bluuebunny/crossref_metadata_2025 huggingface dataset:
The social construction of childhood: is a minimum age of marriage attainable in plural societies?
Authors: Ada Tchoukou Julie
Published: September 2024

This paper explores the way in which childhood is socially constructed in the context of child marriage regulation. Despite extreme social and cultural diversity, there is a core ideology in UN human rights instruments, around which official versions of childhood pivot. International law recommends setting the minimum age of marriage at 18years. This article problematizes the progressively depoliticizing effects of a seemingly neutral regulatory drive at the heart of the UN’s promotion of a standardized construction of childhood. The immediate purpose of this article is not to offer solutions to child marriage, but to bring together some elements that may form a basis for understanding the way in which conceptions of childhood are contextually constructed. My hope is that a familiarity with these social perceptions will help to explain the present struggle and resistance to apply universal rights constructions of childhood to non-western societies.
A 3.3‐Million‐Year Record of Antarctic Iceberg Rafted Debris and Ice Sheet Evolution Quantified by Machine Learning
Authors: Jasper Claire E. , Dyer Blake , Reilly Brendan T. , Williams Trevor , Hemming Sidney , Raymo Maureen E.
Published: September 2024

Over the last 3.3 million years, the Antarctic Ice Sheet (AIS) has undergone phases of ice sheet growth and decay, impacting sea level and climate globally. Presently, the largely marine‐terminating AIS loses mass primarily by iceberg calving and basal melt of ice shelves. Quantifying past rates and timing of AIS melt is vital to understanding future cryosphere and sea level changes. One proxy for past ice sheet instabilities is iceberg rafted debris (IRD) fluxes. However, traditional methods of IRD quantification are labor‐intensive. Here, we present a new method of identifying IRD grains in sediment core X‐ray images using a convolutional neural network machine learning algorithm. We present a 3.3‐million‐year record of AIS IRD melt events using sediment cores from International Ocean Discovery Program Sites U1536, U1537, and U1538 in the Southern Ocean's “Iceberg Alley.” We identify two increases in the IRD fluxes throughout this period, at ∼1.8 and 0.43 Ma. We propose that after 1.8 Ma, the AIS expanded and transitioned from a primarily terrestrial‐terminating to a primarily marine‐terminating ice sheet. Therefore, after 1.8 Ma, glacial terminations and AIS iceberg discharge are associated with variations in global ice volume, presumably through the mechanism of sea level and, therefore, grounding line change. The second AIS regime change occurs during the Mid‐Brunhes Event (∼0.43 Ma). After this time, there are heightened and continuous IRD fluxes at each glacial termination, indicating increased AIS size and instability after this time.
Ultrafast near-infrared pyroelectric detector based on inhomogeneous plasmonic metasurface
Authors: Lu Youyan , Liu Liyun , Gao Ruoqian , Xiong Ying , Sun Peiqing , Wu Zhanghao , Wu Kai , Yu Tong , Zhang Kai , Zhang Cheng , Bourouina Tarik , Li Xiaofeng , Liu Xiaoyi
Published: September 2024

Pyroelectric (PE) detection technologies have attracted extensive attention due to the cooling-free, bias-free, and broadband properties. However, the PE signals are generated by the continuous energy conversion processes from light, heat, to electricity, normally leading to very slow response speeds. Herein, we design and fabricate a PE detector which shows extremely fast response in near-infrared (NIR) band by combining with the inhomogeneous plasmonic metasurface. The plasmonic effect dramatically accelerates the light-heat conversion process, unprecedentedly improving the NIR response speed by 2−4 orders of magnitude to 22 μs, faster than any reported infrared (IR) PE detector. We also innovatively introduce the concept of time resolution into the field of PE detection, which represents the detector’s ability to distinguish multiple fast-moving targets. Furthermore, the spatially inhomogeneous design overcomes the traditional narrowband constraint of plasmonic systems and thus ensures a wideband response from visible to NIR. This study provides a promising approach to develop next-generation IR PE detectors with ultrafast and broadband responses.
Sub-picosecond, strain-tunable, polarization-selective optical switching via anisotropic exciton dynamics in quasi-1D ZrSe3
Authors: Suk Sang Ho , Nah Sanghee , Sajjad Muhammad , Seo Sung Bok , Chen Jianxiang , Sim Sangwan
Published: September 2024

In cutting-edge optical technologies, polarization is a key for encoding and transmitting vast information, highlighting the importance of selectively switching and modulating polarized light. Recently, anisotropic two-dimensional materials have emerged for ultrafast switching of polarization-multiplexed optical signals, but face challenges with low polarization ratios and limited spectral ranges. Here, we apply strain to quasi-one-dimensional layered ZrSe3 to enhance polarization selectivity and tune operational energies in ultrafast all-optical switching. Initially, transient absorption on unstrained ZrSe3 reveals a sub-picosecond switching response in polarization along a specific crystal axis, attributed to shifting-recovery dynamics of an anisotropic exciton. However, its polarization selectivity is weakened by a slow non-excitonic response in the perpendicular polarization. To overcome this limitation, we apply strain to ZrSe3 by bending its flexible substrate. The compressive strain spectrally decouples the excitonic and non-excitonic components, doubling the polarization selectivity of the sub-picosecond switching and tripling it compared to that in the tensile-strained ZrSe3. It also effectively tunes the switching energy at a shift rate of ~93 meV %-1. This strain-tunable switching is repeatable, reversible, and robustly maintains the sub-picosecond operation. First-principles calculations reveal that the strain control is enabled by momentum- and band-dependent modulations of the electronic band structure, causing opposite shifts in the excitonic and non-excitonic transitions. Our findings offer a novel approach for high-performance, wavelength-tunable, polarization-selective ultrafast optical switching.
A systematic review of deep brain stimulation for substance use disorders
Authors: Zammit Dimech David , Zammit Dimech Audrey-Ann , Hughes Mark , Zrinzo Ludvic
Published: September 2024

Background

Pharmaco-psychiatric techniques remain the mainstay, first line treatments in substance use disorders (SUD), assisting in detoxification but largely ineffective at reducing dependence. The path to rehabilitation and freedom from addiction often proves uncertain and laborious for both patients and their significant others. Relapse rates for multiple substances of abuse are considerable and the number of SUD patients is on the increase worldwide.

Objective

To assess efficacy of deep brain stimulation (DBS) as a therapeutic solution for SUDs.

Methods

A systematic electronic database search of PubMed and EMBASE retrieved DBS addiction-focused studies on humans, of which a total of 26 (n = 71) from 2007 to 2023 were deemed eligible, including the first randomized controlled trial (RCT) in this field. This review was prospectively registered with PROSPERO: CRD42023411631.

Results

In addressing SUDs, DBS targeting primarily the nucleus accumbens (NAcc), with or without the anterior limb of the internal capsule, presented encouraging levels of efficacy in reducing cravings and consumption, followed by remission in some subjects, but still reporting relapses in 73.2% of patients.

Conclusions

For treatment-refractory addictions DBS use seems limited to reducing cravings with a satisfactory degree of success, yet not clinically consistent in inducing abstinence, suggesting involvement of factors unaffected by DBS intervention. Furthermore, costs and the scale of the problem are such that DBS is unlikely to have a significant societal impact. Nevertheless, DBS may provide insight into the biology of addiction and is worthy of further research using increased methodological rigor, standardized outcome measures, and pre-established surgical protocols.
Insights into phosphoethanolamine cellulose synthesis and secretion across the Gram-negative cell envelope
Authors: Verma Preeti , Ho Ruoya , Chambers Schuyler A. , Cegelski Lynette , Zimmer Jochen
Published: September 2024

Phosphoethanolamine (pEtN) cellulose is a naturally occurring modified cellulose produced by several Enterobacteriaceae. The minimal components of the E. coli cellulose synthase complex include the catalytically active BcsA enzyme, a hexameric semicircle of the periplasmic BcsB protein, and the outer membrane (OM)-integrated BcsC subunit containing periplasmic tetratricopeptide repeats (TPR). Additional subunits include BcsG, a membrane-anchored periplasmic pEtN transferase associated with BcsA, and BcsZ, a periplasmic cellulase of unknown biological function. While cellulose synthesis and translocation by BcsA are well described, little is known about its pEtN modification and translocation across the cell envelope. We show that the N-terminal cytosolic domain of BcsA positions three BcsG copies near the nascent cellulose polymer. Further, the semicircle’s terminal BcsB subunit tethers the N-terminus of a single BcsC protein in a trans-envelope secretion system. BcsC’s TPR motifs bind a putative cello-oligosaccharide near the entrance to its OM pore. Additionally, we show that only the hydrolytic activity of BcsZ but not the subunit itself is necessary for cellulose secretion, suggesting a secretion mechanism based on enzymatic removal of translocation incompetent cellulose. Lastly, protein engineering introduces cellulose pEtN modification in orthogonal cellulose biosynthetic systems. These findings advance our understanding of pEtN cellulose modification and secretion.
Recipient tissue microenvironment determines developmental path of intestinal innate lymphoid progenitors
Authors: Clark Paula A. , Gogoi Mayuri , Rodriguez-Rodriguez Noe , Ferreira Ana C. F. , Murphy Jane E. , Walker Jennifer A. , Crisp Alastair , Jolin Helen E. , Shields Jacqueline D. , McKenzie Andrew N. J.
Published: September 2024

Innate lymphoid cells (ILCs) are critical in maintaining tissue homeostasis, and during infection and inflammation. Here we identify, by using combinatorial reporter mice, a rare ILC progenitor (ILCP) population, resident to the small intestinal lamina propria (siLP) in adult mice. Transfer of siLP-ILCP into recipients generates group 1 ILCs (including ILC1 and NK cells), ILC2s and ILC3s within the intestinal microenvironment, but almost exclusively group 1 ILCs in the liver, lung and spleen. Single cell gene expression analysis and high dimensional spectral cytometry analysis of the siLP-ILCPs and ILC progeny indicate that the phenotype of the group 1 ILC progeny is also influenced by the tissue microenvironment. Thus, a local pool of siLP-ILCP can contribute to pan-ILC generation in the intestinal microenvironment but has more restricted potential in other tissues, with a greater propensity than bone marrow-derived ILCPs to favour ILC1 and ILC3 production. Therefore, ILCP potential is influenced by both tissue of origin and the microenvironment during development. This may provide additional flexibility during the tuning of immune reactions.
Cell swelling enhances ligand-driven β-adrenergic signaling
Authors: Sirbu Alexei , Bathe-Peters Marc , Kumar Jothi L. M. , Inoue Asuka , Lohse Martin J. , Annibale Paolo
Published: September 2024

G protein-coupled receptors’ conformational landscape can be affected by their local, microscopic interactions within the cell plasma membrane. We employ here a pleiotropic stimulus, namely osmotic swelling, to alter the cortical environment within intact cells and monitor the response in terms of receptor function and downstream signaling. We observe that in osmotically swollen cells the β2-adrenergic receptor, a prototypical GPCR, favors an active conformation, resulting in cAMP transient responses to adrenergic stimulation that have increased amplitude. The results are validated in primary cell types such as adult cardiomyocytes, a model system where swelling occurs upon ischemia-reperfusion injury. Our results suggest that receptors’ function is finely modulated by their biophysical context, and specifically that osmotic swelling acts as a potentiator of downstream signaling, not only for the β2-adrenergic receptor, but also for other receptors, hinting at a more general regulatory mechanism.
Thermodynamic evaluation of the aerial and aqueous oxidation of Al – Mg, Al – Si and Al – Mg – Si system alloys at 298 K
Authors: Nikolaychuk Pavel Anatolyevich , Kozeschnik Ernst
Published: September 2024

Aluminum and magnesium are the lightest structural metals, and therefore, various alloys based on them are widely used in both, automotive and aerospace industries. However, aluminum and magnesium are very easily affected by atmospheric and aqueous corrosion, and, therefore, the alloying elements should enhance their corrosion stability. In this work, the thermodynamic analysis of phase and chemical equilibria involving aluminum and magnesium alloys doped with silicon in oxygen–containing air environments, as well as the analysis of chemical and electrochemical equilibria involving these alloys in aqueous environments is conducted. The phase and chemical equiliibria in the Al–Mg, Al–Si, Mg–Si, and Al–Mg–Si systems at 298 K are considered, and the thermodynamic activities of the components of common Al–Mg–Si system alloys are calculated. The invariant chemical equilibria in the systems Al–Mg–O, Al–Si–O, Mg–Si–O at 298 K are considered, the isothermal section of the state diagrams of these systems are plotted, and the oxidation scheme of the Al–Mg–Si system alloys in excess oxygen is proposed. The chemical and electrochemical equilibria in the Al–Mg–Si–H2O system at 298 K are considered and presented in form of the activity – pH and the potential – pH diagrams, and the oxidation of the Al–Mg–Si system alloys in aqueous environments is discussed.
Clinical reasoning amongst paramedics using nebulised β₂ agonists to treat acute asthma exacerbations: a qualitative study
Authors: Mortimer Craig , Nikoletou Dimitra , Ooms Ann , Williams Julia
Published: September 2024

The heterogeneous nature of asthma results in a wide range of presentations during exacerbation. Despite UK pre-hospital management guidelines focusing on β₂ agonists, variables such as cause, severity, underlying health, comorbidities, and drug side effects can often make emergency treatment optimisation difficult. This article examines paramedics’ methods of observing, perceiving, interpreting, and treating asthma with β₂ agonists, often acting on limited information in rapidly evolving situations. We recruited paramedics from a single UK National Health Service ambulance Trust for qualitative semi-structured interviews. Responses underwent framework analysis to identify data similarities and differences. Fifteen qualitative interviews with paramedics revealed three main themes affecting patient management: clinician experience of presentation, adaptation of patient management approaches, and severity of side effects. Paramedics felt their ability to manage various asthma presentations was enhanced through guideline adaptation based on their own clinical experience and understanding of β₂ agonist side effects, allowing tailored responses based on a set of reinforcing factors. Inductive analysis revealed additional complexities within these themes, such as anxiety and diabetes, which may influence β₂ agonist administration and result in multiple care pathways being initiated during exacerbation. Paramedic care mirrors asthma’s complexity, accounting for a range of characteristics. A dynamic, critically thought approach enables patient management to be based on the presenting conditions rather than strict adherence to a single algorithm. Comprehending the complexities and variables in treatment can be crucial to how paramedics rationalise their treatment and optimise the care provided.
An ecological approach to understanding transitions and tensions in complex learning contexts
Authors: McCrone Luke , Kingsbury Martyn
Published: September 2024

The move away from transmission-based lecturing toward a more student-centred active learning approach is well evidenced in STEM higher education. However, the examination of active learning has generally remained confined to formal timetabled contexts, with assumptions made that students independently manage the transition between timetabled and non-timetabled learning. This paper introduces research findings from a mixed methods study that used an ecological approach when investigating student transitions between a formal lecture theatre and adjacent informal breakout space in a UK STEM university. Using quantitative occupancy monitoring data to analyse usage patterns of both spaces, in combination with qualitative ethnographic observations and field interviews, permitted a purposeful exploration of student engagement with transitions within and between the two learning spaces. The ecological approach aided the discovery of spatial, pedagogic and agentic transitions and tensions, which subsequently informed strategic modification of space across the institution to facilitate the adoption of active learning pedagogy.
An intranuclear bacterial parasite of deep-sea mussels expresses apoptosis inhibitors acquired from its host
Authors: Porras Miguel Ángel González , Assié Adrien , Tietjen Målin , Violette Marlene , Kleiner Manuel , Gruber-Vodicka Harald , Dubilier Nicole , Leisch Nikolaus
Published: September 2024

A limited number of bacteria are able to colonize the nuclei of eukaryotes. ‘Candidatus Endonucleobacter’ infects the nuclei of deep-sea mussels, where it replicates to ≥80,000 bacteria per nucleus and causes nuclei to swell to 50 times their original size. How these parasites are able to replicate and avoid apoptosis is not known. Dual RNA-sequencing transcriptomes of infected nuclei isolated using laser-capture microdissection revealed that ‘Candidatus Endonucleobacter’ does not obtain most of its nutrition from nuclear DNA or RNA. Instead, ‘Candidatus Endonucleobacter’ upregulates genes for importing and digesting sugars, lipids, amino acids and possibly mucin from its host. It likely prevents apoptosis of host cells by upregulating 7–13 inhibitors of apoptosis, proteins not previously seen in bacteria. Comparative phylogenetic analyses revealed that ‘Ca. Endonucleobacter’ acquired inhibitors of apoptosis through horizontal gene transfer from their hosts. Horizontal gene transfer from eukaryotes to bacteria is assumed to be rare, but may be more common than currently recognized.
Sub-attosecond-precision optical-waveform stability measurements using electro-optic sampling
Authors: Hussain Syed A. , Hofer Christina , Högner Maximilian , Schweinberger Wolfgang , Buberl Theresa , Bausch Daniel , Huber Marinus , Krausz Ferenc , Pupeza Ioachim
Published: September 2024

The generation of laser pulses with controlled optical waveforms, and their measurement, lie at the heart of both time-domain and frequency-domain precision metrology. Here, we obtain mid-infrared waves via intra-pulse difference-frequency generation (IPDFG) driven by 16-femtosecond near-infrared pulses, and characterise the jitter of sub-cycle fractions of these waves relative to the gate pulses using electro-optic sampling (EOS). We demonstrate sub-attosecond temporal jitter at individual zero-crossings and sub-0.1%-level relative amplitude fluctuations in the 10-kHz–0.625-MHz band. Chirping the nearly-octave-spanning mid-infrared pulses uncovers wavelength-dependent attosecond-scale waveform jitter. Our study validates EOS as a broadband (both in the radio-frequency and the optical domains), highly sensitive measurement technique for the jitter dynamics of optical waveforms. This sensitivity reveals outstanding stability of the waveforms obtained via IPDFG and EOS, directly benefiting precision measurements including linear and nonlinear (infrared) field-resolved spectroscopy. Furthermore, these results form the basis toward EOS-based active waveform stabilisation and sub-attosecond multi-oscillator synchronisation/delay tracking.
Genetic polymorphisms in FABP2, CYP2E1, and TP53 genes are potentially associated with colorectal cancer susceptibility
Authors: Ijaz Maryam , Chen Chien-Chin , Iqbal Rana Khalid , Farooq Hafiza Aneela , Mehmood Rubaida , Asif Muhammad , Akbar Atif , Khan Adil , Ijaz Waseem , Said Mourad Ben , Wondmie Gezahign Fentahun , Ibenmoussa Samir , Okla Mohammad K. , Iqbal Furhan
Published: September 2024

Colorectal cancer (CRC) is among the most prevalent cancers with a high mortality rate. Both genetic and environmental factors contribute to CRC development. This study aimed to assess the association of single nucleotide polymorphisms (SNPs) in the fatty acid binding protein-2 (rs1799883), Cytochrome P450 2E1 (rs3813865), TP53 (rs1042522), and Murine double minute 2 (rs1042522) genes with CRC. A cross-sectional case–control study was conducted at the Institute of Molecular Biology and Biotechnology from May 2020 to March 2021, involving CRC patients (N = 100) and controls (N = 100) recruited from the Multan district in Pakistan. Polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) and tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) were employed to investigate the studied SNPs. The association of SNPs in all genes with CRC was examined either individually or in various combinations. Genotypes at three SNPs, rs1799883 in FABP2, rs3813865 in CYP2E1, and rs1042522 in TP53, were found to be associated with the development of CRC, while rs1042522 in MDM2 was not. Patients who were married, smoked, lacked exercise habits or had a family history of CRC were at a greater risk of acquiring the disease. FABP2 gene rs1799883, CYP2E1 gene rs3813865, and TP53 gene rs1042522 polymorphisms are significant in the development of CRC in Pakistani participants.
TAK-861, a potent, orally available orexin receptor 2-selective agonist, produces wakefulness in monkeys and improves narcolepsy-like phenotypes in mouse models
Authors: Mitsukawa Kayo , Terada Michiko , Yamada Ryuji , Monjo Taku , Hiyoshi Tetsuaki , Nakakariya Masanori , Kajita Yuichi , Ando Tatsuya , Koike Tatsuki , Kimura Haruhide
Published: September 2024

Narcolepsy type 1 (NT1) is associated with severe loss of orexin neurons and characterized by symptoms including excessive daytime sleepiness and cataplexy. Current medications indicated for NT1 often show limited efficacy, not addressing the full spectrum of symptoms, demonstrating a need for novel drugs. We discovered a parenteral orexin receptor 2 (OX2R) agonist, danavorexton, and an orally available OX2R agonist, TAK-994; both improving NT1 phenotypes in mouse models and individuals with NT1. However, danavorexton has limited oral availability and TAK-994 has a risk of off-target liver toxicity. To avoid off-target-based adverse events, a highly potent molecule with low effective dose is preferred. Here, we show that a novel OX2R-selective agonist, TAK-861 [N-{(2S,3R)-4,4-Difluoro-1-(2-hydroxy-2-methylpropanoyl)-2-[(2,3′,5′-trifluoro[1,1′-biphenyl]-3-yl)methyl]pyrrolidin-3-yl}ethanesulfonamide], activates OX2R with a half-maximal effective concentration of 2.5 nM and promotes wakefulness at 1 mg/kg in mice and monkeys, suggesting ~ tenfold higher potency and lower effective dosage than TAK-994. Similar to TAK-994, TAK-861 substantially ameliorates wakefulness fragmentation and cataplexy-like episodes in orexin/ataxin-3 and orexin-tTA;TetO DTA mice (NT1 mouse models). Compared with modafinil, TAK-861 induces highly correlated brain-wide neuronal activation in orexin-tTA;TetO DTA mice, suggesting efficient wake-promoting effects. Thus, TAK-861 has potential as an effective treatment for individuals with hypersomnia disorders including narcolepsy, potentially with a favorable safety profile.
Biomechanical evaluation of an experimental internal ring fixator (RingFix) for stabilization of pelvic ring injuries on an osteoporotic bone model
Authors: Arand Charlotte , Hartung Christian , Mehler Dorothea , Gercek Erol , Wollstädter Jochen , Wagner Daniel , Rommens Pol M.
Published: September 2024

During the last decades, effective pain reduction and early mobilization were identified as the central priorities in therapy of insufficiency fractures of the pelvis. For operative treatment minimally-invasive stabilization techniques are favored. While there is consensus on the significance of sufficient dorsal stabilization the role of additional fixation of the anterior fracture component stays under discussion. Within the present study we developed an internal ring fixator system (RingFix) with the question whether an in-itself-closed construct can improve stability of the entire ring structure. RingFix was evaluated on an osteoporotic bone model with a standardized FFP IIIc fracture within an established biomechanical setup regarding its primary stabilization potential. Further, it was compared to transiliac–transsacral screw fixation with and without stabilization of the anterior fracture component. The transiliac–transsacral fixation with separate screw fixation of the anterior fracture showed significantly higher stability than the RingFix and the transiliac–transsacral screw fixation without anterior stabilization. Our results show that stabilization of the anterior fracture component relevantly improves the stability of the entire ring construct. As a bridging stabilizer, RingFix shows biomechanical advantages over an isolated dorsal fracture fixation, but inferior results than direct stabilization of the single fracture components.
mTORC1 pathway activity biases cell fate choice
Authors: Wang Yuntao , Papayova Monika , Warren Eleanor , Pears Catherine J.
Published: September 2024

Pluripotent stem cells can differentiate into distinct cell types but the intracellular pathways controlling cell fate choice are not well understood. The social amoeba Dictyostelium discoideum is a simplified system to study choice preference as proliferating amoebae enter a developmental cycle upon starvation and differentiate into two major cell types, stalk and spores, organised in a multicellular fruiting body. Factors such as acidic vesicle pH predispose amoebae to one fate. Here we show that the mechanistic target of rapamycin complex 1 (mTORC1) pathway has a role in cell fate bias in Dictyostelium. Inhibiting the mTORC1 pathway activity by disruption of Rheb (activator Ras homolog enriched in brain), or treatment with the mTORC1 inhibitor rapamycin prior to development, biases cells to a spore cell fate. Conversely activation of the pathway favours stalk cell differentiation. The Set1 histone methyltransferase, responsible for histone H3 lysine4 methylation, in Dictyostelium cells regulates transcription at the onset of development. Disruption of Set1 leads to high mTORC1 pathway activity and stalk cell predisposition. The ability of the mTORC1 pathway to regulate cell fate bias of cells undergoing differentiation offers a potential target to increase the efficiency of stem cell differentiation into a particular cell type.
Pregnancy-related changes in the canine serum N-glycosylation pattern studied by Rapifluor HILIC-UPLC-FLR-MS
Authors: Ramström Margareta , Lavén Martin , Amini Ahmad , Holst Bodil Ström
Published: September 2024

Canine reproduction differs from that of many other domestic animals, and increased knowledge on biochemical changes during canine pregnancy is important for investigations of infertility or subfertility. The total glycosylation pattern, i.e., the glycome, of body fluids reflects cellular status in health and disease. The aim of the present pilot study was to investigate pregnancy-related changes of the serum N-glycome in bitches. A method based on Rapifluor HILIC-UPLC-FLR-MS was optimized and applied for analysis and quantification of N-glycans in canine serum. Serum samples from six pregnant and five non-pregnant bitches, collected at four well-defined time points, were included. The levels of sialylated and galactosylated complex glycans were significantly elevated in serum from pregnant bitches, consistent with previous reports on human pregnancy. The levels of fucosylated and agalactosylated glycans decreased significantly in pregnant dogs. In non-pregnant dogs, the glycosylation pattern did not change during the cycle. Pregnancy is an inflammatory state, but our findings during canine pregnancy are quite the opposite to changes that have previously been described for dogs with a known parasitic infection. Evaluation of the canine glycome may thus be valuable in studies of canine pregnancy, possibly differing inflammatory changes related to pregnancy to those caused by an infection.
Self-supervised learning of wrist-worn daily living accelerometer data improves the automated detection of gait in older adults
Authors: Brand Yonatan E. , Kluge Felix , Palmerini Luca , Paraschiv-Ionescu Anisoara , Becker Clemens , Cereatti Andrea , Maetzler Walter , Sharrack Basil , Vereijken Beatrix , Yarnall Alison J. , Rochester Lynn , Del Din Silvia , Muller Arne , Buchman Aron S. , Hausdorff Jeffrey M. , Perlman Or
Published: September 2024

Progressive gait impairment is common among aging adults. Remote phenotyping of gait during daily living has the potential to quantify gait alterations and evaluate the effects of interventions that may prevent disability in the aging population. Here, we developed ElderNet, a self-supervised learning model for gait detection from wrist-worn accelerometer data. Validation involved two diverse cohorts, including over 1000 participants without gait labels, as well as 83 participants with labeled data: older adults with Parkinson's disease, proximal femoral fracture, chronic obstructive pulmonary disease, congestive heart failure, and healthy adults. ElderNet presented high accuracy (96.43 ± 2.27), specificity (98.87 ± 2.15), recall (82.32 ± 11.37), precision (86.69 ± 17.61), and F1 score (82.92 ± 13.39). The suggested method yielded superior performance compared to two state-of-the-art gait detection algorithms, with improved accuracy and F1 score (p < 0.05). In an initial evaluation of construct validity, ElderNet identified differences in estimated daily walking durations across cohorts with different clinical characteristics, such as mobility disability (p < 0.001) and parkinsonism (p < 0.001). The proposed self-supervised method has the potential to serve as a valuable tool for remote phenotyping of gait function during daily living in aging adults, even among those with gait impairments.
A hybrid residue based sequential encoding mechanism with XGBoost improved ensemble model for identifying 5-hydroxymethylcytosine modifications
Authors: Uddin Islam , Awan Hamid Hussain , Khalid Majdi , Khan Salman , Akbar Shahid , Sarker Mahidur R. , Abdolrasol Maher G. M. , Alghamdi Thamer A. H.
Published: September 2024

RNA modifications play an important role in actively controlling recently created formation in cellular regulation mechanisms, which link them to gene expression and protein. The RNA modifications have numerous alterations, presenting broad glimpses of RNA’s operations and character. The modification process by the TET enzyme oxidation is the crucial change associated with cytosine hydroxymethylation. The effect of CR is an alteration in specific biochemical ways of the organism, such as gene expression and epigenetic alterations. Traditional laboratory systems that identify 5-hydroxymethylcytosine (5hmC) samples are expensive and time-consuming compared to other methods. To address this challenge, the paper proposed XGB5hmC, a machine learning algorithm based on a robust gradient boosting algorithm (XGBoost), with different residue based formulation methods to identify 5hmC samples. Their results were amalgamated, and six different frequency residue based encoding features were fused to form a hybrid vector in order to enhance model discrimination capabilities. In addition, the proposed model incorporates SHAP (Shapley Additive Explanations) based feature selection to demonstrate model interpretability by highlighting the high contributory features. Among the applied machine learning algorithms, the XGBoost ensemble model using the tenfold cross-validation test achieved improved results than existing state-of-the-art models. Our model reported an accuracy of 89.97%, sensitivity of 87.78%, specificity of 94.45%, F1-score of 0.8934%, and MCC of 0.8764%. This study highlights the potential to provide valuable insights for enhancing medical assessment and treatment protocols, representing a significant advancement in RNA modification analysis.
Using the online version of the Trier Social Stress Test to investigate the effect of acute stress on functional lateralization
Authors: Pfeifer Lena Sophie , Heyers Katrin , Wolf Oliver T. , Stockhorst Ursula , Güntürkün Onur , Merz Christian J. , Ocklenburg Sebastian
Published: September 2024

How stress affects functional hemispheric asymmetries is relevant because stress represents a risk factor for the development of mental disorders and various mental disorders are associated with atypical lateralization. Using three lateralization tasks, we investigated whether functional hemispheric asymmetries in the form of hemispheric dominance for language (verbal dichotic listening task), emotion processing (emotional dichotic listening task), and visuo-spatial attention (line bisection task) were affected by acute stress in healthy adults. One hundred twenty right-handed men and women performed these lateralization tasks in randomized order after exposure to a mild online stressor (i.e., an online variant of the Trier Social Stress Test (TSST), TSST-OL) and a non-stressful online control task (friendly TSST-OL, fTSST-OL) in a within-subjects design. Importantly, the verbal and the emotional dichotic listening tasks were presented online whereas the line bisection task was completed in paper–pencil form. During these tasks, we found the expected hemispheric asymmetries, indicating that online versions of both the verbal and the emotional dichotic listening task can be used to measure functional hemispheric asymmetries in language and emotion processing remotely. Even though subjective and physiological markers confirmed the success of the online stress manipulation, replicating previous studies, we found no stress-induced effect on functional hemispheric asymmetries. Thus, in healthy participants, functional hemispheric asymmetries do not seem to change flexibly in response to acute stress.
Glycomics of cervicovaginal fluid from women at risk of preterm birth reveals immuno-regulatory epitopes that are hallmarks of cancer and viral glycosylation
Authors: Wu Gang , Grassi Paola , Molina Belen Gimeno , MacIntyre David A. , Sykes Lynne , Bennett Phillip R. , Dell Anne , Haslam Stuart M.
Published: September 2024

During pregnancy the immune system needs to maintain immune tolerance of the foetus while also responding to infection, which can cause premature activation of the inflammatory pathways leading to the onset of labour and preterm birth. The vaginal microbiome is an important modifier of preterm birth risk, with Lactobacillus dominance during pregnancy associated with term delivery while high microbial diversity is associated with an increased risk of preterm birth. Glycans on glycoproteins along the lower female reproductive tract are fundamental to microbiota-host interactions and the mediation of inflammatory responses. However, the specific glycan epitopes involved in these processes are not well understood. To address this, we conducted glycomic analyses of cervicovaginal fluid (CVF) from 36 pregnant women at high risk of preterm birth and 4 non-pregnant women. Our analysis of N- and O-glycans revealed a rich CVF glycome. While O-glycans were shown to be the main carriers of ABO blood group epitopes, the main features of N-glycans were the presence of abundant paucimannose and high mannose glycans, and a remarkable diversity of complex bi-, tri-, and tetra-antennary glycans decorated with fucose and sialic acid. We identified immuno-regulatory epitopes, such as Lewis antigens, and found that fucosylation was negatively correlated to pro-inflammatory factors, such as IL-1β, MMP-8, C3a and C5a, while glycans with only sialylated antennae were mainly positively correlated to those. Similarly, paucimannose glycans showed a positive correlation to pro-inflammatory factors. We revealed a high abundance of glycans which have previously been identified as hallmarks of cancer and viral glycosylation, such as Man8 and Man9 high mannose glycans. Although each pregnant woman had a unique glycomic profile, longitudinal studies showed that the main glycosylation features were consistent throughout pregnancy in women who delivered at term, whereas women who experienced extreme preterm birth exhibited sharp changes in the CVF glycome shortly before delivery. These findings shed light on the processes underlying the role of glycosylation in maintaining a healthy vaginal microbiome and associated host immune responses. In addition, these discoveries facilitate our understanding of the lower female reproductive tract which has broad implications for women’s health.
High levels of tumor cell-intrinsic STING signaling are associated with increased infiltration of CD8+ T cells in dMMR/MSI-H gastric cancer
Authors: Kanoda Ryo , Nakajima Shotaro , Fukai Satoshi , Saito Motonobu , Saito Katsuharu , Suzuki Hiroya , Kikuchi Tomohiro , Nirei Azuma , Okayama Hirokazu , Mimura Kosaku , Hanayama Hiroyuki , Sakamoto Wataru , Momma Tomoyuki , Saze Zenichiro , Kono Koji
Published: September 2024

Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) gastric cancer (GC) exhibits an immune-active tumor microenvironment (TME) compared to MMR proficient (pMMR)/microsatellite stable/Epstein-Barr virus-negative [EBV (−)] GC. The tumor cell-intrinsic cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway has been considered a key regulator of immune cell activation in the TME. However, its significance in regulating the immune-active TME in dMMR/MSI-H GC remains unclear. Here, we demonstrated that tumor cell-intrinsic cGAS–STING was highly expressed in dMMR GC compared to pMMR/EBV (−) GC. The expression of tumor cell-intrinsic STING was significantly and positively associated with the number of CD8+ tumor-infiltrating lymphocytes in GC. Analysis of TCGA datasets revealed that the expression of interferon-stimulated genes and STING downstream T-cell attracting chemokines was significantly higher in MSI-H GC compared to other subtypes of GC with EBV (−). These results suggest that tumor cell-intrinsic STING signaling plays a key role in activating immune cells in the dMMR/MSI-H GC TME and might serve as a novel biomarker predicting the efficacy of immunotherapy for GC treatment.
Inference through innovation processes tested in the authorship attribution task
Authors: Tani Raffaelli Giulio , Lalli Margherita , Tria Francesca
Published: September 2024

Urn models for innovation capture fundamental empirical laws shared by several real-world processes. The so-called urn model with triggering includes, as particular cases, the urn representation of the two-parameter Poisson-Dirichlet process and the Dirichlet process, seminal in Bayesian non-parametric inference. In this work, we leverage this connection to introduce a general approach for quantifying closeness between symbolic sequences and test it within the framework of the authorship attribution problem. The method demonstrates high accuracy when compared to other related methods in different scenarios, featuring a substantial gain in computational efficiency and theoretical transparency. Beyond the practical convenience, this work demonstrates how the recently established connection between urn models and non-parametric Bayesian inference can pave the way for designing more efficient inference methods. In particular, the hybrid approach that we propose allows us to relax the exchangeability hypothesis, which can be particularly relevant for systems exhibiting complex correlation patterns and non-stationary dynamics.
An aza-Diels–Alder approach to nitrogen-containing tetrabenzoacene derivatives
Authors: Peng Ethan R. , Burke Anthony M. , Dibble David J. , KC Chandra B. , Kurakake Reina , Liu Panyiming , Lopez Robert , Dennison Philip R. , Gorodetsky Alon A.
Published: September 2024

We report a general and modular aza-Diels–Alder reaction-based approach to substituted, expanded, functionalized, and dimeric nitrogen-containing tetrabenzoacenes.
A grain-like cerium oxide nanostructure: synthesis and uric acid sensing application
Authors: Ahmad Rafiq , Masrat Sakeena , Rehman Md. Tabish , AlAjmi Mohamed F. , Alam Shamshad , Mishra Prabhash , Lee Byeong-Il
Published: September 2024

Hydrothermally prepared grain-like CeO2 nanostructures were useful for creating a high-performance and non-enzymatic sensor for uric acid detection.
Unlocking the structure and cation synergistic modulation of Prussian blue analogues with double redox mechanism for improved aqueous nonmetallic ion storage
Authors: Fu Hao , Ye Lingqian , Yang Jun
Published: September 2024

The performance of aqueous non-metallic ion batteries can be enhanced by constructing multi-active site PBAs through the synergistic regulation of structure and ions.
Manganese oxide nanoparticles elicit cadmium tolerance in wheat seedlings by ionomic and phenomic adjustment, regulation of AsA–GSH pathway, cellular thickness recovery, and antioxidant modulation
Authors: Anas Muhammad , Bibi Samina , Farwa Ume , Khan Amjid , Quraishi Umar Masood
Published: September 2024

Manganese dioxide nanoparticles decrease Cd uptake and oxidatives, enhancing wheat tolerance and improving crop resilience in contaminated soils.
Apigenin ameliorates lupus nephritis by inhibiting SAT3 signaling in CD8+ T cells
Authors: Liu Jingqun , Wang Nianzhi , Wu Zhenyu , Gan Yihong , Ji Jinjun , Huang Zixuan , Du Yu , Wen Chengping , Tian Fengyuan , Fan Yongsheng , Xu Li
Published: September 2024

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread organ and tissue involvement, with lupus nephritis (LN) being one of its most severe complications.
Understanding the electrochemical behaviour of reduced graphene oxide cathodes in all-carbon Na-ion batteries
Authors: Orzech Marcin W. , Mazzali Francesco , Adomkevicius Arturas , Coduri Mauro , Niu Yubiao , McGettrick James D. , Chater Philip A. , Cabo-Fernandez Laura , Hardwick Laurence J. , Malavasi Lorenzo , Margadonna Serena
Published: September 2024

This work investigates the energy storage mechanism responsible for high capacity and stability of reduced graphene oxide cathodes for sodium-ion batteries.
Effects of metal–metal bonding in photosensitizers: red-shifted absorption and oscillator strength enhancement
Authors: Jinarathne Oshan J. , Karunananda Malkanthi K.
Published: September 2024

Metal–metal bonds facilitate a red-shift in the maximum absorption wavelength and an enhancement of the oscillator strength in photosensitizers.
Dual luminescence and infrared circularly polarized luminescence up to 900 nm with platinum complexes bearing a helical donor–acceptor ligand
Authors: Vázquez-Domínguez Pablo , Horojat Maher , Suits Eva , José Fernández de Córdova Francisco , Vanthuyne Nicolas , Jacquemin Denis , Ros Abel , Favereau Ludovic
Published: September 2024

Engineering the intramolecular charge transfer character of ligands in axially chiral arylisoquinolines platinum(ii) complexes leads to both fluorescence and phosphorescence emissions in solution, with NIR CPL that extends up to almost 850 nm.
A comprehensive study on the halogenation effect of non-fullerene acceptors for photovoltaic application
Authors: Peng Jing , Ma Lijiao , Li Huixue , Wang Guanlin , Chen Zhihao , Chen Feiwu , Hou Jianhui , Zhang Shaoqing
Published: September 2024

Four small-molecule acceptors with the same conjugated backbone but different terminal halogen substituents (F, Cl, Br, I) were developed, the effects of these halogens on film morphology and optoelectronic performance were systematically studied.
Copper-catalyzed remote asymmetric yne-allylic substitution: construction of thiazolone derivatives with adjacent chiral centers
Authors: Wang Zi-Han , Wang Jia-Run , Wei Ying-Ying , Liu Bing , Lin Tao-Yan
Published: September 2024

Herein, we report a highly diastereo- and enantioselective copper-catalyzed remote asymmetric yne-allylic substitution of yne-allylic esters and thiazolones.
Nanostructured layered double hydroxide (NLDH) – Zn/Al-based materials: strategy to improve performance for zirconium sorption from acidic sulfate solution
Authors: Masoud Ahmed M. , Mubark Amal E. , Taha Mohamed H. , Ibrahim Saber
Published: September 2024

Preparation, characterization, and investigation of Zn/Al-NLDH for effective removal of zirconium from aqueous solutions. A successful adsorption Zn/Al-NLDH was approved using TEM and SEM-EDX analyses.
Bioreceptor modified electrochemical biosensors for the detection of life threating pathogenic bacteria: a review
Authors: Khaleque Md. Abdul , Hossain Syed Imdadul , Ali Md. Romzan , Aly Saad Aly Mohamed , Abuelmakarem Hala S. , Al Mamun Muhammad Shamim , Hossain Khan Md. Zaved
Published: September 2024

The lack of reliable and efficient techniques for early monitoring to stop long-term effects on human health is an increasing problem as the pathogenesis effect of infectious bacteria is growing continuously.
New N-phenylpyrrolamide inhibitors of DNA gyrase with improved antibacterial activity
Authors: Cotman Andrej Emanuel , Fulgheri Federica , Piga Martina , Peršolja Peter , Tiz Davide Benedetto , Skok Žiga , Durcik Martina , Sterle Maša , Dernovšek Jaka , Cruz Cristina D. , Tammela Päivi , Szili Petra Éva , Daruka Lejla , Pál Csaba , Zega Anamarija , Mašič Lucija Peterlin , Ilaš Janez , Tomašič Tihomir , Kikelj Danijel , Zidar Nace
Published: September 2024

New N-phenylpyrrolamide inhibitors of DNA gyrase were developed with excellent on-target activity and improved antibacterial activity.
Development of the telescoped flow Pd-catalyzed aerobic alcohol oxidation/reductive amination sequence in the synthesis of new phosphatidylinositide 3-kinase inhibitor (CPL302415)
Authors: Michałek Stanisław , Maj Anna M. , Gurba-Bryśkiewicz Lidia , Maruszak Wioleta , Wiśniewski Krzysztof , Zagozda Marcin , Stypik Mariola , Dubiel Krzysztof , Wieczorek Maciej
Published: September 2024

Development of a telescopic sequence for the last two steps in the CPL302415 synthesis (71.6% total yield). The procedure was generalized into the synthesis of other biologically active PI3Kδ inhibitors based on the pyrazolo[1,5-a]pyrimidine core.
Design, synthesis, and in vitro and in silico study of 1-benzyl-indole hybrid thiosemicarbazones as competitive tyrosinase inhibitors
Authors: Batool Zahra , Ullah Saeed , Khan Ajmal , Siddique Farhan , Nadeem Sumaira , Alshammari Abdulrahman , Albekairi Norah A. , Talib Rimsha , Al-Harrasi Ahmed , Shafiq Zahid
Published: September 2024

Developing new anti-tyrosinase drugs seems crucial for the medical and industrial fields since irregular melanin synthesis is linked to the resurgence of several skin conditions, including melanoma, and the browning of fruits and vegetables.
Facile construction of 2-pyrones under carbene catalysis
Authors: Yu Miao , Huang Jie , Zhu Haibin , Shi Dongping , Yang Weiqi , Liu Yingjie , Ji Yubin , Fu Zhenqian
Published: September 2024

2-Pyrones are valuable structural motifs. This review examines the recent advancements in NHC-catalyzed synthesis of 2-pyrones.
A-site cation manipulation of exemplary second harmonic generation response and optical anisotropy in rare-earth borates
Authors: Song Jie , Zhao Huijian , Li Conggang , Ye Ning , Hu Zhanggui , Wu Yicheng
Published: September 2024

Rare-earth borate compounds, KxNa3−xLa2B3O9 (x = 2–3), were designed by finely tuning the composition of A-site cations.