bluuebunny/crossref_metadata_2025 huggingface dataset:
Catholic Social Teaching in Practice
Authors: Yuengert Andrew M.
Published: June 2023

Although the virtues are implicit in Catholic Social Teaching, they are too often overlooked.  In this pioneering study, Andrew M. Yuengert draws on the neo-Aristotelian virtues tradition to bring the virtue of practical wisdom into an explicit and wide-ranging engagement with the Church's social doctrine.  Practical wisdom and the virtues clarify the meaning of Christian personalism, highlight the irreplaceable role of the laity in social reform, and bring attention to the important task of lay formation in virtue. This form of wisdom also offers new insights into the Church's dialogue with economics and the social sciences, and reframes practical political disagreements between popes, bishops, and the laity in a way that challenges both laypersons and episcopal leadership. Yuengert's study respects the Church's social tradition, while showing how it might develop to be more practical.  By proposing active engagement with practical wisdom, he demonstrates how Catholic Social Teaching can more effectively inform and inspire practical social reform.
Evaluating a pilot, structured, face-to-face, antimicrobial stewardship, prospective audit-and-feedback program in emergency general surgery service in a community hospital
Authors: Chan April J. , Tsang Melanie E. , Langford Bradley J. , Nisenbaum Rosane , Wan Michael , Downing Mark A.
Published: June 2023

Background:

Prospective audit and feedback (PAF) is an established practice in critical care settings but not in surgical populations. We pilot-tested a structured face-to-face PAF program for our acute-care surgery (ACS) service.

Methods:

This was a mixed-methods study. For the quantitative analysis, the structured PAF period was from August 1, 2017, to April 30, 2019. The ad hoc PAF period was from May 1, 2019, to January 31, 2021. Interrupted time-series segmented negative binomial regression analysis was used to evaluate change in antimicrobial usage measured in days of therapy per 1,000 patient days for all systemic and targeted antimicrobials. Secondary outcomes included C. difficile infections, length of stay and readmission within 30 days. Each secondary outcome was analyzed using a logistic regression or negative binomial regression model. For the qualitative analyses, all ACS surgeons and trainees from November 23, 2015, to April 30, 2019, were invited to participate in an email-based anonymous survey developed using implementation science principles. Responses were measured using counts.

Results:

In total, 776 ACS patients were included in the structured PAF period and 783 patients were included in the in ad hoc PAF period. No significant changes in level or trend for antimicrobial usage were detected for all and targeted antimicrobials. Similarly, no significant differences were detected for secondary outcomes. The survey response rate was 25% (n = 10). Moreover, 50% agreed that PAF provided them with skills to use antimicrobials more judiciously, and 80% agreed that PAF improved the quality of antimicrobial treatment for their patients.

Conclusion:

Structured PAF showed clinical outcomes similar to ad hoc PAF. Structured PAF was well received and was perceived as beneficial by surgical staff.
P.006 Alzheimer’s disease CSF biomarker testing and its impacts on clinical management: findings from the IMPACT-AD BC study
Authors: Patel KJ , Best JR , Yang D , Chambers C , Lee PE , Henri-Bhargava A , Funnell CR , Foti DJ , Feldman HH , Pettersen JA , Nygaard HB , Hsiung GR , DeMarco ML
Published: June 2023

Background: Within the IMPACT-AD BC study, we sought to address the gap in knowledge around how the use of Alzheimer’s disease (AD) CSF biomarker testing impacts clinical management. Methods: IMPACT-AD BC (NCT05002699, impactAD.org) is an observational, longitudinal study examining the role of AD CSF biomarker testing (i.e., amyloid-beta and tau proteoforms) in medical and personal decision-making, and health economics. For medical decision-making, physicians completed surveys on patient management plans before and after receiving the biomarker findings. Overall change in management was assessed as a composite measure of changes in the use of: (i) AD symptomatic medications, (ii) other dementia-relevant medications, (iii) diagnostic procedures, and (iv) referrals or counselling. Results: Of the 142 participants, 66% were determined to have CSF biomarker profiles on the AD continuum. Overall change in management was observed in 89% of patients, with the greatest changes by category being: diagnostic procedures > referrals and counselling > AD symptomatic medications > other dementia-relevant medications. Conclusions: The use of AD CSF biomarker testing increases diagnostic confidence and aids in medical decision-making. Notably, the addition of biomarker testing leads to a reduction in the use of other diagnostic procedures, helps optimize pharmacotherapy and results in increased physician-patient/family member counselling.
Morphological traits for rapid and simple separation of native and introduced common reed (Phragmites australis)
Authors: McTavish Michael J. , Smith Tyler , Mechanda Subbaiah , Smith Sandy M. , Bourchier Robert S.
Published: June 2023

Effective management of the introduced invasive grass common reed [Phragmites australis (Cav.) Trin. ex Steud.] requires the ability to differentiate between the introduced and native subspecies found in North America. While genetic tools are useful for discriminating between the subspecies, morphological identification is a useful complementary approach that is low to zero cost and does not require specialized equipment or technical expertise. The objective of our study was to identify the best morphological traits for rapid and simple identification of native and introduced P. australis. A suite of 22 morphological traits were measured in 21 introduced and 27 native P. australis populations identified by genetic barcoding across southern Ontario, Canada. Traits were compared between the subspecies to identify measurements that offered reliable, diagnostic separation. Overall, 21 of the 22 traits differed between the subspecies, with four offering complete separation: the retention of leaf sheaths on dead stems; a categorical assessment of stem color; the base height of the ligule, excluding the hairy fringe; and a combined measurement of leaf length and lower glume length. Additionally, round fungal spots on the stem occurred only on the native subspecies and never on the sampled introduced populations. The high degree of variation observed in traits within and between the subspecies cautions against a “common wisdom” approach to identification or automatic interpretation of intermediate traits as indicative of aberrant populations or hybridization. As an alternative, we have compiled the five best traits into a checklist of simple and reliable measurements to identify native and introduced P. australis. This guide will be most applicable for samples collected in the late summer and fall in the Great Lakes region but can also inform best practices for morphological identification in other regions as well.
Barrier Lyapunov function and adaptive backstepping-based control of a quadrotor UAV
Authors: Khadhraoui Adel , Zouaoui Amir , Saad Mohamad
Published: June 2023

This paper presents backstepping control and backstepping constraint control approaches for a quadrotor unmanned aerial vehicle (UAV) control system. The proposed methods are applied to a Parrot Mambo drone model to control rotational motion along the
$x$
,
$y$
, and
$z$
axes during hovering and trajectory tracking. In the backstepping control approach, each state of the system controls the previous state and is called “virtual control.” The last state is controlled by the real control input. The idea is to compute, in several steps, a control law that ensures the asymptotic stability of the system. The backstepping constraint control method, based on barrier Lyapunov functions (BLFs), is designed not only to track the desired trajectory but also to guarantee no violation of the position and angle constraints. Symmetric BLFs are introduced in the design of the controller. A nonlinear mathematical model is considered in this study. Based on Lyapunov stability theory, it can be concluded that the proposed controllers can guarantee the stability of the UAV system and the state converges asymptotically to the desired trajectory. To make the control robust, an adaptation law is applied to the backstepping control that estimates the unknown parameters and ensures their convergence to their respective values. Validation of the proposed controllers was performed by simulation on a flying UAV system.
Associations of students’ linguistic distance to the language of instruction and classroom composition with English reading and listening skills
Authors: Jaekel Nils , Ritter Markus , Jaekel Julia
Published: June 2023

Globally classrooms are increasingly linguistically diverse. Research often oversimplifies lived linguistic heterogeneity as binary variables: native versus non-native. Linguistic distance (LD) measures allow a fine-grained operationalization of linguistic diversity in foreign language education. This study investigated associations of cognate LDs of students’ home languages and classroom heterogeneity with English as a Foreign Language skills. Data were collected from a diverse sample of 5,130 Year 5 students in Germany. Mixed-effects linear models confirmed our hypotheses that higher individual LDs and a higher proportion of multilingual learners per classroom were both independently associated with lower English proficiency. Multilingual learners with higher cognate LDs to English and students in more linguistically heterogeneous classrooms had lower English proficiency. The results emphasize the need to assess LD in research to better differentiate between students. Foreign language classrooms seem not to address linguistic diversity adequately and need to readjust their focus to better meet multilingual learners’ needs.
Constraining Water Depth Influence on Organic Paleotemperature Proxies Using Sedimentary Archives
Authors: Varma Devika , Hättig Katrin , van der Meer Marcel T. J. , Reichart Gert‐Jan , Schouten Stefan
Published: June 2023

The TEX86 paleothermometer has been extensively used to reconstruct past sea water temperatures, but it remains unclear which export depths the proxy represents. Here we used a novel approach to better constrain the proxy recording depths by investigating paleotemperature proxies (TEX86, , RI−OH and RI−OH′) from two pairs of proximal (<12 km apart) cores from Chilean and Angola margins, respectively. These cores are from steep continental slopes and lower shelves, which leads to a substantial difference in water depth between them despite being closely located. Surprisingly, the deep and the shallow records at the Chilean margin show dissimilarities, in contrast to the similar records from the Angola margin, which may be due to post‐depositional alteration at the former sites. In contrast, the TEX86 records were statistically indistinguishable between the sites at both the locations, even though the GDGT [2]/[3] ratio suggests GDGTs derived from potentially different archaeal communities residing at different depths. A short‐lived difference between the TEX86 records is observed during the last glacial period at the Angola margin, possibly due to a contribution of Antarctic Intermediate Waters to the deep site. Modelling suggests that the TEX86 source signal at our core sites reaches its peak abundance at water depths shallower than 350 m. The RI−OH and RI−OH′ records show similar variability as the TEX86 records, although regional differences in their absolute temperature estimates exist. Our approach using proximal sediment cores at steep slopes appears useful to constrain the export depth of organic proxy signals for paleo‐reconstructions.
Inhibition of dorsal raphe GABAergic neurons blocks hyperalgesia during heroin withdrawal
Authors: Alvarez-Bagnarol Yocasta , García Raul , Vendruscolo Leandro F. , Morales Marisela
Published: June 2023

Opioid withdrawal signs, such as hyperalgesia, are manifestations of opioid use disorder that may contribute to opioid seeking and taking. We have previously identified an association between dorsal raphe (DR) neurons and the expression of hyperalgesia during spontaneous heroin withdrawal. Here, we found that chemogenetic inhibition of DR neurons decreased hyperalgesia during spontaneous heroin withdrawal in male and female C57/B6 mice. By neuroanatomy, we identified three major subtypes of DR neurons expressing μ-opioid receptors (MOR) that were activated in hyperalgesia during spontaneous withdrawal, those expressing vesicular GABA transporter (VGaT), glutamate transporter 3 (VGluT3), or co-expressing VGluT3 and tryptophan hydroxylase (TPH). In contrast, we identified a small population of DR-MOR neurons expressing solely TPH, which were not activated in hyperalgesia during spontaneous withdrawal. Collectively, these findings indicate a role of the DR in hyperalgesia during spontaneous heroin withdrawal mediated, in part, by the activation of local MOR-GABAergic, MOR-glutamatergic and MOR-co-releasing glutamatergic-serotonergic neurons. We found that  specific chemogenetic inhibition of DR-VGaT neurons blocked hyperalgesia during spontaneous heroin withdrawal in male and female mice. Collectively, these findings indicate that DR-GABAergic neurons play a role in the expression of hyperalgesia during spontaneous heroin withdrawal.
Distinct bacterial population dynamics and disease dissemination after biofilm dispersal and disassembly
Authors: Ma Yeping , Deng Yanlin , Hua Haojun , Khoo Bee Luan , Chua Song Lin
Published: June 2023

Microbial communities that form surface-attached biofilms must release and disperse their constituent cells into the environment to colonize fresh sites for continued survival of their species. For pathogens, biofilm dispersal is crucial for microbial transmission from environmental reservoirs to hosts, cross-host transmission, and dissemination of infections across tissues within the host. However, research on biofilm dispersal and its consequences in colonization of fresh sites remain poorly understood. Bacterial cells can depart from biofilms via stimuli-induced dispersal or disassembly due to direct degradation of the biofilm matrix, but the complex heterogeneity of bacterial populations released from biofilms rendered their study difficult. Using a novel 3D-bacterial “biofilm-dispersal-then-recolonization” (BDR) microfluidic model, we demonstrated that Pseudomonas aeruginosa biofilms undergo distinct spatiotemporal dynamics during chemical-induced dispersal (CID) and enzymatic disassembly (EDA), with contrasting consequences in recolonization and disease dissemination. Active CID required bacteria to employ bdlA dispersal gene and flagella to depart from biofilms as single cells at consistent velocities but could not recolonize fresh surfaces. This prevented the disseminated bacteria cells from infecting lung spheroids and Caenorhabditis elegans in on-chip coculture experiments. In contrast, EDA by degradation of a major biofilm exopolysaccharide (Psl) released immotile aggregates at high initial velocities, enabling the bacteria to recolonize fresh surfaces and cause infections in the hosts efficiently. Hence, biofilm dispersal is more complex than previously thought, where bacterial populations adopting distinct behavior after biofilm departure may be the key to survival of bacterial species and dissemination of diseases.
METTL3-dependent m6A methylation facilitates uterine receptivity and female fertility via balancing estrogen and progesterone signaling
Authors: Wan Shuo , Sun Yadong , Zong Jinbao , Meng Wanqing , Yan Jiacong , Chen Kexin , Wang Sanfeng , Guo Daji , Xiao Zhiqiang , Zhou Qinghua , Yin Zhinan , Yang Meixiang
Published: June 2023

Infertility is a worldwide reproductive health problem and there are still many unknown etiologies of infertility. In recent years, increasing evidence emerged and confirmed that epigenetic regulation played a leading role in reproduction. However, the function of m6A modification in infertility remains unknown. Here we report that METTL3-dependent m6A methylation plays an essential role in female fertility via balancing the estrogen and progesterone signaling. Analysis of GEO datasets reveal a significant downregulation of METTL3 expression in the uterus of infertile women with endometriosis or recurrent implantation failure. Conditional deletion of Mettl3 in female reproductive tract by using a Pgr-Cre driver results in infertility due to compromised uterine endometrium receptivity and decidualization. m6A-seq analysis of the uterus identifies the 3’UTR of several estrogen-responsive genes with METTL3-dependent m6A modification, like Elf3 and Celsr2, whose mRNAs become more stable upon Mettl3 depletion. However, the decreased expression levels of PR and its target genes, including Myc, in the endometrium of Mettl3 cKO mice indicate a deficiency in progesterone responsiveness. In vitro, Myc overexpression could partially compensate for uterine decidualization failure caused by Mettl3 deficiency. Collectively, this study reveals the role of METTL3-dependent m6A modification in female fertility and provides insight into the pathology of infertility and pregnancy management.
A novel N6-Deoxyadenine methyltransferase METL-9 modulates C. elegans immunity via dichotomous mechanisms
Authors: Ma Chengchuan , Xue Tingling , Peng Qi , Zhang Jie , Guan Jialiang , Ding Wanqiu , Li Yi , Xia Peixue , Zhou Liankui , Zhao Tianyu , Wang Sheng , Quan Li , Li Chuan-Yun , Liu Ying
Published: June 2023

N6-Methyldeoxyadenine (6mA) has been rediscovered as a DNA modification with potential biological function in metazoans. However, the physiological function and regulatory mechanisms regarding the establishment, maintenance and removal of 6mA in eukaryotes are still poorly understood. Here we show that genomic 6mA levels change in response to pathogenic infection in Caenorhabditis elegans (C. elegans). We further identify METL-9 as the methyltransferase that catalyzes DNA 6mA modifications upon pathogen infection. Deficiency of METL-9 impairs the induction of innate immune response genes and renders the animals more susceptible to pathogen infection. Interestingly, METL-9 functions through both 6mA-dependent and -independent mechanisms to transcriptionally regulate innate immunity. Our findings reveal that 6mA is a functional DNA modification in immunomodulation in C. elegans.
Nanowire-based smart windows combining electro- and thermochromics for dynamic regulation of solar radiation
Authors: Sheng Si-Zhe , Wang Jin-Long , Zhao Bin , He Zhen , Feng Xue-Fei , Shang Qi-Guo , Chen Cheng , Pei Gang , Zhou Jun , Liu Jian-Wei , Yu Shu-Hong
Published: June 2023

Smart window is an attractive option for efficient heat management to minimize energy consumption and improve indoor living comfort owing to their optical properties of adjusting sunlight. To effectively improve the sunlight modulation and heat management capability of smart windows, here, we propose a co-assembly strategy to fabricate the electrochromic and thermochromic smart windows with tunable components and ordered structures for the dynamic regulation of solar radiation. Firstly, to enhance both illumination and cooling efficiency in electrochromic windows, the aspect ratio and mixed type of Au nanorods are tuned to selectively absorb the near-infrared wavelength range of 760 to 1360 nm. Furthermore, when assembled with electrochromic W18O49 nanowires in the colored state, the Au nanorods exhibit a synergistic effect, resulting in a 90% reduction of near-infrared light and a corresponding 5 °C cooling effect under 1-sun irradiation. Secondly, to extend the fixed response temperature value to a wider range of 30–50 °C in thermochromic windows, the doping amount and mixed type of W-VO2 nanowires are carefully regulated. Last but not the least, the ordered assembly structure of the nanowires can greatly reduce the level of haze and enhance visibility in the windows.
The curious case of the structural phase transition in SnSe insights from neutron total scattering
Authors: Jiang Bo , Neu Jennifer , Olds Daniel , Kimber Simon A. J. , Page Katharine , Siegrist Theo
Published: June 2023

At elevated temperatures SnSe is reported to undergo a structural transition from the low symmetry orthorhombic GeS-type to a higher symmetry orthorhombic TlI-type. Although increasing symmetry should likewise increase lattice thermal conductivity, many experiments on single crystals and polycrystalline materials indicate that this is not the case. Here we present temperature dependent analysis of time-of-flight (TOF) neutron total scattering data in combination with theoretical modeling to probe the local to long-range evolution of the structure. We report that while SnSe is well characterized on average within the high symmetry space group above the transition, over length scales of a few unit cells SnSe remains better characterized in the low symmetry GeS-type space group. Our finding from robust modeling provides further insight into the curious case of a dynamic order-disorder phase transition in SnSe, a model consistent with the soft-phonon picture of the high thermoelectric power above the phase transition.
Structural mapping of Nav1.7 antagonists
Authors: Wu Qiurong , Huang Jian , Fan Xiao , Wang Kan , Jin Xueqin , Huang Gaoxingyu , Li Jiaao , Pan Xiaojing , Yan Nieng
Published: June 2023

Voltage-gated sodium (Nav) channels are targeted by a number of widely used and investigational drugs for the treatment of epilepsy, arrhythmia, pain, and other disorders. Despite recent advances in structural elucidation of Nav channels, the binding mode of most Nav-targeting drugs remains unknown. Here we report high-resolution cryo-EM structures of human Nav1.7 treated with drugs and lead compounds with representative chemical backbones at resolutions of 2.6-3.2 Å. A binding site beneath the intracellular gate (site BIG) accommodates carbamazepine, bupivacaine, and lacosamide. Unexpectedly, a second molecule of lacosamide plugs into the selectivity filter from the central cavity. Fenestrations are popular sites for various state-dependent drugs. We show that vinpocetine, a synthetic derivative of a vinca alkaloid, and hardwickiic acid, a natural product with antinociceptive effect, bind to the III-IV fenestration, while vixotrigine, an analgesic candidate, penetrates the IV-I fenestration of the pore domain. Our results permit building a 3D structural map for known drug-binding sites on Nav channels summarized from the present and previous structures.
In silico screening for As/Se-free ovonic threshold switching materials
Authors: Clima Sergiu , Matsubayashi Daisuke , Ravsher Taras , Garbin Daniele , Delhougne Romain , Kar Gouri Sankar , Pourtois Geoffrey
Published: June 2023

Restricted use of hazardous environmental chemicals is one important challenge that the semiconductor industry needs to face to improve its sustainability. Ovonic threshold switching (OTS) ternary compound materials used in memory selector devices contain As and Se. Engineering these elements out of these materials requires significant research effort. To facilitate this process, we performed systematic material screening for As/Se-free ternary materials, based on ab-initio simulations. To limit the large amount of possible chemical compositions to fewer promising candidates, we used physics-based material parameter filters like material stability, electronic properties, or change in polarizability. The OTS gauge concept is introduced as a computed parameter to estimate the probability of a material to show an OTS behavior. As a result, we identified 35 As/Se-free ternary alloy compositions for stand-alone OTS memory applications, as well as 12 compositions for RRAM selector applications. This work aims seeding the development of As/Se-free OTS materials.
Janus porous polylactic acid membranes with versatile metal–phenolic interface for biomimetic periodontal bone regeneration
Authors: Zhang Yaping , Chen Yi , Ding Tian , Zhang Yandi , Yang Daiwei , Zhao Yajun , Liu Jin , Ma Baojin , Bianco Alberto , Ge Shaohua , Li Jianhua
Published: June 2023

Conventional treatment to periodontal and many other bone defects requires the use of barrier membranes to guided tissue regeneration (GTR) and guided bone regeneration (GBR). However, current barrier membranes normally lack of the ability to actively regulate the bone repairing process. Herein, we proposed a biomimetic bone tissue engineering strategy enabled by a new type of Janus porous polylactic acid membrane (PLAM), which was fabricated by combining unidirectional evaporation-induced pore formation with subsequent self-assembly of a bioactive metal–phenolic network (MPN) nanointerface. The prepared PLAM-MPN simultaneously possesses barrier function on the dense side and bone-forming function on the porous side. In vitro, the presence of MPN nanointerface potently alleviated the proinflammatory polarization of mice bone marrow-derived macrophages (BMDMs), induced angiogenesis of human umbilical vein endothelial cells (HUVECs), and enhanced the attachment, migration and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). The implantation of PLAM-MPN into rat periodontal bone defects remarkably enhanced bone regeneration. This bioactive MPN nanointerface within a Janus porous membrane possesses versatile capacities to regulate cell physiology favoring bone regeneration, demonstrating great potential as GTR and GBR membranes for clinical applications.
Prospection deficits in patients with first-episode schizophrenia: a cross-sectional comparative study
Authors: Fung Antoinette C. O. , Zhang Rui-ting , Yip Stanley S. L. , Poon Grace K. S. , Cheng Chi-Wai , Yang Tian-xiao , Lui Simon S. Y. , Chan Raymond C. K.
Published: June 2023

Prospection refers to the ability to simulate and pre-experience future events. Schizophrenia patients have difficulty in anticipating pleasure in future events, but previous studies examined prospection deficits in chronic schizophrenia patients. This study aimed to investigate prospection deficits in first-episode schizophrenia patients. Thirty first-episode schizophrenia patients and 31 healthy controls completed the Affective Prospection Task, which utilized pictorial cues to involve positive, neutral and negative prospection. Participants’ ratings regarding the phenomenal characteristics of their prospected events were collected, and their prospected narratives were coded using a valid scoring manual. We also assessed intelligence, working memory and logical memory. The results showed, in all participants, valence of the cues significantly influenced participants’ sense of pre-experience, temporal distance, emotion experience, vividness and participation of the prospected events, as well as the richness of sensory details. The two groups did not differ in self-report phenomenal characteristics of their prospected events. For coded characteristics, schizophrenia patients’ prospected narratives were less rich in thought/emotion than controls, even after controlling for intelligence and memory deficits. We extended empirical evidence for prospection deficits from chronic schizophrenia samples to first-episode schizophrenia patients.
An all-in-one nanoprinting approach for the synthesis of a nanofilm library for unclonable anti-counterfeiting applications
Authors: Zhang Junfang , Liu Yuxin , Njel Christian , Ronneberger Sebastian , Tarakina Nadezda V. , Loeffler Felix F.
Published: June 2023

In addition to causing trillion-dollar economic losses every year, counterfeiting threatens human health, social equity and national security. Current materials for anti-counterfeiting labelling typically contain toxic inorganic quantum dots and the techniques to produce unclonable patterns require tedious fabrication or complex readout methods. Here we present a nanoprinting-assisted flash synthesis approach that generates fluorescent nanofilms with physical unclonable function micropatterns in milliseconds. This all-in-one approach yields quenching-resistant carbon dots in solid films, directly from simple monosaccharides. Moreover, we establish a nanofilm library comprising 1,920 experiments, offering conditions for various optical properties and microstructures. We produce 100 individual physical unclonable function patterns exhibiting near-ideal bit uniformity (0.492 ± 0.018), high uniqueness (0.498 ± 0.021) and excellent reliability (>93%). These unclonable patterns can be quickly and independently read out by fluorescence and topography scanning, greatly improving their security. An open-source deep-learning model guarantees precise authentication, even if patterns are challenged with different resolutions or devices.
Camonsertib in DNA damage response-deficient advanced solid tumors: phase 1 trial results
Authors: Yap Timothy A. , Fontana Elisa , Lee Elizabeth K. , Spigel David R. , Højgaard Martin , Lheureux Stephanie , Mettu Niharika B. , Carneiro Benedito A. , Carter Louise , Plummer Ruth , Cote Gregory M. , Meric-Bernstam Funda , O’Connell Joseph , Schonhoft Joseph D. , Wainszelbaum Marisa , Fretland Adrian J. , Manley Peter , Xu Yi , Ulanet Danielle , Rimkunas Victoria , Zinda Mike , Koehler Maria , Silverman Ian M. , Reis-Filho Jorge S. , Rosen Ezra
Published: June 2023

Predictive biomarkers of response are essential to effectively guide targeted cancer treatment. Ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) have been shown to be synthetic lethal with loss of function (LOF) of ataxia telangiectasia-mutated (ATM) kinase, and preclinical studies have identified ATRi-sensitizing alterations in other DNA damage response (DDR) genes. Here we report the results from module 1 of an ongoing phase 1 trial of the ATRi camonsertib (RP-3500) in 120 patients with advanced solid tumors harboring LOF alterations in DDR genes, predicted by chemogenomic CRISPR screens to sensitize tumors to ATRi. Primary objectives were to determine safety and propose a recommended phase 2 dose (RP2D). Secondary objectives were to assess preliminary anti-tumor activity, to characterize camonsertib pharmacokinetics and relationship with pharmacodynamic biomarkers and to evaluate methods for detecting ATRi-sensitizing biomarkers. Camonsertib was well tolerated; anemia was the most common drug-related toxicity (32% grade 3). Preliminary RP2D was 160 mg weekly on days 1–3. Overall clinical response, clinical benefit and molecular response rates across tumor and molecular subtypes in patients who received biologically effective doses of camonsertib (>100 mg d−1) were 13% (13/99), 43% (43/99) and 43% (27/63), respectively. Clinical benefit was highest in ovarian cancer, in tumors with biallelic LOF alterations and in patients with molecular responses. ClinicalTrials.gov registration: NCT04497116.
Predicting U.S. county opioid poisoning mortality from multi-modal social media and psychological self-report data
Authors: Giorgi Salvatore , Yaden David B. , Eichstaedt Johannes C. , Ungar Lyle H. , Schwartz H. Andrew , Kwarteng Amy , Curtis Brenda
Published: June 2023

Opioid poisoning mortality is a substantial public health crisis in the United States, with opioids involved in approximately 75% of the nearly 1 million drug related deaths since 1999. Research suggests that the epidemic is driven by both over-prescribing and social and psychological determinants such as economic stability, hopelessness, and isolation. Hindering this research is a lack of measurements of these social and psychological constructs at fine-grained spatial and temporal resolutions. To address this issue, we use a multi-modal data set consisting of natural language from Twitter, psychometric self-reports of depression and well-being, and traditional area-based measures of socio-demographics and health-related risk factors. Unlike previous work using social media data, we do not rely on opioid or substance related keywords to track community poisonings. Instead, we leverage a large, open vocabulary of thousands of words in order to fully characterize communities suffering from opioid poisoning, using a sample of 1.5 billion tweets from 6 million U.S. county mapped Twitter users. Results show that Twitter language predicted opioid poisoning mortality better than factors relating to socio-demographics, access to healthcare, physical pain, and psychological well-being. Additionally, risk factors revealed by the Twitter language analysis included negative emotions, discussions of long work hours, and boredom, whereas protective factors included resilience, travel/leisure, and positive emotions, dovetailing with results from the psychometric self-report data. The results show that natural language from public social media can be used as a surveillance tool for both predicting community opioid poisonings and understanding the dynamic social and psychological nature of the epidemic.
Biological 2,4,6-trinitrotoluene removal by extended aeration activated sludge: optimization using artificial neural network
Authors: Karimi Hossein , Mohammadi Farzaneh , Rajabi Saeed , Mahvi Amir Hossein , Ghanizadeh Ghader
Published: June 2023

Serious health issues can result from exposure to the nitrogenous pollutant like 2,4,6-trinitrotoluene (TNT), which is emitted into the environment by the munitions and military industries, as well as from TNT-contaminated wastewater. The TNT removal by extended aeration activated sludge (EAAS) was optimized in the current study using artificial neural network modeling. In order to achieve the best removal efficiency, 500 mg/L of chemical oxygen demand (COD), 4 and 6 h of hydraulic retention time (HRT), and 1–30 mg/L of TNT were used in this study. The kinetics of TNT removal by the EAAS system were described by the calculation of the kinetic coefficients K, Ks, Kd, max, MLSS, MLVSS, F/M, and SVI. Adaptive neuro fuzzy inference system (ANFIS) and genetic algorithms (GA) were used to optimize the data obtained through TNT elimination. ANFIS approach was used to analyze and interpret the given data, and its accuracy was around 97.93%. The most effective removal efficiency was determined using the GA method. Under ideal circumstances (10 mg/L TNT concentration and 6 h), the TNT removal effectiveness of the EAAS system was 84.25%. Our findings demonstrated that the artificial neural network system (ANFIS)-based EAAS optimization could enhance the effectiveness of TNT removal. Additionally, it can be claimed that the enhanced EAAS system has the ability to extract wastewaters with larger concentrations of TNT as compared to earlier experiments.
Gold nanoparticle decorated post-synthesis modified UiO-66-NH2 for A3-coupling preparation of propargyl amines
Authors: Mohammadi Leila , Taghavi Reza , Hosseinifard Mojtaba , Vaezi Mohammad Reza , Rostamnia Sadegh
Published: June 2023

In this report, the novel UiO‑66‑NH2based-MOF(Zr) catalytic system which further modified with nitrogen-rich organic ligand (5-aminotetrazole) using post synthetic modification (PSM) approach has been prepared here as an efficient catalyst to promote the A3-coupling preparation of propargyl amines in green aquatic media. This newly highly efficient catalyst was synthesized upon Zr-based MOF (UiO‑66‑NH2) which successfully functionalized with 2,4,6‑trichloro‑1,3,5‑triazine (TCT) and 5‑aminotetrazole, following through stabilization of gold metal (Au) nanopartilces. The addition ofN-rich organic ligand through post-synthesis modification which can be assisted to stabilize the bister and stable gold nanoparticles caused to unique structure of the final composite in favor of the progress of the A3coupling reaction. Also several strategies comprising XRD, FT-IR, SEM, BET, TEM, TGA, ICP, EDS and elemental mapping analyzes, were used to indicate the successful preparation of the UiO-66-NH2@ Cyanuric Chloride@ 5-amino tetrazole/Au-NPs. The results of productivity catalyst are accomplished in good to excellent yields for all sort of reactions under mild conditions which is a proof of superior activity heterogeneous catalyst containing Au-nanoparticles. In addition, the suggested catalyst represented excellent reusability with no remarkable loss in activity up 9 sequential runs.
A mechanistic interpretation of relativistic rigid body rotation
Authors: Catheline Stefan
Published: June 2023

The starting point of this manuscript is classical rigid body rotation. As it is well known, it contradicts basis of relativity since infinite speed is reached at infinite distance from the rotation center O. In order to fix this problem, a phenomenological circle-based construction using Euclidian trigonometry is first described: the relativistic rigid body rotation. The physical Eulerian acceleration implied by this geometrical construction then sketches future links with Maxwell’s equation and Lense-Thirring effect. More importantly, relativistic rigid body rotation is shown to be compatible with Lorentz transformation and brings new geometrical interpretations of time and space intervals.
Overexpression of fatty acid synthase attenuates bleomycin induced lung fibrosis by restoring mitochondrial dysfunction in mice
Authors: Shin Hyesun , Park Shinhee , Hong Jisu , Baek Ae-Rin , Lee Junehyuk , Kim Do-Jin , Jang An-Soo , Chin Su Sie , Jeong Sung Hwan , Park Sung-Woo
Published: June 2023

Proper lipid metabolism is crucial to maintain alveolar epithelial cell (AEC) function, and excessive AEC death plays a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The mRNA expression of fatty acid synthase (FASN), a key enzyme in the production of palmitate and other fatty acids, is downregulated in the lungs of IPF patients. However, the precise role of FASN in IPF and its mechanism of action remain unclear. In this study, we showed that FASN expression is significantly reduced in the lungs of IPF patients and bleomycin (BLM)-treated mice. Overexpression of FASN significantly inhibited BLM-induced AEC death, which was significantly potentiated by FASN knockdown. Moreover, FASN overexpression reduced BLM-induced loss of mitochondrial membrane potential and the production of mitochondrial reactive oxygen species (ROS). Oleic acid, a fatty acid component increased by FASN overexpression, inhibited BLM-induced cell death in primary murine AECs and rescue BLM induced mouse lung injury/fibrosis. FASN transgenic mice exposed to BLM exhibited attenuated lung inflammation and collagen deposition compared to controls. Our findings suggest that defects in FASN production may be associated with the pathogenesis of IPF, especially mitochondrial dysfunction, and augmentation of FASN in the lung may have therapeutic potential in preventing lung fibrosis.
Robust-stein estimator for overcoming outliers and multicollinearity
Authors: Lukman Adewale F. , Farghali Rasha A. , Kibria B. M. Golam , Oluyemi Okunlola A.
Published: June 2023

Linear regression models with correlated regressors can negatively impact the performance of ordinary least squares estimators. The Stein and ridge estimators have been proposed as alternative techniques to improve estimation accuracy. However, both methods are non-robust to outliers. In previous studies, the M-estimator has been used in combination with the ridge estimator to address both correlated regressors and outliers. In this paper, we introduce the robust Stein estimator to address both issues simultaneously. Our simulation and application results demonstrate that the proposed technique performs favorably compared to existing methods.
Salmonella T3SS effector SseK1 arginine-glycosylates the two-component response regulator OmpR to alter bile salt resistance
Authors: Hasan Md Kamrul , Scott Nichollas E. , Hays Michael P. , Hardwidge Philip R. , El Qaidi Samir
Published: June 2023

Type III secretion system (T3SS) effector proteins are primarily recognized for binding host proteins to subvert host immune response during infection. Besides their known host target proteins, several T3SS effectors also interact with endogenous bacterial proteins. Here we demonstrate that the Salmonella T3SS effector glycosyltransferase SseK1 glycosylates the bacterial two-component response regulator OmpR on two arginine residues, R15 and R122. Arg-glycosylation of OmpR results in reduced expression of ompF, a major outer membrane porin gene. Glycosylated OmpR has reduced affinity to the ompF promoter region, as compared to the unglycosylated form of OmpR. Additionally, the Salmonella ΔsseK1 mutant strain had higher bile salt resistance and increased capacity to form biofilms, as compared to WT Salmonella, thus linking OmpR glycosylation to several important aspects of bacterial physiology.
Establishment of cancer-associated fibroblasts-related subtypes and prognostic index for prostate cancer through single-cell and bulk RNA transcriptome
Authors: Qian Youliang , Feng Dechao , Wang Jie , Wei Wuran , Wei Qiang , Han Ping , Yang Lu
Published: June 2023

Current evidence indicate that cancer-associated fibroblasts (CAFs) play an important role in prostate cancer (PCa) development and progression. In this study, we identified CAF-related molecular subtypes and prognostic index for PCa patients undergoing radical prostatectomy through integrating single-cell and bulk RNA sequencing data. We completed analyses using software R 3.6.3 and its suitable packages. Through single-cell and bulk RNA sequencing analysis, NDRG2, TSPAN1, PTN, APOE, OR51E2, P4HB, STEAP1 and ABCC4 were used to construct molecular subtypes and CAF-related gene prognostic index (CRGPI). These genes could clearly divide the PCa patients into two subtypes in TCGA database and the BCR risk of subtype 1 was 13.27 times higher than that of subtype 2 with statistical significance. Similar results were observed in MSKCC2010 and GSE46602 cohorts. In addtion, the molucular subtypes were the independent risk factor of PCa patients. We orchestrated CRGPI based on the above genes and divided 430 PCa patients in TCGA database into high- and low- risk groups according to the median value of this score. We found that high-risk group had significant higher risk of BCR than low-risk group (HR: 5.45). For functional analysis, protein secretion was highly enriched in subtype 2 while snare interactions in vesicular transport was highly enriched in subtype 1. In terms of tumor heterogeneity and stemness, subtype 1 showd higher levels of TMB than subtype 2. In addition, subtype 1 had significant higher activated dendritic cell score than subtype 2. Based on eight CAF-related genes, we developed two prognostic subtypes and constructed a gene prognostic index, which could predict the prognosis of PCa patients very well.
Asymmetric lung increases particle filtration by deposition
Authors: Kundu Debjit , Panchagnula Mahesh V.
Published: June 2023

Human lung is known to be an asymmetric dichotomously branched network of bronchioles. Existing literature on the relation between anatomy and air-flow physics in the tracheobronchial trees has discussed the results of asymmetry. We discuss a secondary (but an important) lung function to seek asymmetry: to protect the acinus from a high pathogen load. We build morphometric parameter-based mathematical models of realistic bronchial trees to explore the structure-function relationship. We observe that maximum surface area for gas exchange, minimum resistance and minimum volume are obtained near the symmetry condition. In contrast, we show that deposition of inhaled foreign particles in the non-terminal airways is enhanced by asymmetry. We show from our model, that the optimal value of asymmetry for maximum particle filtration is within 10% of the experimentally measured value in human lungs. This structural trait of the lung aids in self-defence of the host against pathogen laden aerosols. We explain how natural asymmetric design of typical human lungs makes a sacrifice away from gas exchange optimality to gain this protection. In a typical human lung, when compared to most optimal condition (which is associated with symmetric branching), the fluidic resistance is 14% greater, the gas exchange surface area is about 11% lower, the lung volume is about 13% greater to gain an increase of 4.4% protection against foreign particles. This afforded protection is also robust to minor variations in branching ratio or variation in ventilation, which are both crucial to survival.
Origin, genetic structure and evolutionary potential of the natural hybrid Ranunculus circinatus × R. fluitans
Authors: Zalewska-Gałosz J. , Kwiatkowska M. , Prančl J. , Skubała K. , Lučanová M. , Gebler D. , Szoszkiewicz K.
Published: June 2023

Understanding the genetic variability of hybrids provides information on their current and future evolutionary role. In this paper, we focus on the interspecific hybridRanunculus circinatus × R. fluitansthat forms spontaneously within the groupRanuculusL. sect.BatrachiumDC. (Ranunculaceae Juss.). Genome-wide DNA fingerprinting using amplified fragment length polymorphisms (AFLP) was employed to determine the genetic variation among 36 riverine populations of the hybrid and their parental species. The results demonstrate a strong genetic structure ofR. circinatus × R. fluitanswithin Poland (Central Europe), which is attributed to independent hybridization events, sterility of hybrid individuals, vegetative propagation, and isolation through geographical distance within populations. The hybridR. circinatus × R. fluitansis a sterile triploid, but, as we have shown in this study, it may participate in subsequent hybridization events, resulting in a ploidy change that can lead to spontaneous fertility recovery. The ability to produce unreduced female gametes of the hybridR. circinatus × R. fluitansand the parental speciesR. fluitansis an important evolutionary mechanism inRanunculussect.Batrachiumthat could give rise to new taxa.
Personal sustained cooperation based on networked evolutionary game theory
Authors: Yan Jun
Published: June 2023

Evolutionary game theory on complex networks provides an effective theoretical tool to explain the emergence of sustained cooperative behavior. Human society has formed various organizational networks. The network structure and individual behavior take on a variety of forms. This diversity provides the basis for choice, so it is crucial for the emergence of cooperation. This article provides a dynamic algorithm for individual network evolution, and calculates the importance of different nodes in the network evolution process. In the dynamic evolution simulation, the probability of the cooperation strategy and betrayal strategy is described. In the individual interaction network, cooperative behavior will promote the continuous evolution of individual relationships and form a better aggregative interpersonal network. The interpersonal network of betrayal has been in a relatively loose state, and its continuity must rely on the participation of new nodes, but there will be certain "weak links" in the existing nodes of the network.