edisemi , Harris Mohammad , Younsi Tanina , Joseph Tobin , Raveendra Keerthenan , Smith Adam , Bhatty Asad , Lip Gregory Y H , Swoboda Peter P , Wu Jianhua , Gale Chris P
Published: September 2024

Aims

The Future Innovations in Novel Detection of Atrial Fibrillation (FIND-AF) longitudinal cohort study is a multi-centre prospective cohort study of patients identified at risk of atrial fibrillation (AF). The aim of the FIND-AF longitudinal cohort study is to provide multi-modal phenotypic characterization of these patients.

Methods and results

A total of 1955 participants identified as at risk of AF by the FIND-AF algorithm from primary care electronic health record (EHR) data, aged 30 years and above and eligible for oral anticoagulation, will be recruited between October 2023 and November 2024 to receive home-based intermittent electrocardiogram monitoring. About 500 participants without diagnosed AF will then undergo cross-sectional phenotypic characterization including physical examination, symptoms assessment, serum blood biomarkers and echocardiography, and non-stress cardiac magnetic resonance imaging. Longitudinal information about cardio–renal–metabolic–pulmonary outcomes will be ascertained from linkages to EHR data. The study is funded by the British Heart Foundation (CC/22/250026). The study has ethical approval (North West—Greater Manchester South Research Ethics Committee reference 23/NW/0180). Findings will be announced at relevant conferences and published in peer-reviewed journals in line with the funder’s open-access policy.

Conclusion

The FIND-AF multi-centre prospective longitudinal cohort study aims to (i) provide evidence for the impact of comorbidities on AF genesis, (ii) uncover actionable targets to prevent AF, and (iii) act as a platform for cohort randomized clinical trials that investigate enhanced detection and prevention of AF.
The role of family and environment in determining the skin bacterial communities of captive aquatic frogs, Xenopus laevis
Authors: Chapman Phoebe A , Hudson Daniel , Morgan Xochitl C , Beck Caroline W
Published: September 2024

Skin microbes play an important role in amphibian tissue regeneration. Xenopus spp. (African clawed frogs) are well-established model organisms, and standard husbandry protocols, including use of antibiotics, may affect experimental outcomes by altering bacterial assemblages. It is therefore essential to improve knowledge of Xenopus bacterial community characteristics and inheritance. We undertook bacterial 16S rRNA gene sequencing and source tracking of a captive Xenopus laevis colony, including various life stages and environmental samples across multiple aquarium systems. Tank environments supported the most complex bacterial communities, while egg jelly bacteria were the most diverse of frog life stages; tadpole bacterial communities were relatively simple. Rhizobium (Proteobacteria) and Chryseobacterium (Bacteroidota) were dominant in tadpoles, whereas Chryseobacterium, Vogesella (Proteobacteria), and Acinetobacter (Proteobacteria) were common in females. Tadpoles received approximately two-thirds of their bacteria via vertical transmission, though 23 genera were differentially abundant between females and tadpoles. Female frog skin appears to select for specific taxa, and while tadpoles inherit a proportion of their skin bacteria from females via the egg, they support a distinct and less diverse community. The outcomes of this study suggest the impacts of breaking the bacterial transmission chain with antibiotic treatment should be considered when raising tadpoles for experimental purposes.
Deep mutational scanning of CYP2C19 in human cells reveals a substrate specificity-abundance tradeoff
Authors: Boyle Gabriel E , Sitko Katherine A , Galloway Jared G , Haddox Hugh K , Bianchi Aisha Haley , Dixon Ajeya , Wheelock Melinda K , Vandi Allyssa J , Wang Ziyu R , Thomson Raine E S , Garge Riddhiman K , Rettie Allan E , Rubin Alan F , Geck Renee C , Gillam Elizabeth M J , DeWitt William S , Matsen Frederick A , Fowler Douglas M
Published: September 2024

The cytochrome P450s enzyme family metabolizes ∼80% of small molecule drugs. Variants in cytochrome P450s can substantially alter drug metabolism, leading to improper dosing and severe adverse drug reactions. Due to low sequence conservation, predicting variant effects across cytochrome P450s is challenging. Even closely related cytochrome P450s like CYP2C9 and CYP2C19, which share 92% amino acid sequence identity, display distinct phenotypic properties. Using variant abundance by massively parallel sequencing, we measured the steady-state protein abundance of 7,660 single amino acid variants in CYP2C19 expressed in cultured human cells. Our findings confirmed critical positions and structural features essential for cytochrome P450 function, and revealed how variants at conserved positions influence abundance. We jointly analyzed 4,670 variants whose abundance was measured in both CYP2C19 and CYP2C9, finding that the homologs have different variant abundances in substrate recognition sites within the hydrophobic core. We also measured the abundance of all single and some multiple wild type amino acid exchanges between CYP2C19 and CYP2C9. While most exchanges had no effect, substitutions in substrate recognition site 4 reduced abundance in CYP2C19. Double and triple mutants showed distinct interactions, highlighting a region that points to differing thermodynamic properties between the 2 homologs. These positions are known contributors to substrate specificity, suggesting an evolutionary tradeoff between stability and enzymatic function. Finally, we analyzed 368 previously unannotated human variants, finding that 43% had decreased abundance. By comparing variant effects between these homologs, we uncovered regions underlying their functional differences, advancing our understanding of this versatile family of enzymes.
PhageGE: an interactive web platform for exploratory analysis and visualization of bacteriophage genomes
Authors: Zhao Jinxin , Han Jiru , Lin Yu-Wei , Zhu Yan , Aichem Michael , Garkov Dimitar , Bergen Phillip J , Nang Sue C , Ye Jian-Zhong , Zhou Tieli , Velkov Tony , Song Jiangning , Schreiber Falk , Li Jian
Published: September 2024

Background

Antimicrobial resistance is a serious threat to global health. Due to the stagnant antibiotic discovery pipeline, bacteriophages (phages) have been proposed as an alternative therapy for the treatment of infections caused by multidrug-resistant pathogens. Genomic features play an important role in phage pharmacology. However, our knowledge of phage genomics is sparse, and the use of existing bioinformatic pipelines and tools requires considerable bioinformatic expertise. These challenges have substantially limited the clinical translation of phage therapy.

Findings

We have developed PhageGE (Phage Genome Explorer), a user-friendly graphical interface application for the interactive analysis of phage genomes. PhageGE enables users to perform key analyses, including phylogenetic analysis, visualization of phylogenetic trees, prediction of phage life cycle, and comparative analysis of phage genome annotations. The new R Shiny web server, PhageGE, integrates existing R packages and combines them with several newly developed functions to facilitate these analyses. Additionally, the web server provides interactive visualization capabilities and allows users to directly export publication-quality images.

Conclusions

PhageGE is a valuable tool that simplifies the analysis of phage genome data and may expedite the development and clinical translation of phage therapy. PhageGE is publicly available at https://jason-zhao.shinyapps.io/PhageGE_Update/.
Intestinal Epithelial Tight Junction Barrier Regulation by Novel Pathways
Authors: Arumugam Priya , Saha Kushal , Nighot Prashant
Published: September 2024

Intestinal epithelial tight junctions (TJs), a dynamically regulated barrier structure composed of occludin and claudin family of proteins, mediate the interaction between the host and the external environment by allowing selective paracellular permeability between the luminal and serosal compartments of the intestine. TJs are highly dynamic structures and can undergo constant architectural remodeling in response to various external stimuli. This is mediated by an array of intracellular signaling pathways that alters TJ protein expression and localization. Dysfunctional regulation of TJ components compromising the barrier homeostasis is an important pathogenic factor for pathological conditions including inflammatory bowel disease (IBD). Previous studies have elucidated the significance of TJ barrier integrity and key regulatory mechanisms through various in vitro and in vivo models. In recent years, considerable efforts have been made to understand the crosstalk between various signaling pathways that regulate formation and disassembly of TJs. This review provides a comprehensive view on the novel mechanisms that regulate the TJ barrier and permeability. We discuss the latest evidence on how ion transport, cytoskeleton and extracellular matrix proteins, signaling pathways, and cell survival mechanism of autophagy regulate intestinal TJ barrier function. We also provide a perspective on the context-specific outcomes of the TJ barrier modulation. The knowledge on the diverse TJ barrier regulatory mechanisms will provide further insights on the relevance of the TJ barrier defects and potential target molecules/pathways for IBD.
An unconditionally energy dissipative, adaptive IMEX BDF2 scheme and its error estimates for Cahn–Hilliard equation on generalized SAV approach
Authors: Wei Yifan , Zhang Jiwei , Zhao Chengchao , Zhao Yanmin
Published: September 2024

An adaptive implicit-explicit (IMEX) BDF2 scheme is investigated on generalized SAV approach for the Cahn–Hilliard equation by combining with Fourier spectral method in space. It is proved that the modified energy dissipation law is unconditionally preserved at discrete levels. Under a mild ratio restriction, i.e., A1: $0<r_{k}:=\tau _{k}/\tau _{k-1}< r_{\max }\approx 4.8645$, we establish a rigorous error estimate in $H^{1}$-norm and achieve optimal second-order accuracy in time. The proof involves the tools of discrete orthogonal convolution (DOC) kernels and inequality zoom. It is worth noting that the presented adaptive time-step scheme only requires solving one linear system with constant coefficients at each time step. In our analysis, the first-consistent BDF1 for the first step does not bring the order reduction in $H^{1}$-norm. The $H^{1}$ bound of numerical solution under periodic boundary conditions can be derived without any restriction (such as zero mean of the initial data). Finally, numerical examples are provided to verify our theoretical analysis and the algorithm efficiency.
Senescence-associated T cells in immunosenescence and diseases
Authors: Fukushima Yuji , Ueno Ryuji , Minato Nagahiro , Hattori Masakazu
Published: September 2024

Age-related changes in the immune system, referred to as immunosenescence, appear to evolve with rather paradoxical manifestations, a diminished adaptive immune capacity, and an increased propensity for chronic inflammation often with autoimmunity, which may underlie the development of diverse disorders with age. Immunosenescent phenotypes are associated with the emergence of unique lymphocyte subpopulations of both T and B lineages. We report that a CD153+ programmed cell death protein 1 (PD-1)+ CD4+ T-cell subpopulation with severely attenuated T-cell receptor (TCR)-responsiveness, termed senescence-associated T (SAT) cells, co-evolve with potentially autoreactive CD30+ B cells, such as spontaneous germinal center B cells and age-associated B cells, in aging mice. SAT cells and CD30+ B cells are reciprocally activated with the aid of the interaction of CD153 with CD30 in trans and with the TCR complex in cis, resulting in the restoration of TCR-mediated proliferation and secretion of abundant pro-inflammatory cytokines in SAT cells and the activation and production of autoantibodies by CD30+ B cells. Besides normal aging, the development of SAT cells coupled with counterpart B cells may be robustly accelerated and accumulated in the relevant tissues of lymphoid or extra-lymphoid organs under chronic inflammatory conditions, including autoimmunity, and may contribute to the pathogenesis and aggravation of the disorders. This review summarizes and discusses recent advances in the understanding of SAT cells in the contexts of immunosenescent phenotypes, as well as autoimmune and chronic inflammatory diseases, and it provides a novel therapeutic clue.
The Beast Computer of Brussels: An American Invention That Conquered the World
Authors: Clay J Eugene
Published: September 2024

In 1972, the American Pentecostal preacher David Wilkerson produced a fifty-minute film, The Rapture, depicting “the return of Jesus Christ.” Subtly alluding to the apocalyptic “mark of the beast” (Revelation 13:16–18), the film featured a gigantic computer called “the Beast.” Located in Brussels, the Beast controlled global commerce by tracking every human on earth with numbers “invisibly ‘laser’ tatooed on the forehead or the back of the hand.” Within months of the film’s release, American Evangelical Protestant networks were reporting the existence of the beast computer as an actual fact and spread the story worldwide. By the 1980s, Greek and Russian Orthodox Christians, skeptical of the European Community, eagerly integrated the beast computer into their own eschatologies. The legend demonstrates the dynamism of the American evangelical imagination, which created this flexible symbol of globalization and technology, as well as the power of the global networks that disseminated it.
Therapeutic drug monitoring-guided piperacillin dosing in critically ill patients undergoing continuous renal replacement therapy: a systematic review
Authors: Mohd Rozi Nazatul Adhwa , Mohd Tahir Nor Asyikin , Mohd Saffian Shamin , Makmor-Bakry Mohd , Mohamad Yusof Aliza , Mustafar Ruslinda , M Saud Muhammad Nordin
Published: September 2024

Background

Continuous renal replacement therapy (CRRT) complicates antibiotic dosing in critically ill patients due to altered pharmacokinetics. The optimal dosing of piperacillin remains unclear. Therapeutic drug monitoring (TDM) can personalize piperacillin therapy and improve outcomes.

Objectives

This review investigates the effects of TDM-guided piperacillin dosing on pharmacokinetic target attainment and clinical outcomes in CRRT patients, analyses correlations with clinical outcomes, provides optimal dosing strategies for piperacillin and identifies future research areas.

Methods

A systematic search of PubMed, Scopus and Web of Science was conducted until December 2023, identifying studies on piperacillin pharmacokinetics and clinical outcomes in adult CRRT patients. Data on study characteristics, piperacillin exposures, TDM use, target attainment rates, mortality and length of stay were extracted. The risk of bias was assessed using the Newcastle–Ottawa Scale.

Results

Eleven observational studies were included. High pharmacokinetic variability was evident, with piperacillin target non-attainment in up to 74% of cases without TDM. Two studies with routine TDM showed increased target attainment rates of 80%–100%. Mortality ranged from 17% to 56%, with supratherapeutic concentrations (≥100 mg/L) associated with higher mortality. The impact of optimized piperacillin exposures on outcomes was inconclusive. Most studies demonstrated a low risk of bias.

Conclusions

TDM-guided piperacillin dosing in CRRT patients improved target attainment rates (≥80%). Mortality rates ranged from 17% to 56%, with inconsistent correlations between drug exposures and survival. Supratherapeutic concentrations were linked to higher mortality. Standardized TDM protocols are needed. Future research should establish clear exposure–response relationships and the impact of TDM on clinical outcomes.
Daily intake of household-produced milk kefir on Salmonella Typhimurium infection in C57BL/6 mice: mortality, microbiota modulation, and immunological implications
Authors: Albuquerque Pereira Mariana de Fátima , Morais de Ávila Larissa Gabriela , dos Santos Cruz Bruna Cristina , Almeida Lucas Filipe , Macedo Simões Jordana , Campos Silva Bruno , Pereira Aguilar Ananda , de Oliveira Leandro Licursi , Vilela Gonçalves Reggiani , Ribon Andréa de Oliveira Barros , Mendes Tiago Antônio de Oliveira , Gouveia Peluzio Maria do Carmo
Published: September 2024

Aims

Salmonellosis, a major global cause of diarrheal diseases, significantly impacts the intestinal microbiome. Probiotic-rich beverages, such as kefir, are increasingly utilized as alternative health-promoting beverages associated with various microbiota benefits. This study investigated the repercussions of daily consumption of household-produced milk kefir on Salmonella enterica serovar Typhimurium infection in C57BL-6 mice.

Methods and results

Kefir consumption pre-infection reduced the presence of inflammatory cells in the colon and altered the cytokine profile by reducing IL-10 and increasing IFN-γ. Despite reducing intestinal inflammation, kefir intake did not yield a prompt response to an acute infection caused by the aggressive pathogen Salmonella. This contributed to increased mortality in the mice, evidenced by higher fecal Salmonella counts post-infection. Metabarcoding analysis demonstrated that the use of kefir before infection increases butyric acid by the higher abundance of Lachnospiraceae and Prevotellaceae families and genus in feces, coupled with an increase in Muribaculaceae family and Bacteroides genus among infected kefir-treated mice. While kefir hinted at microbiota alterations reducing enterobacteria (Helicobacter), decrease IL-10, and increased IFN-γ, butyric acid on pre-infection, the beverage potentially facilitated the systemic translocation of pathogens, intensifying the infection’s severity by altering the immune response.

Conclusions

The use of kefir in the dosage of 10% w/v (109 CFU), for acute infections with Salmonella Typhimurium, may not be enough to combat the infection and worsen the prognosis, leaving the intestine less inflamed, favoring the replication and translocation of the pathogen. These findings underscore the importance of prudently evaluating the widespread use of probiotics and probiotic-rich beverages, especially during acute infections, given their potential association with adverse effects during these diseases.
A blend of bacillus-fermented soybean meal, functional amino acids, and nucleotides improves nutrient digestibility, bolsters immune response, reduces diarrhea, and enhances growth performance in weaned piglets
Authors: Van Tran Thang , Kim Yang Su , Yun Hyeon Ho , Nguyen Dinh Hai , Bui Thom Thi , Van Tran Phung
Published: September 2024

This study investigated the effects of a blend of bacillus-fermented soybean meal, functional amino acids, and nucleotides (Functional protein blend-FP Blend) as a replacement for animal protein sources in a weaner pig diet without antibiotic growth promoters on nutrient digestibility, blood profiles, intestinal morphology, diarrhea incidence, and growth performance. A total of 288 crossbred weaned piglets [♂ Duroc x ♀ (Yorkshire × Landrace)] with an average body weight (BW) of 6.89 ± 0.71 kg were randomly allocated to 6 groups based on initial BW and sex (8 replicate pens per treatment; 3 gilts and 3 barrows/pen). The experiment lasted for 5 wk. Dietary treatments included PC [standard diet with 3% fish meal (FM) and 2% plasma protein (PP)], NC (nonanimal protein, AP), T1 (3% FM replaced with 5% FP Blend), T2 (3% FM and 1% PP replaced with 5% FP Blend), T3 (2% PP replaced with 5% FP Blend), and T4 (3% FM and 2% PP replaced with 5% FP Blend). Data were analyzed using Minitab version 17 software. Key results indicated that FP Blend improved the apparent ileal digestibility (AID) coefficient of dry matter, gross energy, lysine, and valine in T4 compared with NC treatment (P < 0.05), whereas AID coefficient of crude protein and other amino acids remained constant (P > 0.05). Compared with NC diet, the weaned pigs fed T4 diet reduced malondialdehyde, serum IL8, TNF-α, and increased IgG (P < 0.05), while showing no effect on serum IL6, IL10, white blood cells, IgA, and endotoxin (P > 0.05). Furthermore, FP blend significantly increased villus height in the duodenum and ileum in T4 compared with NC (P < 0.05). The average daily gain (ADG) was highest in T4 (502.73 g/d), followed by T1 (477.96 g/d) and T2 (475.85 g/d), compared with PC (450.86 g/d) and NC (439.79 g/d). T4’s ADG significantly differed from PC and NC (P < 0.001), whereas no significant differences were observed in T1, T2, and T3 (P > 0.05). The feed conversion ratio (FCR) was significantly lower in T4 (1.45) compared with PC (1.57) and NC (1.59) (P < 0.001), with no significant differences among other groups. In conclusion, FP Blend demonstrated efficacy in improving nutrient digestibility, optimizing intestinal morphology, bolstering immune responses, reducing diarrhea incidence, alleviating the adverse effects of weaning stress, and enhancing growth performance of weaned piglets.
Machine heuristic: concept explication and development of a measurement scale
Authors: Yang Hyun , Sundar S Shyam
Published: September 2024

Human assumption of superior performance by machines has a long history, resulting in the concept of “machine heuristic” (MH), which is a mental shortcut that individuals apply to automated systems. This article provides a formal explication of this concept and develops a new scale based on three studies (Combined N = 1129). Measurement items were derived from the explication and an open-ended survey (Study 1, N = 270). These were then administered in a closed-ended survey (Study 2, N = 448) to identify their dimensionality through exploratory factor analysis (EFA). Lastly, we conducted another survey (Study 3, N = 411) to verify the factor structure obtained in Study 2 by employing confirmatory factor analysis (CFA). Analyses resulted in a validated scale of seven items that reflect the level of MH in individuals and identified six sets of descriptive labels for machines (expert, efficient, rigid, superfluous, fair, and complex) that serve as formative indicators of MH. Theoretical and practical implications are discussed.
Anemia in patients with cartilage hair hypoplasia: a narrative review and recommendations
Authors: Lewandowska Natalia , Ordak Michal
Published: September 2024

Cartilage hair hypoplasia (CHH) can lead to the development of anemia as a possible complication of this rare genetic disease. Despite various publications on anemia in CHH patients, a comprehensive review on this topic has not been conducted. This article reviews publications on anemia in CHH patients published from 1981 to 2022. Most authors have reported macrocytic anemia and blood transfusion as a common treatment approach in this patient group. Recommended guidelines for managing anemia in CHH patients include iron chelation therapy for those requiring multiple blood transfusions, regular assessment of anemia symptoms, red blood cell parameters, and immune system function. Future studies should evaluate the erythroid system in a larger cohort of CHH patients, considering key factors such as concurrent illnesses, age, height, and weight.
CHARGE Syndrome
Authors: Clark Robin D. , Curry Cynthia J.
Published: September 2024

This chapter reviews background information about the prevalence, recurrence risk, family history (advanced paternal age), clinical features and genetic etiology of CHARGE syndrome. The clinical presentation during infancy includes most of the anomalies that make up the acronym: coloboma of the iris or retina, heart defect, atresia choanae, retardation of growth or development, genitourinary anomalies and ear anomalies or hearing loss. Facial palsy, semicircular canal hypoplasia, and cleft lip/palate are also common features. The differential diagnosis includes teratogens (alcohol, hydantoin, isotretinoin) and chromosome anomalies (aneuploidy, cat eye syndrome and other copy number variants) and single gene disorders that include choanal atresia or colobomas. The early mortality of CHARGE syndrome is described. Recommendations for testing, evaluation, and management are provided.
Diabetic Embryopathy
Authors: Clark Robin D. , Curry Cynthia J.
Published: September 2024

This chapter reviews the incidence, etiology, and variable phenotypes seen in diabetic embryopathy. Pregestational diabetics have the highest risks for anomalies and these risks also correlate with the HgbA1C level. Increased risks for isolated birth defects include neural tube defects, holoprosencephaly, several types of congenital heart disease including heterotaxy, renal agenesis and orofacial clefts. Patterns of malformation in IDM infants include VACTERL association, Femoral-Facial syndrome, Caudal regression and oculoauriculovertebral spectrum. Several neonatal issues including hypertrophic cardiomyopathy, feeding dysfunction and small left colon syndrome are seen in these infants. Tight glycemic control in subsequent planned pregnancies will reduce risks for recurrence of birth defects.
Noonan Syndrome and Related Disorders
Authors: Clark Robin D. , Curry Cynthia J.
Published: September 2024

This chapter reviews the incidence and etiology of Noonan syndrome (NS) and related disorders in the RAS–MAPK pathway. The prenatal presentations of NS, CFC syndrome and Costello syndrome are reviewed with the emphasis on possibly distinquishing these conditions in-utero. Clinically unique and overlapping features at birth are emphasized. Other forms of NS are listed including NS with lentigines and NS with loose anagen hair. Neurofibromatosis 1 is also discussed although this disorder is rarely diagnosed in newborns. Complications seen in infancy are reviewed. Recommendations for RAS pathway gene panel testing, echocardiography, developmental follow up and imaging are enumerated.
Smith–Lemli–Opitz Syndrome
Authors: Clark Robin D. , Curry Cynthia J.
Published: September 2024

This chapter reviews the incidence, etiology, and biochemical basis of Smith–Lemli–Opitz syndrome, a metabolic disorder of cholesterol metabolism, characterized by multiple anomalies and dysmorphic features. Prenatal findings include a very low maternal serum estriol. The clinical presentation during infancy includes multiple system abnormalities such as cleft palate. post-axial polydactyly and Y shaped 2-3 toe syndactyly, poor feeding, hypotonia, and failure to thrive. Early demise can occur in severely involved infants but mildly affected patients may escape detection for months or years. Sequence analysis of DHCR7 confirms the diagnosis. Treatment protocols are available but changes in intellectual functioning with cholesterol supplementation is minimal although behavior may improve. The differential diagnosis is fairly narrow, including Fanconi syndrome, TARP syndrome and some chromosomal aneuploidies.
Williams Syndrome
Authors: Clark Robin D. , Curry Cynthia J.
Published: September 2024

This chapter reviews background information about the incidence, genetics, etiology, and chromosomal nature of Williams syndrome, which is caused by a contiguous gene deletion on chromosome 7q11.23. This is usually a sporadic disorder that is rarely familial. The clinical presentation during infancy is characterized by supravalvular stenosis of the aorta and a characteristic “elfin” face with periorbital puffiness and full lips. Common co-morbidities include irritability, colic, hypercalcemia, feeding difficulties and renal anomalies. Late manifestations are reviewed to facilitate counseling the family. The differential diagnosis and prognosis of Williams syndrome are reviewed. Recommendations for genetic testing, evaluation, management and resources are provided.
Exploring Digital Zoom in Scanning Electron Microscopy
Authors: Brake Gary
Published: September 2024

The concept of zoom in scanning electron microscopy (SEM) once referred to increasing the magnification of the sample by reducing the scanned field size. However, with the introduction of digital technology, the concept of zooming has become a little more complicated. Historically, older SEMs operated at a 512 × 512-pixel lateral resolution (262 kB pixel density) at TV scan rates. Today's newest SEMs can achieve up to 32k × 24k (4:3 ratio) pixel lateral resolution, equating to an 805 MB pixel density. In this article, we explore the factors involved in selecting an appropriate frame grabber size for SEM imaging. Specifically, we will delve into the implications of pixel density, including its impact on digital zoom capabilities, image file sizes, and overall image acquisition times.
Experiences of transgender migrants from Kyrgyzstan, Kazakhstan, Tajikistan, Armenia, and Uzbekistan living in Russia
Authors: Kirey-Sitnikova Yana
Published: September 2024

Despite Russia being a major migrant-receiving country, it does not receive adequate attention in international literature, especially in relation to migrants belonging to marginalized groups. Based on interviews with seventeen transgender (trans) migrants from Central Asia and the South Caucasus with an experience of living in Russia, the study revealed the complex intersections between transphobia, migrantophobia, racism, and whorephobia. The migrants faced profound workplace discrimination and suffered from police and ultra-right groups. Cisgender migrants caring for the prestige of their nation and trans migrant sex workers striving to annihilate competitors were described as additional threats. Russian trans/LGBT organizations were reported to be difficult to access and their priorities differed from those of migrants. Despite these challenges, the respondents found Russia to be a more tolerant country than their home countries and benefited from migration in terms of possibilities to express their gender identity and earn higher income. The discussion section uses these data to compare transition in the sex/gender and geographical spaces.
Notes on the general relativistic viscous ringed disk evolution
Authors: Pugliese D , Stuchlík Z , Karas V
Published: September 2024

A ringed accretion disk (RAD) models a cluster of axi-symmetric co-rotating and/or counter-rotating tori orbiting in the equatorial plane of a central Kerr super-massive Black Hole. We discuss the time evolution of such a ringed disk within the general relativity framework. Our analysis presents a study of the evolving RAD properties using a thin-disk scheme and solving a diffusion-like evolution equation for a RAD in the Kerr spacetime. In the first stage of evolution there is the inter–disk interaction where the individual rings spread inwardly and outwardly, levelling the structure and forming a single distribution with maximum density determined by the initial spread of the component rings. Timescales are dependent on viscosity prescriptions. The early time luminosity, dominated by the dynamics of the inner ringed structure, shows a clear mark of the inner ringed structure. The RAD eventually reaches a single disk phase, building accretion to the inner edge regulated by the inner edge boundary conditions. The late–time luminosity associated to the ringed disk follows a power law decline for the final single disk. In the sideline of this analysis we also considered a modified prescription mimicking an effective turbulent viscosity in the early phases of the rings evolutions.