bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal analysis of circulating tumor cell numbers improves tracking metastatic breast cancer progression
Authors: Szostakowska-Rodzos Malgorzata , Fabisiewicz Anna , Wakula Maciej , Tabor Sylwia , Szafron Lukasz , Jagiello-Gruszfeld Agnieszka , Grzybowska Ewa Anna
Published: June 2024

Hormone-responsive breast cancer represents the most common type and has the best prognosis, but still approximately 40% of patients with this type can develop distant metastases, dramatically worsening the patient’s survival. Monitoring metastatic breast cancer (mBC) for signs of progression is an important part of disease management. Circulating tumor cell (CTC) detection and molecular characteristics gain importance as a diagnostic tool, but do not represent a clinical standard and its value as a predictor of progression is not yet established. The main objective of this study was to estimate the prognostic value of not only the CTC numbers, but also the dynamics of the CTC numbers in the same patient during the continuous evaluation of CTCs in patients with advanced breast cancer. The other objective was to assess the molecular changes in CTCs compared to primary tumor samples by genetic analysis of the seven genes associated with estrogen signaling pathway, mutations in which are often responsible for the resistance to endocrine therapy, and subsequent progression. This approach was taken to evaluate if genetic analysis of CTCs can be used in tracking the resistance, signaling that hormonal therapy should be replaced. Consequently, this report presents the results of a longitudinal CTC study based on three subsequent blood collections from 135 patients with metastatic breast cancer, followed by molecular analysis of the isolated single CTCs. CTCs were detected and isolated using an image-based, EpCAM-independent system CytoTrack; this approach allowed evaluation of EpCAM expression in detected CTCs. Isolated CTCs were subjected to NGS analysis to assess mutational changes. The results confirm the importance of the status of the CTC for progression-free survival and overall survival and provide new data on the dynamics of the CTC during a long monitoring period and in relation to clinical progression, highlighting the advantage of constant monitoring over the single count of CTC. Furthermore, high genetic and phenotypic inter- and intrapatient heterogeneity observed in CTCs suggest that metastatic lesions are divergent. High genetic heterogeneity in the matching CTC/primary tumor samples may indicate early dissemination. The tendency towards the accumulation of activating/oncogenic mutation in CTCs, leading to anti-estrogen resistant disease, was not confirmed in this study.
Prevalence of coronaviruses in European bison (Bison bonasus) in Poland
Authors: Larska Magdalena , Tomana Jarosław , Krzysiak Michał K. , Pomorska-Mól Małgorzata , Socha Wojciech
Published: June 2024

Coronaviruses have been confirmed to infect a variety of species, but only one case of associated winter dysentery of European bison has been described. The study aimed to analyze the prevalence, and define the impact on the species conservation, the source of coronavirus infection, and the role of the European bison in the transmission of the pathogen in Poland. Molecular and serological screening was performed on 409 European bison from 6 free-ranging and 14 captive herds over the period of 6 years (2017–2023). Presence of coronavirus was confirmed in one nasal swab by pancoronavirus RT-PCR and in 3 nasal swab samples by bovine coronavirus (BCoV) specific real time RT-PCR. The detected virus showed high (> 98%) homology in both RdRp and Spike genes to BCoV strains characterised recently in Polish cattle and strains isolated from wild cervids in Italy. Antibodies specific to BCoV were found in 6.4% of tested samples, all originating from free-ranging animals. Seroprevalence was higher in adult animals over 5 years of age (p = 0.0015) and in females (p = 0.09). Our results suggest that European bison play only a limited role as reservoirs of bovine-like coronaviruses. Although the most probable source of infections in the European bison population in Poland is cattle, other wild ruminants could also be involved. In addition, the zoonotic potential of bovine coronaviruses is quite low.
Stochastic circular persistent currents of exciton polaritons
Authors: Barrat J. , Cherbunin Roman , Sedov Evgeny , Aladinskaia Ekaterina , Liubomirov Alexey , Litvyak Valentina , Petrov Mikhail , Zhou Xiaoqing , Hatzopoulos Z. , Kavokin Alexey , Savvidis P. G.
Published: June 2024

We monitor the orbital degree of freedom of exciton-polariton condensates confined within an optical trap and unveil the stochastic switching of persistent annular polariton currents under pulse-periodic excitation. Within an elliptical trap, the low-lying in energy polariton current states manifest as a two-petaled density distribution with a swirling phase. In the stochastic regime, the density distribution, averaged over multiple excitation pulses, becomes homogenized in the azimuthal direction. Meanwhile, the weighted phase, extracted from interference experiments, exhibits two compensatory jumps when varied around the center of the trap. Introducing a supplemental control optical pulse to break the reciprocity of the system enables the transition from a stochastic to a deterministic regime, allowing for controlled polariton circulation direction.
Highly inclined light sheet allows volumetric super-resolution imaging of efflux pumps distribution in bacterial biofilms
Authors: Vignolini T. , Capitanio M. , Caldini C. , Gardini L. , Pavone F. S.
Published: June 2024

Bacterial biofilms are highly complex communities in which isogenic bacteria display different gene expression patterns and organize in a three-dimensional mesh gaining enhanced resistance to biocides. The molecular mechanisms behind such increased resistance remain mostly unknown, also because of the technical difficulties in biofilm investigation at the sub-cellular and molecular level. In this work we focus on the AcrAB-TolC protein complex, a multidrug efflux pump found in Enterobacteriaceae, whose overexpression is associated with most multiple drug resistance (MDR) phenotypes occurring in Gram-negative bacteria. We propose an optical method to quantify the expression level of the AcrAB-TolC pump within the biofilm volume at the sub-cellular level, with single-molecule sensitivity. Through a combination of super-resolution PALM with single objective light sheet and precision genome editing, we can directly quantify the spatial distribution of endogenous AcrAB-TolC pumps expressed in both planktonic bacteria and, importantly, within the bacterial biofilm volume. We observe a gradient of pump density within the biofilm volume and over the course of biofilm maturation. Notably, we propose an optical method that could be broadly employed to achieve volumetric super-resolution imaging of thick samples.
Azathioprine promotes intestinal epithelial cell differentiation into Paneth cells and alleviates ileal Crohn’s disease severity
Authors: Ragab Mohab , Schlichting Heidi , Hicken Maren , Mester Patricia , Hirose Misa , Almeida Larissa N. , Christiansen Lea , Ibrahim Saleh , Tews Hauke Christian , Divanovic Senad , Sina Christian , Derer Stefanie
Published: June 2024

Paneth cells (PCs), a subset of intestinal epithelial cells (IECs) found at the base of small intestinal crypts, play an essential role in maintaining intestinal homeostasis. Altered PCs function is associated with diverse intestinal pathologies, including ileal Crohn’s disease (CD). CD patients with ileal involvement have been previously demonstrated to display impairment in PCs and decreased levels of anti-microbial peptides. Although the immunosuppressive drug Azathioprine (AZA) is widely used in CD therapy, the impact of AZA on IEC differentiation remains largely elusive. In the present study, we hypothesized that the orally administered drug AZA also exerts its effect through modulation of the intestinal epithelium and specifically via modulation of PC function. AZA-treated CD patients exhibited an ileal upregulation of AMPs on both mRNA and protein levels compared to non-AZA treated patients. Upon in vitro AZA stimulation, intestinal epithelial cell line MODE-K exhibited heightened expression levels of PC marker in concert with diminished cell proliferation but boosted mitochondrial OXPHOS activity. Moreover, differentiation of IECs, including PCs differentiation, was boosted in AZA-treated murine small intestinal organoids and was associated with decreased D-glucose consumption and decreased growth rates. Of note, AZA treatment strongly decreased Lgr5 mRNA expression as well as Ki67 positive cells. Further, AZA restored dysregulated PCs associated with mitochondrial dysfunction. AZA-dependent inhibition of IEC proliferation is accompanied by boosted mitochondria function and IEC differentiation into PC.
Functional connectivity changes in meditators and novices during yoga nidra practice
Authors: Fialoke Suruchi , Tripathi Vaibhav , Thakral Sonika , Dhawan Anju , Majahan Vidur , Garg Rahul
Published: June 2024

Yoga nidra (YN) practice aims to induce a deeply relaxed state akin to sleep while maintaining heightened awareness. Despite the growing interest in its clinical applications, a comprehensive understanding of the underlying neural correlates of the practice of YN remains largely unexplored. In this fMRI investigation, we aim to discover the differences between wakeful resting states and states attained during YN practice. The study included individuals experienced in meditation and/or yogic practices, referred to as ‘meditators’ (n = 30), and novice controls (n = 31). The GLM analysis, based on audio instructions, demonstrated activation related to auditory cues without concurrent default mode network (DMN) deactivation. DMN seed based functional connectivity (FC) analysis revealed significant reductions in connectivity among meditators during YN as compared to controls. We did not find differences between the two groups during the pre and post resting state scans. Moreover, when DMN-FC was compared between the YN state and resting state, meditators showed distinct decoupling, whereas controls showed increased DMN-FC. Finally, participants exhibit a remarkable correlation between reduced DMN connectivity during YN and self-reported hours of cumulative meditation and yoga practice. Together, these results suggest a unique neural modulation of the DMN in meditators during YN which results in being restful yet aware, aligned with their subjective experience of the practice. The study deepens our understanding of the neural mechanisms of YN, revealing distinct DMN connectivity decoupling in meditators and its relationship with meditation and yoga experience. These findings have interdisciplinary implications for neuroscience, psychology, and yogic disciplines.
Calf deep veins are safe and feasible accesses for the endovascular treatment of acute lower extremity deep vein thrombosis
Authors: Zeng Xiande , Min Xixi , Chen Wei , Zeng Xiong , Ju Zhinan , Dai Kanghui , Zhou Weimin , Qiu Jiehua
Published: June 2024

This study was designed to assess the optimal access route for the endovascular treatment of acute lower extremity deep vein thrombosis. This was a retrospective analysis of patients with acute lower extremity deep venous thrombosis who underwent endovascular treatment from February 2009 to December 2020. Patients underwent non-direct calf deep vein puncture (NDCDVP) from February 2009 to December 2011 and direct calf deep vein puncture (DCDVP) from January 2012 to December 2020. Catheter directed thrombolysis (CDT) was used to treat all patients in the NDCDVP group, whereas patients in the DCDVP group were treated with CDT or the AngioJet rhyolitic thrombectomy system. In patients exhibiting iliac vein compression syndrome, the iliac vein was dilated and implanted with a stent. Technical success rates and perioperative complication rates were compared between these two treatment groups. The NDCDVP group included 83 patients (40 males, 43 females) with a mean age of 55 ± 16 years, while the DCDVP group included 487 patients (231 males. 256 females) with a mean age of 56 ± 15 years. No significant differences were observed between these groups with respect to any analyzed clinical characteristics. The technical success rates in the NDCDVP and DCDVP groups were 96.4 and 98.2%, respectively (P > 0.05). In the NDCDVP group, the small saphenous vein (SSV)or great saphenous vein (GSV)were the most common access routes (77.1%, 64/83), whereas the anterior tibial vein (ATV) was the most common access route in the DCDVP group (78.0%, 380/487), followed by the posterior tibial vein (PTV) and peroneal vein (PV)(15.6% and 6.4%, respectively). Relative to the NDCDVP group, more patients in the DCDVP group underwent the removal of deep vein clots below the knee (7.2% [6/83] vs. 24.2% [118/487], P < 0.001). Moreover, relative to the NDCDVP group, significantly lower complication rates were evident in the DCDVP group (local infection: 10.8% vs. 0.4%, P < 0.001; local hematoma: 15.7% vs. 1.0%, P < 0.001). The position change rate was also significantly lower in the DCDVP group relative to the NDCDVP group (0% [0/487] vs. 60.2% [50/83], P < 0.001). The calf deep veins (CDVs) represent a feasible and safe access route for the endovascular treatment of lower extremity deep vein thrombosis.
Match running performance preceding scoring and conceding a goal in men’s professional soccer
Authors: Konefał Marek , Szmigiel Błażej , Bochenek Bogdan , Morgans Ryland , Żmijewski Piotr
Published: June 2024

This study aimed to investigate the potential differences in the match running performance of professional soccer players 5 min. before scoring and conceding a goal in the Polish Ekstraklasa. The sample consisted of 278 matches with 570 goals scored during official matches of the 2022/23 Polish Ekstraklasa season. All data was collected utilising the computerised multiple-camera optical tracking system TRACAB. Total distance covered (TD), standing distance (StD; < 0.72 km h−1), walking distance (WD; 0.73–7.2 km h−1), jogging distance (JG; 7.21–14.4 km h−1), running distance (RD; 14.41–19.8 km h−1), high-speed running distance (HSR; 19.81–25.2 km h−1) and sprinting distance (SprD; > 25.2 km h−1) were analysed in 5-min intervals prior to a goal scored for both teams. The employed linear mixed models showed that all examined match-running performance metrics were higher in teams that scored a goal compared to teams that conceded a goal. Within 5 min before scoring a goal in Polish Ekstraklasa matches, the scoring team produced significantly greater TD (∆ 95%CI 256.8–300.4 m; p = 0.001), WD (∆ 95%CI 52.3–95.8 m; p = 0.001), JG (∆ 95%CI 100.5–144.1 m; p = 0.001) and RD (∆ 95%CI 16.2–59.8 m; p = 0.001) compared to the conceding team, although no differences were found for HSR and SprD. These results demonstrate the enhanced identification potential of key physical performance factors influencing goal scoring in the Polish Ekstraklasa, thereby optimising the training process and improving overall performance. To enhance the effectiveness of soccer training, coaching and performance staff should consider this study's findings, that indicate an increase in the volume of medium- and low-intensity running efforts preceding a goal.
Novel peptide inhibitor of human tumor necrosis factor-α has antiarthritic activity
Authors: Sahu Debasis , Gupta Charu , Yennamalli Ragothaman M. , Sharma Shikha , Roy Saugata , Hasan Sadaf , Gupta Pawan , Sharma Vishnu Kumar , Kashyap Sujit , Kumar Santosh , Dwivedi Ved Prakash , Zhao Xiangli , Panda Amulya Kumar , Das Hasi Rani , Liu Chuan-Ju
Published: June 2024

The inhibition of tumor necrosis factor (TNF)-α trimer formation renders it inactive for binding to its receptors, thus mitigating the vicious cycle of inflammation. We designed a peptide (PIYLGGVFQ) that simulates a sequence strand of human TNFα monomer using a series of in silico methods, such as active site finding (Acsite), protein–protein interaction (PPI), docking studies (GOLD and Flex-X) followed by molecular dynamics (MD) simulation studies. The MD studies confirmed the intermolecular interaction of the peptide with the TNFα. Fluorescence-activated cell sorting and fluorescence microscopy revealed that the peptide effectively inhibited the binding of TNF to the cell surface receptors. The cell culture assays showed that the peptide significantly inhibited the TNFα-mediated cell death. In addition, the nuclear translocation of the nuclear factor kappa B (NFκB) was significantly suppressed in the peptide-treated A549 cells, as observed in immunofluorescence and gel mobility-shift assays. Furthermore, the peptide protected against joint damage in the collagen-induced arthritis (CIA) mouse model, as revealed in the micro focal-CT scans. In conclusion, this TNFα antagonist would be helpful for the prevention and repair of inflammatory bone destruction and subsequent loss in the mouse model of CIA as well as human rheumatoid arthritis (RA) patients. This calls upon further clinical investigation to utilize its potential effect as an antiarthritic drug.
Radiomic white matter parameters of functional integrity of the corticospinal tract in high-grade glioma
Authors: Wende Tim , Güresir Erdem , Wach Johannes , Vychopen Martin , Hoffmann Anastasia , Prasse Gordian , Wilhelmy Florian , Kasper Johannes
Published: June 2024

Tractography has become a widely available tool for the planning of neurosurgical operations as well as for neuroscientific research. The absence of patient interaction makes it easily applicable. However, it leaves uncertainty about the functional relevance of the identified bundles. We retrospectively analyzed the correlation of white matter markers with their clinical function in 24 right-handed patients who underwent first surgery for high-grade glioma. Morphological affection of the corticospinal tract (CST) and grade of paresis were assessed before surgery. Tractography was performed manually with MRTrix3 and automatically with TractSeg. Median and mean fractional anisotropy (FA) from manual tractography showed a significant correlation with CST affection (p = 0.008) and paresis (p = 0.015, p = 0.026). CST affection correlated further most with energy, and surface-volume ratio (p = 0.014) from radiomic analysis. Paresis correlated most with maximum 2D column diameter (p = 0.005), minor axis length (p = 0.006), and kurtosis (p = 0.008) from radiomic analysis. Streamline count yielded no significant correlations. In conclusion, mean or median FA can be used for the assessment of CST integrity in high-grade glioma. Also, several radiomic parameters are suited to describe tract integrity and may be used to quantitatively analyze white matter in the future.
Clinical management, pathogen spectrum and outcomes in patients with pyogenic liver abscess in a German tertiary-care hospital
Authors: Wendt Sebastian , Bačák Miroslav , Petroff David , Lippmann Norman , Blank Valentin , Seehofer Daniel , Zimmermann Lisa , Lübbert Christoph , Karlas Thomas
Published: June 2024

Pyogenic liver abscesses (PLA) are life-threatening disorders and require immediate treatment, but structured evidence is sparse and treatment guidelines are not established. In a retrospective observational study of 221 adult PLA patients (mean age 63 years, 63% men) treated between 2013 and 2019 at the Leipzig University Medical Center, we characterized pathogen spectrum, clinical management and outcomes. Biliary malignancies (33%), cholelithiasis (23%) and ischemic biliary tract disease (16%) were most common causes of PLA. Comorbidities included malignancies (40%) and diabetes mellitus (35%). Abdominal ultrasound was the preferred initial imaging modality (58%). Enterobacterales (58%), enterococci (42%) and streptococci (18%) were identified as most frequent pathogens. 97% of patients were treated with antibiotics and 75% of patients underwent an invasive treatment procedure. The 30-day mortality was almost identical in patients with and without underlying malignancy (14.6% vs. 14.4%, p = 0.96), while the one-year outcome differed significantly (58.4% vs. 29.6%, p < 0.001). Positive blood cultures (OR 4.78, 95% CI 1.39 to 22.5, p = 0.023) and detection of Enterobacterales (OR 3.55, 95% CI 1.40 to 9.97, p = 0.010) were associated with increased 30-day-mortality. We conclude that ultrasound, extensive microbiologic diagnosis, adequate anti-infective therapy and early intervention are crucial for the management of PLA.
Structured early childhood education exposure and childhood cognition – Evidence from an Indian birth cohort
Authors: Koshy Beena , Srinivasan Manikandan , Srinivasaraghavan Rangan , Roshan Reeba , Mohan Venkata Raghava , Ramanujam Karthikeyan , John Sushil , Kang Gagandeep
Published: June 2024

Experiences in early childhood form the bedrock of future human potential. In impoverished settings, structured early childhood education (ECE) in preschool years can augment overall childhood and later human abilities. The current study evaluates preschool learning exposure and childhood cognition, using longitudinal follow-up of a community-based birth cohort in Vellore, south India. The birth cohort study site in Vellore recruited 251 newborns between 2010 and 2012 from dense urban settlements and further followed up into childhood. Preschool enrolment details were obtained from parents. Childhood cognition was assessed by Weschler’s preschool primary scale of intelligence (WPPSI) and Malin’s intelligence scale for Indian Children (MISIC) at 5 and 9 years of age respectively. Bivariate and multivariate regression analyses were performed with adjustments for socio-economic status (SES), maternal education, stunting status and home environment. Out of 251 new-borns recruited into the MAL-ED birth cohort, 212 (84.46%) and 205 (81.7%) children were available for the 5 year and 9 year follow-up respectively. At 5 years, structured ECE of 18 to 24 months duration was significantly associated with higher cognition scores, with the highest increase in processing speed [β: 19.55 (11.26–27.77)], followed by full-scale intelligence [β: 6.75 (2.96–10.550)], even after adjustments for SES, maternal cognition, home factors and early childhood stunting status. Similarly adjusted analysis at 9 years showed that children who attended 1.5–2 years of structured ECE persisted to have higher cognition, especially in the performance domain [β: 8.82 (2.60–15.03)], followed by the full-scale intelligence [β: 7.24 (2.52–11.90)]. Follow-up of an Indian birth cohort showed that structured ECE exposure was associated with better school entry cognition as well as mid-childhood cognition. Strengthening ECE through a multi-pronged approach could facilitate to maximize cognitive potential of human capital.
Dysbiosis not observed in Canadian horses with free fecal liquid (FFL) using 16S rRNA sequencing
Authors: Wester Robert J. , Baillie Lyndsey L. , McCarthy Garrett C. , Keever Carson C. , Jeffery Lauren E. , Adams Paul J.
Published: June 2024

Free Fecal Liquid (FFL), also termed Fecal Water Syndrome (FWS), is an ailment in horses characterized by variable solid and liquid (water) phases at defecation. The liquid phase can be excreted before, during, or after the solid defecation phase. While the underlying causes of FFL are unknown, hindgut dysbiosis is suggested to be associated with FFL. Three European studies investigated dysbiosis in horses with FFL using 16S rRNA sequencing and reported results that conflicted between each other. In the present study, we also used 16S rRNA sequencing to study the fecal microbial composition in 14 Canadian horses with FFL, and 11 healthy stable mate controls. We found no significant difference in fecal microbial composition between FFL and healthy horses, which further supports that dysbiosis is not associated with FFL.
Aqueductal CSF stroke volume is associated with the burden of perivascular space enlargement in chronic adult hydrocephalus
Authors: Gallina Pasquale , Porfirio Berardino , Caini Saverio , Lolli Francesco , Scollato Antonio
Published: June 2024

The inflow of CSF into perivascular spaces (PVS) in the brain is crucial for clearing waste molecules. Inefficiency in PVS flow leads to neurodegeneration. Failure of PVS flushing is associated with CSF flow impairment in the intracranial hydrodynamic condition of CSF hypo-pulsatility. However, enlarged PVS (ePVS), a finding indicative of PVS flow dysfunction, is also present in patients with derangement of CSF dynamics characterized by CSF hyper-pulsatility, which increases CSF flow. Intriguingly, two opposite intracranial hydrodynamic conditions would lead to the same result of impairing the PVS flushing. To investigate this issue, we assessed the subsistence of a dysfunctional interplay between CSF and PVS flows and, if the case, the mechanisms preventing a hyper-pulsatile brain from providing an effective PVS flushing. We analyzed the association between phase contrast MRI aqueductal CSF stroke volume (aqSV), a proxy of CSF pulsatility, and the burden of ePVS in chronic adult hydrocephalus, a disease involving a broad spectrum of intracranial hydrodynamics disturbances. In the 147 (85 males, 62 females) patients, the age at diagnosis ranged between 28 and 88 years (median 73 years). Ninety-seven patients had tri-ventriculomegaly and 50 tetra-ventriculomegaly. According to the extent of ePVS, 113 patients had a high ePVS burden, while 34 had a low ePVS burden. aqSV, which ranged between 0 and 562 μL (median 86 μL), was increased with respect to healthy subjects. Patients presenting with less ePVS burden had higher aqSV (p < 0.002, corrected for the multiple comparisons) than those with higher ePVS burden. The present study confirmed the association between CSF dynamics and PVS flow disturbances and demonstrated this association in intracranial hyper-pulsatility. Further studies should investigate the association between PVS flow failure and CSF hypo- and hyper-pulsatility as responsible/co-responsible for glymphatic failure in other neurodegenerative diseases, particularly in diseases in which CSF disturbances can be corrected, as in chronic adult hydrocephalus.
Effect of locomotor preference on the evolution of mitochondrial genes in Bovidae
Authors: Shi Lupeng , Wang Xibao , Yang Xiufeng , Lyu Tianshu , Wang Lidong , Zhou Shengyang , Dong Yuehuan , Wu Xiaoyang , Shang Yongquan , Zhang Honghai
Published: June 2024

Locomotor preferences and habitat types may drive animal evolution. In this study, we speculated that locomotor preference and habitat type may have diverse influences on Bovidae mitochondrial genes. We used selection pressure and statistical analysis to explore the evolution of mitochondrial DNA (mtDNA) protein-coding genes (PCGs) from diverse locomotor preferences and habitat types. Our study demonstrates that locomotor preference (energy demand) drives the evolution of Bovidae in mtDNA PCGs. The habitat types had no significant effect on the rate of evolution in Bovidae mitochondrial genes. Our study provides deep insight into the adaptation of Bovidae.
Targeting the DYRK1A kinase prevents cancer progression and metastasis and promotes cancer cells response to G1/S targeting chemotherapy drugs
Authors: Laham Amina Jamal , El-Awady Raafat , Saber-Ayad Maha , Wang Ni , Yan Gang , Boudreault Julien , Ali Suhad , Lebrun Jean-Jacques
Published: June 2024

Metastatic cancer remains incurable as patients eventually loose sensitivity to targeted therapies and chemotherapies, further leading to poor clinical outcome. Thus, there is a clear medical gap and urgent need to develop efficient and improved targeted therapies for cancer patients. In this study, we investigated the role of DYRK1A kinase in regulating cancer progression and evaluated the therapeutic potential of DYRK1A inhibition in invasive solid tumors, including colon and triple-negative breast cancers. We uncovered new roles played by the DYRK1A kinase. We found that blocking DYRK1A gene expression or pharmacological inhibition of its kinase activity via harmine efficiently blocked primary tumor formation and the metastatic tumor spread in preclinical models of breast and colon cancers. Further assessing the underlying molecular mechanisms, we found that DYRK1A inhibition resulted in increased expression of the G1/S cell cycle regulators while decreasing expression of the G2/M regulators. Combined, these effects release cancer cells from quiescence, leading to their accumulation in G1/S and further delaying/preventing their progression toward G2/M, ultimately leading to growth arrest and tumor growth inhibition. Furthermore, we show that accumulation of cancer cells in G1/S upon DYRK1A inhibition led to significant potentiation of G1/S targeting chemotherapy drug responses in vitro and in vivo. This study underscores the potential for developing novel DYRK1A-targeting therapies in colon and breast cancers and, at the same time, further defines DYRK1A pharmacological inhibition as a viable and powerful combinatorial treatment approach for improving G1/S targeting chemotherapy drugs treatments in solid tumors.
Deployment and validation of the CLL treatment infection model adjoined to an EHR system
Authors: Agius Rudi , Riis-Jensen Anders C. , Wimmer Bettina , da Cunha-Bang Caspar , Murray Daniel Dawson , Poulsen Christian Bjorn , Bertelsen Marianne B. , Schwartz Berit , Lundgren Jens Dilling , Langberg Henning , Niemann Carsten Utoft
Published: June 2024

Research algorithms are seldom externally validated or integrated into clinical practice, leaving unknown challenges in deployment. In such efforts, one needs to address challenges related to data harmonization, the performance of an algorithm in unforeseen missingness, automation and monitoring of predictions, and legal frameworks. We here describe the deployment of a high-dimensional data-driven decision support model into an EHR and derive practical guidelines informed by this deployment that includes the necessary processes, stakeholders and design requirements for a successful deployment. For this, we describe our deployment of the chronic lymphocytic leukemia (CLL) treatment infection model (CLL-TIM) as a stand-alone platform adjoined to an EPIC-based Danish Electronic Health Record (EHR), with the presentation of personalized predictions in a clinical context. CLL-TIM is an 84-variable data-driven prognostic model utilizing 7-year medical patient records and predicts the 2-year risk composite outcome of infection and/or treatment post-CLL diagnosis. As an independent validation cohort for this deployment, we used a retrospective population-based cohort of patients diagnosed with CLL from 2018 onwards (n = 1480). Unexpectedly high levels of missingness for key CLL-TIM variables were exhibited upon deployment. High dimensionality, with the handling of missingness, and predictive confidence were critical design elements that enabled trustworthy predictions and thus serves as a priority for prognostic models seeking deployment in new EHRs. Our setup for deployment, including automation and monitoring into EHR that meets Medical Device Regulations, may be used as step-by-step guidelines for others aiming at designing and deploying research algorithms into clinical practice.
Apoptosis signal-regulating kinase 1 promotes inflammation in senescence and aging
Authors: Odawara Takeru , Yamauchi Shota , Ichijo Hidenori
Published: June 2024

Cellular senescence is a stress-induced, permanent cell cycle arrest involved in tumor suppression and aging. Senescent cells secrete bioactive molecules such as pro-inflammatory cytokines and chemokines. This senescence-associated secretory phenotype (SASP) has been implicated in immune-mediated elimination of senescent cells and age-associated chronic inflammation. However, the mechanisms regulating the SASP are incompletely understood. Here, we show that the stress-responsive kinase apoptosis signal-regulating kinase 1 (ASK1) promotes inflammation in senescence and aging. ASK1 is activated during senescence and increases the expression of pro-inflammatory cytokines and chemokines by activating p38, a kinase critical for the SASP. ASK1-deficient mice show impaired elimination of oncogene-induced senescent cells and an increased rate of tumorigenesis. Furthermore, ASK1 deficiency prevents age-associated p38 activation and inflammation and attenuates glomerulosclerosis. Our results suggest that ASK1 is a driver of the SASP and age-associated chronic inflammation and represents a potential therapeutic target for age-related diseases.
Light painting photography makes particulate matter air pollution visible
Authors: Pope Francis D. , Price Robin , Woolley Katherine E. , Luiu Carlo , Alam Mohammed S. , Avis William R. , Bartington Suzanne E. , Debebe Dawit , Getaneh Zerihun , Greenfield Sheila M. , Howells Rachel , Khare Mukesh , Weldetinsae Abel , Lawson Chloe , Mishra Sumit K. , Neal Ben , Newman Karen , Singh Ajit , Teklu Wodajo Bikila , Thomas G. Neil , Wilder Faye
Published: June 2024

The World Health Organization estimates that air pollution causes approximately seven million premature deaths worldwide each year. Solutions to air pollution are well known, yet this rarely equates to easily actionable. Here we demonstrate how art science collaboration can successfully highlight the issue of air pollution and create wider civic discourse around its amelioration. We document a light painting photographic technique that uses data from calibrated low-cost particulate matter sensors to measure and depict air pollution. We also use a postcard technique to grasp individuals’ sentiments regarding air pollution. The photographs from three countries, Ethiopia, India and United Kingdom, visually highlight the importance of location and occupation upon human exposure. The photographs are used as a proxy to communicate and create dialogues, spaces and places about air pollution. The sentiment analysis shows how this approach can foster awareness and create agency for stakeholders to take actions to tackle air pollution.
Machine learning and hydrodynamic proxies for enhanced rapid tsunami vulnerability assessment
Authors: Scorzini Anna Rita , Di Bacco Mario , Sugawara Daisuke , Suppasri Anawat
Published: June 2024

Coastal communities in various regions of the world are exposed to risk from tsunami inundation, requiring reliable modeling tools for implementing effective disaster preparedness and management strategies. This study advocates for comprehensive multi-variable models and emphasizes the limitations of traditional univariate fragility functions by leveraging a large, detailed dataset of ex-post damage surveys for the 2011 Great East Japan tsunami, hydrodynamic modeling of the event, and advanced machine learning techniques. It investigates the complex interplay of factors influencing building vulnerability to tsunami, with a specific focus on the hydrodynamic effects associated to tsunami propagation on land. Novel synthetic variables representing shielding and debris impact mechanisms prove to be suitable proxies for water velocity, offering a practical solution for rapid damage assessments, especially in post-event scenarios or large-scale analyses. Machine learning then emerges as a promising approach to tackle the complexities of vulnerability assessment, while providing valuable and interpretable insights.
Deficiency of CAMSAP2 impairs olfaction and the morphogenesis of mitral cells
Authors: Zhou Zhengrong , Yang Xiaojuan , Mao Aihua , Xu Honglin , Lin Chunnuan , Yang Mengge , Hu Weichang , Shao Jinhui , Xu Peipei , Li Yuejia , Li Wenguang , Lin Ruifan , Zhang Rui , Xie Qi , Xu Zhiheng , Meng Wenxiang
Published: June 2024

In developing olfactory bulb (OB), mitral cells (MCs) remodel their dendrites to establish the precise olfactory circuit, and these circuits are critical for individuals to sense odors and elicit behaviors for survival. However, how microtubules (MTs) participate in the process of dendritic remodeling remains elusive. Here, we reveal that calmodulin-regulated spectrin-associated proteins (CAMSAPs), a family of proteins that bind to the minus-end of the noncentrosomal MTs, play a crucial part in the development of MC dendrites. We observed that Camsap2 knockout (KO) males are infertile while the reproductive tract is normal. Further study showed that the infertility was due to the severe defects of mating behavior in male mice. Besides, mice with loss-of-function displayed defects in the sense of smell. Furthermore, we found that the deficiency of CAMSAP2 impairs the classical morphology of MCs, and the CAMSAP2-dependent dendritic remodeling process is responsible for this defect. Thus, our findings demonstrate that CAMSAP2 plays a vital role in regulating the development of MCs.
Modelling kinetic isotope effects for Swern oxidation using DFT-based transition state theory
Authors: Braddock D. Christopher , Lee Siwoo , Rzepa Henry S.
Published: June 2024

Kinetic isotope effects (KIEs) computed using DFT theory for the intramolecular hydrogen transfer step of the Swern oxidation compare well with experiment if basis sets of triple- or quadruple-ζ rather than double-ζ quality are used.
Click synthesis of novel 6-((1H-1,2,3-triazol-4-yl)methyl)-6H-indolo[2,3-b]quinoxalines for in vitro anticancer evaluation and docking studies
Authors: El Malah Tamer , El-Rashedy Ahmed A. , Hegab Mohamed Ibrahim , Awad Hanem M. , Shamroukh Ahmed Hussien
Published: June 2024

Anticancer activity, a novel series of 6-((1H-1,2,3-triazol-4-yl)methyl)-6H-indolo[2,3-b]quinoxalines (22–29) were designed and synthesized via the copper(i)-catalyzed azide–alkyne cycloaddition (CuAAC) reactions.
Role of NLRP3 inflammasome in nanoparticle adjuvant-mediated immune response
Authors: Ahmed Momitul , Kurungottu Pavithra , Swetha K. , Atla Sandeep , Ashok Nivethitha , Nagamalleswari Easa , Bonam Srinivasa Reddy , Sahu Bidya Dhar , Kurapati Rajendra
Published: June 2024

The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome is pivotal in orchestrating the immune response induced by most of the nanoparticle adjuvants.
Thermal reflux to synthesise C3N4 nanostructures with high yield and enhanced photocatalytic activity in hydrogen evolution
Authors: He Yihang , Wu Mingliang , Hong Kunquan
Published: June 2024

A thermal reflux method was used to synthesize g-C3N4 nanostructures with a high yield and enhanced photocatalytic activity for H2 production.
Regiodivergent C–H alkynylation of 2-arylthiazoles switched by RuII and PdII catalysis
Authors: Zhou Pengfei , Liang Xinyao , Xu Zekun , Chen Honggu , Wei Zongwu , Liang Taoyuan , Jiang Jun , Zhang Zhuan
Published: June 2024

Two complementary regiodivergent C–H alkynylations of 2-arylthiazoles are reported.
Enhancing the detonation performance of azobistriazole energetic derivatives via inducing N-oxide groups
Authors: Li Nan , Yang Xinbo , Li Xiuyuan , Peng Zihuan , Yin Zehong , Jiang Chongwen , Huang Zhihong , Li Yuchuan
Published: June 2024

The N-oxide strategy plays a crucial role in regulating the performance and safety of energetic materials.
Monitoring the state of charge of vanadium redox flow batteries with an EPR-on-a-Chip dipstick sensor
Authors: Künstner Silvio , McPeak Joseph E. , Chu Anh , Kern Michal , Dinse Klaus-Peter , Naydenov Boris , Fischer Peter , Anders Jens , Lips Klaus
Published: June 2024

The EPRoC dipstick enables the monitoring of the state of charge in corrosive electrolyte-containing solutions of vanadium redox flow batteries.
Probing microhydration-induced effects on carbonyl compounds
Authors: Aroule Olivier , Jarraya Mahmoud , Zins Emilie-Laure , Hochlaf Majdi
Published: June 2024

Characterizing the microhydration of organic molecules is a crucial step in understanding many phenomena relevant to atmospheric, biological, and industrial applications.
Phase transition and electrochemical properties of S-functionalized MXene anodes for Li-ion batteries: a first-principles investigation
Authors: Han Kun , Ji Yuhuan , Hu Qianku , Wu Qinghua , Li Dandan , Zhou Aiguo
Published: June 2024

Structural phase transition behavior of S-functionalized MXene during lithium storage can improve the lithium storage properties.
Colorimetric sensing for translational applications: from colorants to mechanisms
Authors: Jin Zhicheng , Yim Wonjun , Retout Maurice , Housel Emily , Zhong Wenbin , Zhou Jiajing , Strano Michael S. , Jokerst Jesse V.
Published: June 2024

This review summarizes insights into colorant selection and signal mechanisms for the development of colorimetric sensing and POC sensors.
Materials science in the era of large language models: a perspective
Authors: Lei Ge , Docherty Ronan , Cooper Samuel J.
Published: June 2024

This perspective paper explores the potential of Large Language Models (LLMs) in materials science, highlighting their abilities to handle ambiguous tasks, automate processes, and extract knowledge at scale across various disciplines.
Non-stoichiometry and electrochemical properties of lithiated iron hydroxysulfides
Authors: Mir C. , Giaume D. , Morcrette M. , Sougrati M. T. , Wallez G. , Courty M. , Chakir M. , Barboux P.
Published: June 2024

We studied the electrochemical lithium intercalation in LiOHFeS. After a first irreversible reaction the resulting new material reversibly cycles one lithium atom involving the Fe3+/Fe2+ redox couple: Li2FeOS ↔ Li+ + e− + LiFeOS.
C–H bond activation at antimony(iii): synthesis and reactivity of Sb(iii)–oxyaryl species
Authors: Duneş Gabriel , Cordier Marie , Kahlal Samia , Pöllnitz Alpar , Saillard Jean-Yves , Silvestru Cristian , Sarazin Yann
Published: June 2024

The antimony(iii)-oxyaryl [{NCNMe4}Sb(C6H2-tBu2-3,5-O-4)] forms upon C–H activation, with charged species and heterolytic bond cleaving and forming steps. The reactivity of the complex, which exhibits zwitterionic and quinoidal features, was probed.
Millet flour as a potential ingredient in fish sausage for health and sustainability
Authors: Elavarasan Krishnamoorthy , Malini Mathew , Ninan George , Ravishankar C. N. , Dayakar B. R.
Published: June 2024

A sustainable food product, ‘Fish-millet sausage’, suitable for nutritional intervention programs to achieve SDG-2 was developed using 9 varieties of millet. Millet-added sausages had better textural and sensory acceptability.
Prospects of using non-thermal technologies for chia seed mucilage extraction
Authors: Solanki Divyang , Oey Indrawati , Prakash Sangeeta , Bhandari Bhesh , Sahu Jatindra K.
Published: June 2024

This review summarized the use and prospects of non-thermal technologies for extracting and modifying chia seed mucilage, which has food hydrocolloid properties.
Electrostatically responsive liquid gating system for controlled microbubble generation
Authors: Zeng Guochao , Zhang Yunmao , Fang Zhongyi , Yu Lejian , Zhang Yawen , Wang Shaojie , Hou Xu
Published: June 2024

The electrostatically responsive liquid gating system employs small electric potentials to control the adsorption and desorption of anionic surfactants, enabling intelligent regulation of bubble size during the membrane dispersion process.
Ultra-high resolution, multi-scenario, super-elastic inductive strain sensors based on liquid metal for the wireless monitoring of human movement
Authors: Mao Jian , He Zidong , Wu Yuanzhao , Cao Jinwei , Zhao Shijing , Chen Bin , Shang Jie , Liu Yiwei , Li Run-Wei
Published: June 2024

The paper presents a new liquid metal putty strain sensor that can measure strains from 0.05% to 300%. A wireless motion monitoring system is developed based on this sensor, which is expected to be used for health and motion tracking.
Effect of CO2 release behavior on the crosslinking degree of alginate hydrogels prepared with CaCO3 and carbonated water
Authors: Teshima Ryota , Osawa Shigehito , Hirose Kaoru , Kawano Yayoi , Kikuchi Akihiko , Hanawa Takehisa , Otsuka Hidenori
Published: June 2024

The CO2 release behavior, i.e., “post-gelation condition,” affects the degree of cross-linking, an essential parameter for determining hydrogel properties.
Synthesis and symmetry of perovskite oxynitride CaW(O,N)3
Authors: Sweers Matthew E. , Liu Tzu-chen , Shen Jiahong , Lu Bingzhang , Freeland John W. , Wolverton Christopher , Gonzalez Aviles Gabriela B. , Seitz Linsey C.
Published: June 2024

Perovskite oxynitrides are promising electrocatalysts and photoabsorbers; their heteroanionic structures present an interesting case study in crystal symmetry. Novel CaW(O,N)3 is analyzed with X-ray and neutron diffraction and computational models.
Pyrolysis of naphthol functionalized polytriarylamine for efficient sodium-ion storage
Authors: Kim Taehyoung , Chae Seongwook , Lee Taewoong , Yoon Young Rok , Park Jae Bin , Kim Byeong Jin , Lee Kyoungeun , Song In Young , Yun Hwanhui , Lee Wang-Eun , Heo Kyuyoung , Kim Sang Youl , Lee Jinhee , Lee Jin Hong
Published: June 2024

Pyrolysis of poly(DNap-OH) results in the formation of disordered carbon with high char-yield. The pyrolyzed Poly(DNap-OH) shows enhanced electrochemical performance in SIBs via surface-induced Na+ storage, attributed to N- and O-moieties.
Enhanced stability of boron modified NiFe hydroxide for oxygen evolution reaction
Authors: Hong Yewon , Choi Juhyung , Lee Eunchong , Hwang Yun Jeong
Published: June 2024

The introduction of boron into NiFe hydroxide enhances activity and stability for oxygen evolution reaction as it maintains a uniform distribution of Fe species on the active surface through facilitated dissolution and redeposition cycles.
Fluorescent probes for imaging: a focus on atherosclerosis
Authors: Jia Jing , Li Li , Wu Zhifang , Li Sijin
Published: June 2024

This review focusses on an overview of the research progress of fluorescence probes in the imaging of atherosclerosis.
Biopharmaceutical advancement of efonidipine hydrochloride ethanolate through amorphous solid dispersion of a Parteck SLC mesoporous silica polymer
Authors: Bharati Swati , Gaikwad Vinod , Chellampillai Bothiraja
Published: June 2024

Parteck® SLC mesoporous silica based amorphous solid dispersion improved solubility, bioavailability of efonidipine hydrochloride ethanolate.
Selective C2 and C3 phosphorylmethylation of indoles with a phosphorylmethyl dibenzothiophenium reagent
Authors: Shi Xiaomin , Qu Hongmei , Wu Yaxing , Wang Fei , Chen Chao
Published: June 2024

A novel electrophilic phosphorylmethylating reagent with excellent selectivity for the formation of indole C(sp2)–CH2PO(OEt)2 bonds at position C2 with a photoredox catalyst and at position C3 with a copper catalyst has been developed.
Microrail-assisted liposome trapping and aligning in microfluidic channels
Authors: Okada Shun , Shoji Kan
Published: June 2024

A microrail-assisted technique for constructing liposome assemblies with specific shapes in a microfluidic device.
Structural-model-based genome mining can efficiently discover novel non-canonical terpene synthases hidden in genomes of diverse species
Authors: Abe Tohru , Shiratori Haruna , Kashiwazaki Kosuke , Hiasa Kazuma , Ueda Daijiro , Taniguchi Tohru , Sato Hajime , Abe Takashi , Sato Tsutomu
Published: June 2024

Non-canonical terpene synthases with primary sequences that are unrecognizable as canonical terpene synthases could be discovered through structural-model-based genome mining.
Synthesis and electrocatalytic applications of hybrid nanomaterials containing low-dimensional metals
Authors: Wang Xixi , Jiao Xinran , Wang Yunhao , Feng Fukai , Huang Zhiqi , Ge Yiyao
Published: June 2024

In this review, recent progress in the synthesis and electrocatalytic applications of hybrid nanomaterials containing low-dimensional metals was outlined and some promising future directions were proposed.
High-efficiency photocatalytic reduction of Cr(vi) by Z-scheme electron transfer in UiO-66-NH2@HDU-25 heterojunctions
Authors: Lu Wen , Wang Chen , Song Wenhui , Zhang Zhixiong , Xie Chengde , Wang Jianjun
Published: June 2024

The heavy metal ion hexavalent chromium (Cr(vi)) in wastewater significantly threatens public health.
Magnetic anisotropy evolution with Fe content in electrodeposited Ni100−xFex thin films
Authors: Begué A. , Cotón N. , Ranchal R.
Published: June 2024

Agreement between experimental results and a theoretical model. Crystalline structure, elasticity, shape and pairs contribute to the magnetic anisotropy of Ni100−xFex alloys.