bluuebunny/crossref_metadata_2025 huggingface dataset:
Inter-organisational Cooperation Oriented Towards Sustainability Involving SMEs: a Systematic Literature Review
Authors: Suchek Nathalia , Franco Mário
Published: March 2023

Small and medium-sized enterprises (SME) are under increasing pressure to implement sustainability practices and collaborate in sustainable development. To do so, they can choose to collaborate with other organisations in order to overcome the challenges and barriers found in moving towards sustainability. Sustainability issues in SMEs have been discussed in the last two decades, but the knowledge on the inter-organisational collaboration towards sustainability remains dispersed. In this sense, this paper aims to answer the question: what is known about inter-organisational cooperation oriented towards sustainability involving SMEs? A systematic literature review (SLR) was carried out using 55 articles available on Web of Science (WoS) aiming to understand the processes of inter-organisational relations towards sustainability involving SMEs, simultaneously addressing the emergence of the circular economy. As a result, the articles were organised into four groups, namely (1) cooperation for sustainability promoted by government initiatives, (2) effects of inter-organisational cooperation for sustainability, (3) process of cooperation oriented towards sustainability, and (4) start of discussions on cooperation for the circular economy. A framework is presented with an overview of the evolution of the field, highlighting the main factors and outcomes related to inter-organisational cooperation involving SMEs for sustainability. The review provides theoretical implications as future research avenues for academics and scholars as well as practical implications for entrepreneurs, managers and policy-makers.
Gender dynamics on Twitter during the 2020 U.S. Democratic presidential primary
Authors: King Catherine , Carley Kathleen M.
Published: March 2023

The Twitter social network for each of the top five U.S. Democratic presidential candidates in 2020 was analyzed to determine if there were any differences in the treatment of the candidates. This data set was collected from discussions of the presidential primary between December 2019 through April 2020. It was then separated into five sets,  one for each candidate. We found that the most discussed candidates, President Biden and Senator Sanders, received by far the most engagement from verified users and news agencies even before the Iowa caucuses, which was ultimately won by Mayor Buttigieg. The most popular candidates were also generally targeted more frequently by bots, trolls, and other aggressive users. However, the abusive language targeting the top two female candidates, Senators Warren and Klobuchar, included slightly more gendered and sexist language compared with the other candidates. Additionally, sexist slurs that ordinarily describe women were used more frequently than male slurs in all candidate data sets. Our results indicate that there may still be an undercurrent of sexist stereotypes permeating the social media conversation surrounding female U.S. presidential candidates.
Defining Trade Secrets in the United States: Past and Present Challenges – A Way Forward?
Authors: Nashkova Suzana
Published: March 2023

When approaching an analysis of a particular area of law, one must initially locate and understand the definition of its core concept. Yet in trade secret law serious obstacles impede the process. Unlike other intellectual property (IP) regimes, such as copyright and patent law, the core concepts of which are subject to unitary definitions governed by international treaties or domestic statutes, the trade secret concept has received no parallel treatment and, until recently in the United States, remained mainly defined under common law. Subtle differences in the way trade secrets were judicially conceived often generated conflicts between courts, opening the door for the application of divergent rules on similar points. This confusing background prompted the individual U.S. jurisdictions to gradually orient towards implementing statutory provisions in defining trade secrets. Despite the fact that U.S. trade secret law has since seen several statutory interventions at state and federal level, the precise meaning and definitional parameters of the concept remain elusive. This paper probes the existing trade secret definitions applicable in the U.S. via analysis of the divergent sources of law that underscored their formulation from the past until the present and identifies the challenges pertinent to their application in practice. Its aim is to analyze and compare these legal sources: first, to determine whether the current definition for the concept of a trade secret is adequate, or whether perhaps the existence of the multi-tier system impedes a party’s ability to identify trade secrets in a cross-border context; and second, to investigate whether a unanimously accepted definition under a pre-emptive statute complementary to one under an elaborated internationally binding treaty might remedy this issue.
Characteristics and outcomes of hospital-acquired and community-acquired peritonitis in patients on peritoneal dialysis: a retrospective cohort study
Authors: Ling Chau Wei , Sud Kamal , Peterson Gregory , Fethney Judith , Van Connie , Patel Rahul , Zaidi Syed Tabish Razi , Castelino Ronald
Published: March 2023

Background

Peritonitis remains a significant complication of peritoneal dialysis. However, there is limited information on the clinical characteristics and outcomes of hospital-acquired peritonitis compared to community-acquired peritonitis in patients undergoing peritoneal dialysis. Furthermore, the microbiology and outcomes of community-acquired peritonitis may vary from hospital-acquired peritonitis. Therefore, the aim was to gather and analyse data to address this gap.

Methods

Retrospective review of the medical records of all adult patients on peritoneal dialysis within the peritoneal dialysis units in four university teaching hospitals in Sydney, Australia, who developed peritonitis between January 2010 and November 2020. We compared the clinical characteristics, microbiology and outcomes of community-acquired peritonitis and hospital-acquired peritonitis. Community acquired peritonitis was defined as the development of peritonitis in the outpatient setting. Hospital-acquired peritonitis was defined as: (1) developed peritonitis anytime during hospitalisation for any medical condition other than peritonitis, (2) diagnosed with peritonitis within 7 days of hospital discharge and developed symptoms of peritonitis within 3 days of the hospital discharge.

Results

Overall, 904 episodes of peritoneal dialysis-associated peritonitis were identified in 472 patients, of which 84 (9.3%) episodes were hospital-acquired. Patients with hospital-acquired peritonitis had lower mean serum albumin levels compared to those with community-acquired peritonitis(22.95 g/L vs. 25.76 g/L, p = 0.002). At the time of diagnosis, lower median peritoneal effluent leucocyte and polymorph counts were observed with hospital-acquired peritonitis compared to community-acquired peritonitis (1236.00/mm3 vs. 3183.50/mm3, p < 0.01 and 1037.00/mm3 vs. 2800.00/mm3, p < 0.01, respectively). Higher proportions of peritonitis due to Pseudomonas spp. (9.5% vs. 3.7%, p = 0.020) and vancomycin-resistant Enterococcus (2.4% vs. 0.0%, p = 0.009), lower rates of complete cure (39.3% vs. 61.7%, p < 0.001), higher rates of refractory peritonitis (39.3% vs. 16.4%, p < 0.001) and higher all-cause mortality within 30 days of peritonitis diagnosis (28.6% vs. 3.3%, p < 0.001) were observed in the hospital-acquired peritonitis group compared to the community-acquired peritonitis group, respectively.

Conclusions

Despite having lower peritoneal dialysis effluent leucocyte counts at the time of diagnosis, patients with hospital-acquired peritonitis had poorer outcomes, including lower rates of complete cure, higher rates of refractory peritonitis and higher rates of all-cause mortality within 30 days of diagnosis, compared to those with community-acquired peritonitis.

Graphic abstract
Disrupting the cycle of youth violence: The role of social support for youth in a Northern Irish Youth Work Programme
Authors: Walsh Colm
Published: March 2023

Youth violence is a significant concern and previous research has found that violence is both trauma inducing and violence inducing. Meta-analyses have demonstrated that peri-trauma contextual factors such as the presence or absence of social supports following the onset of trauma may be predictive of the onset and duration of psychological stress. The aim of this study is to build upon the existing research evidence to clarify the links between social support, psychological stress and physical violence among a cross-section of youth living in high-violence areas of Northern Ireland. Participants were a sample of 10–25-year-olds (N = 635) who participated in a targeted youth work programme in Northern Ireland. This study conducted a mediation analysis, entering social support as the independent variable, psychological distress as the mediator and self-reported violence as the outcome variable. Violent victimisation was entered as a covariate in the analysis. After controlling for violent victimisation, social support operates through psychological stress to influence the risk of physical violence. Social support may contribute to reductions in psychological stress and thus buffer against the risks of living in areas of elevated community violence. Specialist youth work approaches may provide an opportunity to reduce psychological stress and thus help to mitigate the risk of further violence. Combined, these insights provide opportunities for harm reduction and prevention. At the same time, these findings advance our understanding of the distinct mechanisms of change involved in youth work-led violence prevention efforts.
Coupling of Liquid and Surface Chemistry in Urea SCR Systems
Authors: Kuntz Christian , Jägerfeld Paul Jakob , Mmbaga Joe , Hayes Robert E. , Deutschmann Olaf
Published: March 2023

Close-coupled selective catalytic reduction (SCR) systems are one method to deal with tightening emission legislation for NOxin internal combustion engines. Due to smaller mixing sections and at unfavourable boundary conditions, however, urea-water solution (UWS) droplets can impact on the SCR catalyst itself. To investigate this phenomenon further, this work develops a modeling capability of this process. Established mechanism for NH3-SCR and HNCO hydrolysis from literature is integrated into DETCHEMCHANNELand a 2D COMSOL model to simulate the influence in the SCR Channel. Simulations are validated against end-of-pipe experiments from literature and spatially resolved concentration profiles from a hot gas test rig with very good agreement. Finally, a channel simulation is coupled with a model to describe the catalytic decomposition of an urea droplet. The coupled simulation is able to simulate the influence of UWS droplet impact onto a catalyst channel. Fast droplet decomposition causes a peak in NH3and HNCO in the single channel and thus increases NOxconversion. However, the overall uniformity and efficiency are decreased, which is why droplet impact on the catalyst should be strictly avoided.
Standardisation efforts of ISO/TC 261 “additive manufacturing” 20th plenary meeting of ISO/TC 261 “additive manufacturing”
Authors: Pei Eujin , Seidel Christian
Published: March 2023

The main objective of ISO/TC 261 is to standardise the processes of additive manufacturing, the process chains (Data, Materials, Processes, Hard- and Software, Applications), test procedures, quality parameters, supply agreements, environment, health and safety, fundamentals and vocabularies. This section provides readers with news regarding standardisation efforts of ISO/TC 261. Further up-to-date information regarding recently published documents, such as new standards and revised standards, the status of standards can be found in the ISO/TC261 webpages: https://www.iso.org/committee/629086.html and the committee webpages: https://committee.iso.org/sites/tc261/home/news.html.
Modular forms on $${{\,\textrm{SU}\,}}(2,1)$$ with weight $$\frac{1}{3}$$
Authors: Freitag Eberhard , Hill Richard M.
Published: March 2023

In this note, we describe several new examples of holomorphic modular forms on the group $${{\,\textrm{SU}\,}}(2,1)$$

SU

(
2
,
1
)

. These forms are distinguished by having weight $$\frac{1}{3}$$

1
3

. We also describe a method for determining the levels at which one should expect to find such fractional weight forms.
Integrated Inverse Dynamics and Optimized Mechanical Design in Underactuated Linear Vibratory Feeders Under Periodic Excitation
Authors: Bettega Jason , Richiedei Dario , Tamellin Iacopo , Trevisani Alberto
Published: March 2023

Purpose

This paper proposes an integrated method for optimizing the response of underactuated linear vibratory feeders operating in open-loop control, under generic periodic excitations. The goal is ensuring a uniform motion of the tray, despite the presence of less actuators than degrees of freedom and of several specifications of the desired motion.

Method

To cope with the underactuated nature of these systems and with their non-minimum phase behavior, dynamic structural modification and the inverse dynamics approach are properly integrated by exploiting a common definition of the system internal dynamics. In the inverse dynamics problem, the inverse dynamics is stabilized through output redefinition and the resulting ordinary differential equations are integrated to compute causal actuation forces, ensuring almost-exact tracking for as many coordinates as the number of actuators. The tracking of the remaining coordinates of interest is improved through a proper design of the mechanical parameters, based on the modification of the internal dynamics.

Results

The effectiveness of the proposed method is assessed through numerical simulations performed on the challenging case of a 14-degrees of freedom underactuated non-minimum phase linear vibratory feeder adopted in manufacturing plants to convey products.

Conclusion

The results evidence the benefits obtained by integrating structural modification together with inverse dynamics. Inverse dynamics is effective, since the tracking error on the imposed coordinates is negligible. On the other hand, the benefits introduced by dynamic structural modification are proved as well, by the reduction of the tracking error also for the non-imposed coordinates.
Oxidative degradation of sulfafurazole drug by chromium trioxide in different acidic media: a kinetic and mechanistic study
Authors: Fawzy Ahmed , Fawzi Arwa
Published: March 2023

Although antibiotics are fundamentally vital for treating human diseases, they became harmful to the ecosystem if they reach to the environment. Due to antibiotics are intensely vulnerable to oxidation, oxidation of antibiotics can be considered as a recognized tool for removal or degradation of antibiotics to save the humans and ecosystem. The existing research illuminates the kinetics of oxidative degradation of sulfafurazole antibiotic (SFZ) using chromium trioxide (CrO3) in both H2SO4 and HClO4 media. The reactions in both acidic media showed a 1: 1.33 ± 0.07 stoichiometry (SFZ: CrO3). The reliance of the rates of oxidation reactions on the reactants’ concentrations illuminated that the reactions were first order in [CrO3], whereas in [SFZ] and [H+], their orders were fractional-first and fractional-second, respectively. The rate of oxidation of SFZ in H2SO4 was discovered to be higher than that observed in HClO4. The oxidation rates were not influenced by the change in ionic strength (I) or dielectric constant (D). Addition of Cr(III) had not remarked effect on the rates. Free radical intervention tests were positive. The activation quantities were calculated then discussed. A conceivable mechanism of oxidation was anticipated. Furthermore, the rate-law expressions were also derived.
Survival Prediction Models for Ovarian Cancer Patients with Lung Metastasis: A Retrospective Cohort Study Based on SEER Database
Authors: Li Dingxi , Zhang Mengli , Zhang Huiying
Published: March 2023

To develop a random forest prediction model for the and short- and long-term survival of ovarian cancer patients with lung metastasis. This retrospective cohort study enrolled primary ovarian cancer patients with lung metastasis from the surveillance, epidemiology and end results (SEER) database (2010–2015). All eligible women were randomly divided into the training (n = 1357) and testing set (n = 582). The outcomes were 1-, 3- and 5-year survival. Predictive factors were screened by random forest analysis. The prediction models for predicting the 1-, 3- and 5-year survival were conducted using the training set, and the internal validation was carried out by the testing set. The performance of the models was evaluated with area under the curve (AUC), accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). The subgroups based on the pathological classification further assessed the model’s performance. Totally 1345 patients suffered from death within 5 years. The median follow-up was 7.00 (1.00, 21.00) months. Age at diagnosis, race, marital status, tumor size, tumor grade, TNM stage, brain metastasis, liver metastasis, bone metastasis, etc. were predictors. The AUCs of the prediction model for the 1-, 3-, 5-year survival in the testing set were 0.849 [95% confidence interval (CI): 0.820–0.884], 0.789 (95% CI 0.753–0.826) and 0.763 (95% CI 0.723–0.802), respectively. The results of subgroups on different pathological classifications showed that the AUCs of the model were over 0.7. This random forest model performed well predictive ability for the short- and long-term survival of ovarian cancer patients with lung metastasis, which may be beneficial to identify high-risk individuals for intelligent medical services.
Surgical management outcome in Fistula-in-ano: A cross-sectional study in Ethiopia
Authors: Bejiga Gosa , Adilo Abebe , Genemo Endris
Published: March 2023

Abstract

Introduction

Fistula-in-ano (FIA) is an abnormal communication between the rectum or anal canal and the perineal skin. Surgery is the mainstay of treatment having variable outcomes which can be affected by different factors. However, there is a lack of evidence regarding this in our setup. We aimed to assess the management outcome of FIA and its associated factors among surgically treated patients from August 5, 2016, to July 23, 2021.

Methods

We conducted a tertiary hospital-based, cross-sectional study from December 1, 2021, to January 28, 2022, among 108 patients operated on for FIA. Data were collected by reviewing patients’ medical records. Descriptive statistics and binary logistic regression models were applied to analyze the data. Adjusted odds ratio (AOR), with a 95% confidence interval (CI), was used to assess the strength of associations. A p-value of 0.05 was taken as a cutoff. The outcome was labeled favorable if the treatment was successful and unfavorable if it failed.

Results

Of 108 participants, men were more affected, with a male-to-female ratio of 5.8:1. The median age was 34y. The magnitude of the operative failure with its 95%CI was 8.3% (3.6%–13.6%). The operative failure rate was high in those with a previous history of surgery, AOR 13.2; with 95%CI (2.4–73.6), and high FIA, AOR 10.9; with 95%CI (1.4–82.2).

Conclusions

High FIA and previous history of surgery were the factors associated with the surgical outcome of FIA. A future large-scale study is needed to identify other associated factors.

Highlights
The Miracles of Our Lady of Rocamadour
Authors: Bull Marcus
Published: March 2023

Medieval miracle stories from a major pilgrim destination in twelfth-century France.
Pauli Murray: Human Rights Visionary and Trailblazer
Authors: Johnson Darin E. W. , Powell Catherine
Published: March 2023

While other scholars have discussed Dr. Pauli Murray's remarkable contributions to race and sex equality law,1 few, if any, have placed her contributions within the context of the broader tradition of human rights law. And yet, she identified herself specifically through this lens, using the terminology and law of human rights, in part shaped by her friendship with First Lady Eleanor Roosevelt, a delegate to the UN Drafting Committee for the Universal Declaration of Human Rights (UDHR).2 This essay addresses a lacuna in legal scholarship by exploring the ways in which Murray's work fits into the Black intellectual tradition concerning the human rights idea. It also seeks to provide a greater understanding concerning contributions to human rights (and more broadly, international law) made by Howard University School of Law, where she attended law school and one of us is on the faculty. Among other linkages, Clarence Clyde Ferguson, a dean of Howard Law School and former ambassador, was the first Black president of the American Society of International Law.
The Promotion of Health Literacy
Authors: Harzheim Laura , Lorke Mariya , Rostamzadeh Ayda , Jessen Frank , Woopen Christiane , Jünger Saskia
Published: March 2023

Abstract: Progress in predictive medicine has increased the challenges to navigating complex risk information for patients and healthcare professionals. This contribution investigates how people facing the risk of developing Alzheimer’s dementia perceive risk, what aspects are relevant to their health literacy, and how to promote individual health literacy in predictive medicine. We conducted a qualitative study analyzing narrative interviews, body maps, and sociodemographic data from persons who had undergone early predictive procedures in a memory clinic. We understand the promotion of health literacy as an ethical task in predictive medicine and argue for (1) emphasizing personal resources to promote subjective health literacy, (2) reframing communication and decision-making about disease risk, and (3) teaching skills for value-sensitive, individualized risk communication.
Tod und Sterben unterrichten
Authors: Kohnle Lisa-Marie , Brendebach Christine
Published: March 2023

Zusammenfassung: Der Artikel verdeutlicht, dass der Einsatz des szenischen Spiels bei emotionalen Themen, wie z.B. Tod und Sterben, gewinnbringend für die Lernenden sein kann. Es fördert das Erreichen von sozialen, personalen und emotionalen Kompetenzen. Es bietet den Auszubildenen die Möglichkeiten, sich selbst, ihre Mimik und Gestik, ihre Haltung und ihr Handeln zu erproben, zu überdenken und zu reflektieren.
Multi‐Model Subseasonal Prediction Skill Assessment of Water Vapor Transport Associated With Atmospheric Rivers Over the Western U.S.
Authors: Zhang Zhenhai , DeFlorio Michael J. , Delle Monache Luca , Subramanian Aneesh C. , Ralph F. Martin , Waliser Duane E. , Zheng Minghua , Guan Bin , Goodman Alexander , Molod Andrea M. , Vitart Frederic , Kumar Arun , Lin Hai
Published: March 2023

Subseasonal‐to‐seasonal (S2S) forecasts of atmospheric rivers (ARs) are in high demand in the water supply management and flood control communities. This study focuses on a new metric, the accumulated water vapor transport associated with ARs, which is closely related to the winter precipitation over the western U.S., and provides a multi‐model S2S prediction skill assessment. The prediction skill is evaluated at lead time 1–4 weeks in four dynamical model hindcast data sets from National Centers for Environmental Prediction (NCEP), European Center for Medium‐Range Weather Forecasts (ECMWF), Environment and Climate Change Canada (ECCC), and Global Modeling and Assimilation Office (GMAO) at National Aeronautics and Space Administration. Three reanalysis data sets are used to evaluate the uncertainty of prediction skills related to the choice of references. The AR‐related water vapor transport is underestimated in ECMWF and ECCC over most of the investigated region, while its maximum has a southeastward shift in NCEP and GMAO at lead time 3–4 weeks. The root mean square error, anomaly correlation coefficient, and Brier skill score are calculated to quantify the prediction skill in both deterministic and probabilistic sense. At week‐3 lead time, the models have significant skill near the lower latitudes (<40°N) of the eastern North Pacific, extending northeastward to the California coastal area. Models have higher skills in forecasting no and strong AR cases than weak cases. The Madden–Julian Oscillation can modulate the prediction skill at week‐3 lead over central and Southern California, but with large uncertainties across models.
Automated Symbolic Upscaling: 1. Model Generation for Extended Applicability Regimes
Authors: Pietrzyk Kyle , Battiato Ilenia
Published: March 2023

In porous media theory, upscaling techniques are fundamental to deriving rigorous Darcy‐scale models for flow and reactive transport in subsurface systems. Due to limitations in classical techniques, a number of ad hoc approaches have been proposed to address physical regimes in which reactive time scales are similar to, or faster than, diffusive time scales. In Part 1 of this two part series, we present a strategy for expanding the applicability of classical homogenization theory by generalizing the assumed closure form. We detail the implementation of this strategy on two reactive mass transport problems with moderately reactive physics. The strategy produces nontrivial homogenized models with emergent terms and effective parameters that couple reactive, diffusive, and advective transport. The differences in equation forms between the macroscopic and pore‐scale descriptions advise caution to further studies where the forms of macroscopic equations are assumed, as opposed to rigorously derived. Numerical validation is provided for each problem to show that the error estimates of homogenization theory are satisfied, and to justify the implemented strategy. In Part 2, the presented strategy is automated using symbolic computing to expedite its implementation.
Depressive symptoms and mortality – effect variation by body mass index: a prospective study in a primary care population
Authors: Rantanen Ansa Talvikki , Kautiainen Hannu , Korhonen Päivi Elina
Published: March 2023

Background/Objective

Pre-existing diseases have been found to affect the relationship between body mass index (BMI) and mortality. However, psychiatric disorders common in general population have not been previously addressed. The aim of this study was to assess the relationship of depressive symptoms and BMI with all-cause mortality.

Methods

A prospective cohort study in Finnish primary care setting was conducted. A population survey identified 3072 middle-aged subjects who had elevated cardiovascular risk. Subjects who attended clinical examination and completed Beck’s Depression Inventory (BDI) (n = 2509) were included in this analysis. Effect of depressive symptoms and BMI on all-cause mortality after 14 years follow-up was estimated in models adjusted for age, sex, education years, current smoking, alcohol use, physical activity, total cholesterol, systolic blood pressure, and glucose disorders.

Results

When subjects with and without increased depressive symptoms were compared, the fully adjusted hazard ratios (HR) for all-cause mortality in the BMI categories (<25.0, 25.0–29.9, 30.0–34.9, ≥35.0 kg/m2) were 3.26 (95% CI 1.83 to 5.82), 1.31 (95% CI 0.83 to 2.06), 1.27 (95% CI 0.76 to 2.11), and 1.25 (95% CI 0.63 to 2.48), respectively. The lowest risk of death was among non-depressive subjects who had BMI < 25.0 kg/m2.

Conclusions

Effect of increased depressive symptoms on all-cause mortality risk seems to vary with BMI. Elevated mortality risk is especially apparent among depressive subjects with normal weight. Among individuals with overweight and obesity, increased depressive symptoms seem not to further increase all-cause mortality.
mTORC1 signaling pathway regulates tooth repair
Authors: Liu Honghong , Yue Yu , Xu Zhiyun , Guo Li , Wu Chuan , Zhang Da , Luo Lingfei , Huang Wenming , Chen Hong , Yang Deqin
Published: March 2023

Tooth germ injury can lead to abnormal tooth development and even tooth loss, affecting various aspects of the stomatognathic system including form, function, and appearance. However, the research about tooth germ injury model on cellular and molecule mechanism of tooth germ repair is still very limited. Therefore, it is of great importance for the prevention and treatment of tooth germ injury to study the important mechanism of tooth germ repair by a tooth germ injury model. Here, we constructed a Tg(dlx2b:Dendra2-NTR) transgenic line that labeled tooth germ specifically. Taking advantage of the NTR/Mtz system, the dlx2b+ tooth germ cells were depleted by Mtz effectively. The process of tooth germ repair was evaluated by antibody staining, in situ hybridization, EdU staining and alizarin red staining. The severely injured tooth germ was repaired in several days after Mtz treatment was stopped. In the early stage of tooth germ repair, the expression of phosphorylated 4E-BP1 was increased, indicating that mTORC1 is activated. Inhibition of mTORC1 signaling in vitro or knockdown of mTORC1 signaling in vivo could inhibit the repair of injured tooth germ. Normally, mouse incisors were repaired after damage, but inhibition/promotion of mTORC1 signaling inhibited/promoted this repair progress. Overall, we are the first to construct a stable and repeatable repair model of severe tooth germ injury, and our results reveal that mTORC1 signaling plays a crucial role during tooth germ repair, providing a potential target for clinical treatment of tooth germ injury.
Angular momentum holography via a minimalist metasurface for optical nested encryption
Authors: Yang Hui , He Peng , Ou Kai , Hu Yueqiang , Jiang Yuting , Ou Xiangnian , Jia Honghui , Xie Zhenwei , Yuan Xiaocong , Duan Huigao
Published: March 2023

Metasurfaces can perform high-performance multi-functional integration by manipulating the abundant physical dimensions of light, demonstrating great potential in high-capacity information technologies. The orbital angular momentum (OAM) and spin angular momentum (SAM) dimensions have been respectively explored as the independent carrier for information multiplexing. However, fully managing these two intrinsic properties in information multiplexing remains elusive. Here, we propose the concept of angular momentum (AM) holography which can fully synergize these two fundamental dimensions to act as the information carrier, via a single-layer, non-interleaved metasurface. The underlying mechanism relies on independently controlling the two spin eigenstates and arbitrary overlaying them in each operation channel, thereby spatially modulating the resulting waveform at will. As a proof of concept, we demonstrate an AM meta-hologram allowing the reconstruction of two sets of holographic images, i.e., the spin-orbital locked and the spin-superimposed ones. Remarkably, leveraging the designed dual-functional AM meta-hologram, we demonstrate a novel optical nested encryption scheme, which is able to achieve parallel information transmission with ultra-high capacity and security. Our work opens a new avenue for optionally manipulating the AM, holding promising applications in the fields of optical communication, information security and quantum science.
Sperm quality metrics were improved by a biomimetic microfluidic selection platform compared to swim-up methods
Authors: Vasilescu Steven A. , Ding Lin , Parast Farin Yazdan , Nosrati Reza , Warkiani Majid Ebrahimi
Published: March 2023

Sperm selection is an essential component of all assisted reproductive treatments (ARTs) and is by far the most neglected step in the ART workflow in regard to technological innovation. Conventional sperm selection methodologies typically produce a higher total number of sperm with variable motilities, morphologies, and levels of DNA integrity. Gold-standard techniques, including density gradient centrifugation (DGC) and swim-up (SU), have been shown to induce DNA fragmentation through introducing reactive oxygen species (ROS) during centrifugation. Here, we demonstrate a 3D printed, biologically inspired microfluidic sperm selection device (MSSP) that utilizes multiple methods to simulate a sperms journey toward selection. Sperm are first selected based on their motility and boundary-following behavior and then on their expression of apoptotic markers, yielding over 68% more motile sperm than that of previously reported methods with a lower incidence of DNA fragmentation and apoptosis. Sperm from the MSSP also demonstrated higher motile sperm recovery after cryopreservation than that of SU or neat semen. Experiments were conducted side-by-side against conventional SU methods using human semen (n = 33) and showed over an 85% improvement in DNA integrity with an average 90% reduction in sperm apoptosis. These results that the platform is easy-to-use for sperm selection and mimics the biological function of the female reproductive tract during conception.
Dual-signal readout paper-based wearable biosensor with a 3D origami structure for multiplexed analyte detection in sweat
Authors: Cheng Yuemeng , Feng Shaoqing , Ning Qihong , Li Tangan , Xu Hao , Sun Qingwen , Cui Daxiang , Wang Kan
Published: March 2023

In this research, we design and implement a small, convenient, and noninvasive paper-based microfluidic sweat sensor that can simultaneously detect multiple key biomarkers in human sweat. The origami structure of the chip includes colorimetric and electrochemical sensing regions. Different colorimetric sensing regions are modified with specific chromogenic reagents to selectively identify glucose, lactate, uric acid, and magnesium ions in sweat, as well as the pH value. The regions of electrochemical sensing detect cortisol in sweat by molecular imprinting. The entire chip is composed of hydrophilically and hydrophobically treated filter paper, and 3D microfluidic channels are constructed by using folding paper. The thread-based channels formed after the hydrophilic and hydrophobic modifications are used to control the rate of sweat flow, which in turn can be used to control the sequence of reactions in the differently developing colored regions to ensure that signals of the best color can be captured simultaneously by the colorimetric sensing regions. Finally, the results of on-body experiments verify the reliability of the proposed sweat sensor and its potential for the noninvasive identification of a variety of sweat biomarkers.
HSV-1 cellular model reveals links between aggresome formation and early step of Alzheimer’s disease
Authors: Albaret Marie Alexandra , Textoris Julien , Dalzon Bastien , Lambert Jérémy , Linard Morgane , Helmer Catherine , Hacot Sabine , Ghayad Sandra E. , Ferréol Martial , Mertani Hichem C. , Diaz Jean-Jacques
Published: March 2023

Many studies highlight the potential link between the chronic degenerative Alzheimer’s disease and the infection by the herpes simplex virus type-1 (HSV-1). However, the molecular mechanisms making possible this HSV-1-dependent process remain to be understood. Using neuronal cells expressing the wild type form of amyloid precursor protein (APP) infected by HSV-1, we characterized a representative cellular model of the early stage of the sporadic form of the disease and unraveled a molecular mechanism sustaining this HSV-1- Alzheimer’s disease interplay. Here, we show that HSV-1 induces caspase-dependent production of the 42 amino-acid long amyloid peptide (Aβ42) oligomers followed by their accumulation in neuronal cells. Aβ42 oligomers and activated caspase 3 (casp3A) concentrate into intracytoplasmic structures observed in Alzheimer’s disease neuronal cells called aggresomes. This casp3A accumulation in aggresomes during HSV-1 infection limits the execution of apoptosis until its term, similarly to an abortosis-like event occurring in Alzheimer’s disease neuronal cells patients. Indeed, this particular HSV-1 driven cellular context, representative of early stages of the disease, sustains a failed apoptosis mechanism that could explain the chronic amplification of Aβ42 production characteristic of Alzheimer’s disease patients. Finally, we show that combination of flurbiprofen, a non-steroidal anti-inflammatory drug (NSAID), with caspase inhibitor reduced drastically HSV-1-induced Aβ42 oligomers production. This provided mechanistic insights supporting the conclusion of clinical trials showing that NSAIDs reduced Alzheimer’s disease incidence in early stage of the disease. Therefore, from our study we propose that caspase-dependent production of Aβ42 oligomers together with the abortosis-like event represents a vicious circle in early Alzheimer’s disease stages leading to a chronic amplification of Aβ42 oligomers that contributes to the establishment of degenerative disorder like Alzheimer’s disease in patients infected by HSV-1. Interestingly this process could be targeted by an association of NSAID with caspase inhibitors.
Immuno-regulatory malignant B cells contribute to Chronic Lymphocytic Leukemia progression
Authors: Mékinian Arsène , Quinquenel Anne , Belkacem Koceïla Ait , Kanoun Feriel , Dondi Elisabetta , Franck Emilie , Boubaya Marouane , Mhibik Maïssa , Baran-Marszak Fanny , Letestu Rémi , Ajchenbaum-Cymbalista Florence , Lévy Vincent , Varin-Blank Nadine , Le Roy Christine
Published: March 2023

Chronic Lymphocytic Leukemia (CLL) is a heterogeneous B cell neoplasm ranging from indolent to rapidly progressive disease. Leukemic cell subsets with regulatory properties evade immune clearance; however, the contribution of such subsets during CLL progression is not completely elucidated. Here, we report that CLL B cells crosstalk with their immune counterparts, notably by promoting the regulatory T (Treg) cell compartment and shaping several helper T (Th) subsets. Among various constitutively- and BCR/CD40-mediated factors secreted, tumour subsets co-express two important immunoregulatory cytokines, IL10 and TGFβ1, both associated with a memory B cell phenotype. Neutralizing secreted IL10 or inhibiting the TGFβ signalling pathway demonstrated that these cytokines are mainly involved in Th- and Treg differentiation/maintenance. In line with the regulatory subsets, we also demonstrated that a CLL B cell population expresses FOXP3, a marker of regulatory T cells. Analysis of IL10, TGFβ1 and FOXP3 positive subpopulations frequencies in CLL samples discriminated 2 clusters of untreated CLL patients that were significantly different in Tregs frequency and time-to-treatment. Since this distinction was pertinent to disease progression, the regulatory profiling provides a new rationale for patient stratification and sheds light on immune dysfunction in CLL.
Blocking dPerk in the intestine suppresses neurodegeneration in a Drosophila model of Parkinson’s disease
Authors: Popovic Rebeka , Mukherjee Amrita , Leal Nuno Santos , Morris Lydia , Yu Yizhou , Loh Samantha H. Y. , Miguel Martins L.
Published: March 2023

Parkinson’s disease (PD) is characterised by selective death of dopaminergic (DA) neurons in the midbrain and motor function impairment. Gastrointestinal issues often precede motor deficits in PD, indicating that the gut-brain axis is involved in the pathogenesis of this disease. The features of PD include both mitochondrial dysfunction and activation of the unfolded protein response (UPR) in the endoplasmic reticulum (ER). PINK1 is a mitochondrial kinase involved in the recycling of defective mitochondria, and PINK1 mutations cause early-onset PD. Like PD patients, pink1 mutant Drosophila show degeneration of DA neurons and intestinal dysfunction. These mutant flies also lack vital proteins due to sustained activation of the kinase R-like endoplasmic reticulum kinase (dPerk), a kinase that induces the UPR. Here, we investigated the role of dPerk in intestinal dysfunction. We showed that intestinal expression of dPerk impairs mitochondrial function, induces cell death, and decreases lifespan. We found that suppressing dPerk in the intestine of pink1-mutant flies rescues intestinal cell death and is neuroprotective. We conclude that in a fly model of PD, blocking gut-brain transmission of UPR-mediated toxicity, is neuroprotective.
The translational revolution in atopic dermatitis: the paradigm shift from pathogenesis to treatment
Authors: Facheris Paola , Jeffery Jane , Del Duca Ester , Guttman-Yassky Emma
Published: March 2023

Atopic dermatitis (AD) is the most common inflammatory skin disease, and it is considered a complex and heterogeneous condition. Different phenotypes of AD, defined according to the patient age at onset, race, and ethnic background; disease duration; and other disease characteristics, have been recently described, underlying the need for a personalized treatment approach. Recent advancements in understanding AD pathogenesis resulted in a real translational revolution and led to the exponential expansion of the therapeutic pipeline. The study of biomarkers in clinical studies of emerging treatments is helping clarify the role of each cytokine and immune pathway in AD and will allow addressing the unique immune fingerprints of each AD subset. Personalized medicine will be the ultimate goal of this targeted translational research. In this review, we discuss the changes in the concepts of both the pathogenesis of and treatment approach to AD, highlight the scientific rationale behind each targeted treatment and report the most recent clinical efficacy data.
Reference compounds for characterizing cellular injury in high-content cellular morphology assays
Authors: Dahlin Jayme L. , Hua Bruce K. , Zucconi Beth E. , Nelson Shawn D. , Singh Shantanu , Carpenter Anne E. , Shrimp Jonathan H. , Lima-Fernandes Evelyne , Wawer Mathias J. , Chung Lawrence P. W. , Agrawal Ayushi , O’Reilly Mary , Barsyte-Lovejoy Dalia , Szewczyk Magdalena , Li Fengling , Lak Parnian , Cuellar Matthew , Cole Philip A. , Meier Jordan L. , Thomas Tim , Baell Jonathan B. , Brown Peter J. , Walters Michael A. , Clemons Paul A. , Schreiber Stuart L. , Wagner Bridget K.
Published: March 2023

Robust, generalizable approaches to identify compounds efficiently with undesirable mechanisms of action in complex cellular assays remain elusive. Such a process would be useful for hit triage during high-throughput screening and, ultimately, predictive toxicology during drug development. Here we generate cell painting and cellular health profiles for 218 prototypical cytotoxic and nuisance compounds in U-2 OS cells in a concentration-response format. A diversity of compounds that cause cellular damage produces bioactive cell painting morphologies, including cytoskeletal poisons, genotoxins, nonspecific electrophiles, and redox-active compounds. Further, we show that lower quality lysine acetyltransferase inhibitors and nonspecific electrophiles can be distinguished from more selective counterparts. We propose that the purposeful inclusion of cytotoxic and nuisance reference compounds such as those profiled in this resource will help with assay optimization and compound prioritization in complex cellular assays like cell painting.
Hypomorphic Brca2 and Rad51c double mutant mice display Fanconi anemia, cancer and polygenic replication stress
Authors: Tomaszowski Karl-Heinz , Roy Sunetra , Guerrero Carolina , Shukla Poojan , Keshvani Caezaan , Chen Yue , Ott Martina , Wu Xiaogang , Zhang Jianhua , DiNardo Courtney D. , Schindler Detlev , Schlacher Katharina
Published: March 2023

The prototypic cancer-predisposition disease Fanconi Anemia (FA) is identified by biallelic mutations in any one of twenty-three FANC genes. Puzzlingly, inactivation of one Fanc gene alone in mice fails to faithfully model the pleiotropic human disease without additional external stress. Here we find that FA patients frequently display FANC co-mutations. Combining exemplary homozygous hypomorphic Brca2/Fancd1 and Rad51c/Fanco mutations in mice phenocopies human FA with bone marrow failure, rapid death by cancer, cellular cancer-drug hypersensitivity and severe replication instability. These grave phenotypes contrast the unremarkable phenotypes seen in mice with single gene-function inactivation, revealing an unexpected synergism between Fanc mutations. Beyond FA, breast cancer-genome analysis confirms that polygenic FANC tumor-mutations correlate with lower survival, expanding our understanding of FANC genes beyond an epistatic FA-pathway. Collectively, the data establish a polygenic replication stress concept as a testable principle, whereby co-occurrence of a distinct second gene mutation amplifies and drives endogenous replication stress, genome instability and disease.
A generalizable nanopore sensor for highly specific protein detection at single-molecule precision
Authors: Ahmad Mohammad , Ha Jeung-Hoi , Mayse Lauren A. , Presti Maria F. , Wolfe Aaron J. , Moody Kelsey J. , Loh Stewart N. , Movileanu Liviu
Published: March 2023

Protein detection has wide-ranging implications in molecular diagnostics. Substantial progress has been made in protein analytics using nanopores and the resistive-pulse technique. Yet, a long-standing challenge is implementing specific interfaces for detecting proteins without the steric hindrance of the pore interior. Here, we formulate a class of sensing elements made of a programmable antibody-mimetic binder fused to a monomeric protein nanopore. This way, such a modular design significantly expands the utility of nanopore sensors to numerous proteins while preserving their architecture, specificity, and sensitivity. We prove the power of this approach by developing and validating nanopore sensors for protein analytes that drastically vary in size, charge, and structural complexity. These analytes produce unique electrical signatures that depend on their identity and quantity and the binder-analyte assembly at the nanopore tip. The outcomes of this work could impact biomedical diagnostics by providing a fundamental basis for biomarker detection in biofluids.
TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport
Authors: Canty John T. , Hensley Andrew , Aslan Merve , Jack Amanda , Yildiz Ahmet
Published: March 2023

Mitochondrial transport along microtubules is mediated by Miro1 and TRAK adaptors that recruit kinesin-1 and dynein-dynactin. To understand how these opposing motors are regulated during mitochondrial transport, we reconstitute the bidirectional transport of Miro1/TRAK along microtubules in vitro. We show that the coiled-coil domain of TRAK activates dynein-dynactin and enhances the motility of kinesin-1 activated by its cofactor MAP7. We find that TRAK adaptors that recruit both motors move towards kinesin-1’s direction, whereas kinesin-1 is excluded from binding TRAK transported by dynein-dynactin, avoiding motor tug-of-war. We also test the predictions of the models that explain how mitochondrial transport stalls in regions with elevated Ca2+. Transport of Miro1/TRAK by kinesin-1 is not affected by Ca2+. Instead, we demonstrate that the microtubule docking protein syntaphilin induces resistive forces that stall kinesin-1 and dynein-driven motility. Our results suggest that mitochondrial transport stalls by Ca2+-mediated recruitment of syntaphilin to the mitochondrial membrane, not by disruption of the transport machinery.