bluuebunny/crossref_metadata_2025 huggingface dataset:
Impella 5.5 Bridge to Heart Transplant: An Institutional Series and a Closer Look at Device Removal Technique
Authors: Clothier Jessica S. , Kobsa Serge , Praeger Jonathan , Bojko Markian , Dhillon Anahat , Vaidya Ajay , Lee Raymond
Published: March 2024

Limited donor organ availability often necessitates mechanical circulatory support, and recently the Impella 5.5, as a bridge to heart transplant. Of 175 Impella 5.5-supported patients at our institution, 45 underwent transplantation in the largest series to date, for whom we analyzed outcomes. Two methods of complete device explant were evaluated: central Impella transection and removalviaaxillary graft. Median Impella days were 25 (16–41); median waitlist days were 21 (9–37). Eighty-nine percent (40/45) of patients had device placementviaright axillary artery. Seventy-six percent (34/45) underwent central transection for device removal. Four patients (8.9%) required short-term venoarterial extracorporeal membranous oxygenation (VA ECMO) postoperatively for primary graft dysfunction (PGD). Two patients (4.4%) suffered postoperative stroke. Five patients (11.1%) required new RRT postoperatively. One patient (2.2%) returned to the operating room (OR) for axillary graft bleeding. A higher chance of procedural complications was found with the axillary removal technique (p= 0.014). Median intensive care unit (ICU) days, length of stay (LOS), and postoperative days to discharge were 46 (35–63), 59 (49–80), and 18 (15–24), respectively. Ninety-eight percent (44/45) survived to discharge. Thirty-day survival was 95.6% (43/45), with 1 year survival at 90.3% (28/31). Eighty-eight percent (37/42) remain without rejection. In our institutional experience, Impella 5.5 is a safe and reliable bridge to transplant.
Determination of Maximum Tolerable Cold Ischemia Time in a Mouse Model of Cervical Heterotopic Uterus Transplantation
Authors: Luo Xin , Yu Shengnan , Liu Bing , Zheng Qisheng , Zhou Xin , An Ke , Zhong Jiaying , Wu Licheng , Dai Helong , Qi Zhongquan , Xia Junjie
Published: March 2024

Background.

Uterus transplantation (UTx) is an emerging treatment for uterine factor infertility. Determining the maximum tolerable cold ischemia time is crucial for successful UTx. However, the limit for cold ischemia in the uterus is unclear. This study aimed to examine cold ischemia’s effects on mouse uteri and identify the maximum cold ischemia duration that uteri can endure.

Methods.

We systematically assessed the tolerance of mouse uteri to extended cold ischemia, 24 h, 36 h, and 48 h, using the cervical heterotopic UTx model. Multiple indicators were used to evaluate ischemia-reperfusion injury, including reperfusion duration, macroscopic examination, oxidative stress, inflammation, and histopathology. The function of transplants was evaluated through estrous cycle monitoring and embryo transfer.

Results.

Mouse uteri subjected to 48 h of cold ischemia exhibited significant delays and insufficiencies in reperfusion, substantial tissue necrosis, and loss of the estrous cycle. Conversely, uteri that underwent cold ischemia within 36 h showed long survival, regular estrous cycles, and fertility.

Conclusions.

Our study demonstrated that mouse uteri can endure at least 36 h of cold ischemia, extending the known limits for cold ischemia and providing a pivotal reference for research on the prevention and treatment of cold ischemic injury in UTx.
Developing Guidance for Donor Intervention Randomized Controlled Trials: Initial Discussions From the Canada-United Kingdom 2022 Workshop
Authors: Slessarev Marat , Bain Katie L. , Basmaji John , Blydt-Hansen Tom D. , Cooper Jessie , D’Aragon Frédérick , Del Sorbo Lorenzo , Evans Amy , Gordon Anthony C. , Klein Gail , Meade Maureen O. , Murphy Nicholas , Thomas Helen L. , Weiss Matthew J. , Weijer Charles , Harvey Dan
Published: March 2024

Background.

Donor interventions, including medications, protocols, and medical devices administered to donors, can enhance transplantable organ quality and quantity and maximize transplantation success. However, there is paucity of high-quality evidence about their effectiveness, in part because of ethical, practical, and regulatory challenges, and lack of guidance about conduct of donor intervention randomized controlled trials (RCTs).

Methods.

With the vision to develop authoritative guidance for conduct of donor intervention RCTs, we convened a workshop of Canadian-United Kingdom experts in organ donation and transplantation ethics, research, and policy to identify stakeholders, explore unique challenges, and develop research agenda to inform future work in this promising field.

Results.

Donor intervention trials should consider perspectives of broad group of stakeholders including donors, transplant recipients, and their families; researchers in donation and transplantation; research ethics boards; and healthcare providers and administrators involved in donation and transplantation. Unique challenges include (1) research ethics (living versus deceased status of the donor at the time of intervention, intervention versus outcomes assessment in different individuals, harm-benefit analysis in donors versus recipients, consent, and impact on research bystanders); (2) outcome data standardization and linkage; and (3) regulatory and governance considerations.

Conclusions.

Donor intervention RCTs hold potential to benefit organ transplantation outcomes but face unique research ethics, outcome data, and regulatory challenges. By developing research agenda to address these challenges, our workshop was an important first step toward developing Canada-United Kingdom guidance for donor intervention RCTs that are poised to improve the quality and availability of transplantable organs.
Identification of Genetic Predisposition to Sjögren’s Syndrome by Whole Exome Sequencing
Authors: Guo Qiwei , Li Qiaowei , Lu Huiqin , Shi Yingying , Guo Jintao , Wang Hao , Deng Qiuxiao , Li Yihang , Liu Yuan , Shi Guixiu , Chen Shiju
Published: March 2024

A comprehensive understanding of the genetic predisposition associated with the initiation and development of Sjögren’s syndrome (SjS) is imperative. This would not only enrich our knowledge of the pathogenesis underlying this autoimmune disease but also address the long-standing clinical challenges of more timely diagnosis and effective treatment to retain organ function and improve prognosis. In this study, we used whole exome sequencing analysis of 50 patients with SjS to investigate the predisposing variants, genes, and their associated biological functions. Hundreds of predisposing genes were identified, and numerous biological processes and pathways were highlighted; suggesting a heterogeneity of genetic predisposition to SjS. Female patients carrying a greater number of enriched variants tended to have higher levels of serum IgG and corresponding systemic involvement, demonstrating the pivotal role of genetic predisposition in the pathogenesis of SjS. Biological function analysis indicated that a subset of SjS and neuropathies may share a similar genetic predisposition. Our results showed that extracellular matrix-receptor interactions, macrophage-associated biological functions, and motor proteins may play important roles in the pathogenesis of SjS, and macrophage-associated biological functions may be associated with early onset SjS in female patients. Furthermore, the identification of highly enriched variants in the patient cohort provides the possibility of advancing the diagnosis of SjS. In conclusion, our study provides an extensive framework for analysis of the genetic predisposition to SjS which can facilitate further focused and in-depth investigation of the pathogenetic mechanisms of specific genes, biological processes, and pathways; thereby contributing to the pathophysiology, diagnosis, and therapeutics of SjS.
Ischemia promotes hypertrophic nerve trunk formation and enteric neuron cell death in Hirschsprung’s disease
Authors: Xu Deshu , Liang Weiwei , Lan Chaoting , Li Lanying , Zhong Weiyong , Yao Meng , Zuo Xiaoyu , Zeng Jixiao , Zhong Wei , Wu Qiang , Lew Andrew M , Zhou Wenhao , Xia Huimin , Bai Fan , Zhang Yuxia , Zhang Yan
Published: March 2024

Objective

Enteric nervous system dysfunction is linked to digestive and neurological disorders. Hirschsprung’s disease (HSCR) is characterized by the loss of enteric neuron cells (ENCs) in the distal colon. Embryonic enteric neural crest cell (ENCC) migration defects contribute to HSCR development in some infants, but postnatal factors that regulate ENC fate are undetermined. We sought to establish how postnatal changes contribute to HSCR by profiling the colonic microenvironment of HSCR infants.

Design

In this study, we recruited infants with HSCR, infants with anorectal malformations but normal ENC development (CT), and a group of age-matched healthy control subjects. Laboratory findings and clinical manifestations were recorded. Single-cell and spatial transcriptome sequencing were applied to colonic tissues from a sub-cohort of CT and HSCR infants. Patient specimens, a mouse model of neonatal ischemic enterocolitis, andSox10knockdown mouse (Sox10WT/MUT) were used to reveal the factors that lead to ENC loss in HSCR infants.

Results

We discover that intestinal ischemia promotes CLDN1+hypertrophic nerve trunk formation and ENC death. Mechanistically, ischemia leads to defective nitric oxide (NO) signaling in ENCs, which aggravates mitochondria damage and caspase-mediated apoptosis that can be ameliorated by a NO donor drug.

Conclusion

We show that ischemia contributes to postnatal ENC loss in HSCR infants and suggest that NO donor drugs may alleviate ischemia-related ENC death.
Randomized Controlled Comparative Effectiveness Trial of Risk Model-Guided Clinical Decision Support for Suicide Screening
Authors: Walsh Colin G. , Ripperger Michael A. , Novak Laurie , Reale Carrie , Anders Shilo , Spann Ashley , Kolli Jhansi , Robinson Katelyn , Chen Qingxia , Isaacs David , Acosta Lealani Mae Y. , Phibbs Fenna , Fielstein Elliot , Wilimitis Drew , Musacchio Schafer Katherine , Hilton Rachel , Albert Dan , Shelton Jill , Stroh Jessica , Stead William W. , Johnson Kevin B.
Published: March 2024

Suicide prevention requires risk identification, appropriate intervention, and follow-up. Traditional risk identification relies on patient self-reporting, support network reporting, or face-to-face screening with validated instruments or history and physical exam. In the last decade, statistical risk models have been studied and more recently deployed to augment clinical judgment. Models have generally been found to be low precision or problematic at scale due to low incidence. Few have been tested in clinical practice, and none have been tested in clinical trials to our knowledge.

Methods

We report the results of a pragmatic randomized controlled trial (RCT) in three outpatient adult Neurology clinic settings. This two-arm trial compared the effectiveness of Interruptive and Non-Interruptive Clinical Decision Support (CDS) to prompt further screening of suicidal ideation for those predicted to be high risk using a real-time, validated statistical risk model of suicide attempt risk, with the decision to screen as the primary end point. Secondary outcomes included rates of suicidal ideation and attempts in both arms. Manual chart review of every trial encounter was used to determine if suicide risk assessment was subsequently documented.

Results

From August 16, 2022, through February 16, 2023, our study randomized 596 patient encounters across 561 patients for providers to receive either Interruptive or Non-Interruptive CDS in a 1:1 ratio. Adjusting for provider cluster effects, Interruptive CDS led to significantly higher numbers of decisions to screen (42%=121/289 encounters) compared to Non-Interruptive CDS (4%=12/307) (odds ratio=17.7, p-value <0.001). Secondarily, no documented episodes of suicidal ideation or attempts occurred in either arm. While the proportion of documented assessments among those noting the decision to screen was higher for providers in the Non-Interruptive arm (92%=11/12) than in the Interruptive arm (52%=63/121), the interruptive CDS was associated with more frequent documentation of suicide risk assessment (63/289 encounters compared to 11/307, p-value<0.001).

Conclusions

In this pragmatic RCT of real-time predictive CDS to guide suicide risk assessment, Interruptive CDS led to higher numbers of decisions to screen and documented suicide risk assessments. Well-powered large-scale trials randomizing this type of CDS compared to standard of care are indicated to measure effectiveness in reducing suicidal self-harm.

ClinicalTrials.govIdentifier:NCT05312437
Atomically accurate de novo design of antibodies with RFdiffusion
Authors: Bennett Nathaniel R. , Watson Joseph L. , Ragotte Robert J. , Borst Andrew J. , See DeJenae L. , Weidle Connor , Biswas Riti , Yu Yutong , Shrock Ellen L. , Ault Russell , Leung Philip J. Y. , Huang Buwei , Goreshnik Inna , Tam John , Carr Kenneth D. , Singer Benedikt , Criswell Cameron , Wicky Basile I. M. , Vafeados Dionne , Garcia Sanchez Mariana , Kim Ho Min , Vazquez Torres Susana , Chan Sidney , Sun Shirley M. , Spear Timothy , Sun Yi , OReilly Keelan , Maris John M. , Sgourakis Nikolaos G. , Melnyk Roman A. , Liu Chang C. , Baker David
Published: March 2024

Despite the central role that antibodies play in modern medicine, there is currently no method to design novel antibodies that bind a specific epitope entirely in silico. Instead, antibody discovery currently relies on animal immunization or random library screening approaches. Here, we demonstrate that combining computational protein design using a fine-tuned RFdiffusion network alongside yeast display screening enables the generation of antibody variable heavy chains (VHHs) and single chain variable fragments (scFvs) that bind user-specified epitopes with atomic-level precision. To verify this, we experimentally characterized VHH binders to four disease-relevant epitopes using multiple orthogonal biophysical methods, including cryo-EM, which confirmed the proper Ig fold and binding pose of designed VHHs targeting influenza hemagglutinin and Clostridium difficile toxin B (TcdB). For the influenza-targeting VHH, high-resolution structural data further confirmed the accuracy of CDR loop conformations. While initial computational designs exhibit modest affinity, affinity maturation using OrthoRep enables production of single-digit nanomolar binders that maintain the intended epitope selectivity. We further demonstrate the de novo design of single-chain variable fragments (scFvs), creating binders to TcdB and a Phox2b peptide-MHC complex by combining designed heavy and light chain CDRs. Cryo-EM structural data confirmed the proper Ig fold and binding pose for two distinct TcdB scFvs, with high-resolution data for one design additionally verifying the atomically accurate conformations of all six CDR loops. Our approach establishes a framework for the rational computational design, screening, isolation, and characterization of fully de novo antibodies with atomic-level precision in both structure and epitope targeting.
Identification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities
Authors: Loesch Douglas P. , Garg Manik , Matelska Dorota , Vitsios Dimitrios , Jiang Xiao , Ritchie Scott C. , Sun Benjamin B. , Runz Heiko , Whelan Christopher D. , Holman Rury R. , Mentz Robert J. , Moura Filipe A. , Wiviott Stephen D. , Sabatine Marc S. , Udler Miriam S. , Gause-Nilsson Ingrid A. , Petrovski Slavé , Oscarsson Jan , Nag Abhishek , Paul Dirk S. , Inouye Michael
Published: March 2024

Introduction

Type 2 diabetes (T2D) is a heterogeneous disorder for which disease-causing pathways are incompletely understood. Here, we mapped genetic risk for T2D and its comorbidities to proteins, mechanistic pathways and clinical outcomes using proteogenomic data from a population-scale biobank and two randomized controlled trials.

Methods

We tested polygenic scores (PGS) for T2D and its cardiometabolic comorbidities, plus five partitioned T2D PGS (beta cell, lipodystrophy, liver lipid, obesity, and liver lipid), for association with 2,922 circulating proteins in 54,306 multi-ancestry participants (of which 42,452 were unrelated and without prevalent cardiometabolic disease) from the UK Biobank (UKB). Then, we tested the PGS-associated proteins for association with incident cardiometabolic complications in two cardiovascular outcome trials among T2D patients with proteogenomic data: EXSCEL (N=2,823) and DECLARE-TIMI 58 (N=915). We assessed causality using two-sample Mendelian randomization and mediation.

Results

We identified 839 unique proteins significantly associated with any T2D PGS and 1,005 proteins that were associated with at least one cardiometabolic PGS. Some PGS-associated proteins such as TFF3, EFEMP1, and MMP12 were in turn associated with renal and cardiovascular trial outcomes. PGS association patterns revealed shared pathways, e.g., complement cascade, cholesterol metabolism, IGF signaling. The proteins underlying these pathways, such as LPA, C1S, and IGFBP2, were consistently associated with clinical trial outcomes or identified via causal inference.

Conclusions

This proteogenomic study revealed proteins and mechanistic pathways underlying T2D and related comorbidities, advancing our understanding of T2D pathobiology and identifying putative biomarkers. All our results are available in an online data portal (https://public.cgr.astrazeneca.com/t2d-pgs/v1/).
The link between theANPEPgene and type 2 diabetes mellitus may be mediated by the disruption of glutathione metabolism and redox homeostasis
Authors: Korvyakova Yaroslava , Azarova Iuliia , Klyosova Elena , Postnikova Maria , Makarenko Victor , Bushueva Olga , Solodilova Maria , Polonikov Alexey
Published: March 2024

Aminopeptidase N (ANPEP), a membrane-associated ectoenzyme, has been identified as a susceptibility gene for type 2 diabetes (T2D) by genome-wide association and transcriptome studies; however, the mechanisms by which this gene contributes to disease pathogenesis remain unclear. The aim of this study was to determine the comprehensive contribution of ANPEP polymorphisms to T2D risk and annotate the underlying mechanisms. A total of 3206 unrelated individuals including 1579 T2D patients and 1627 controls were recruited for the study. Twenty-three common functional single nucleotide polymorphisms (SNP) of ANPEP were genotyped by the MassArray-4 system. Six polymorphisms, rs11073891, rs12898828, rs12148357, rs9920421, rs7111, and rs25653, were found to be associated with type 2 diabetes for the first time (Pperm≤0.05). Common haplotype rs9920421G-rs4932143G-rs7111T was strongly associated with increased risk of T2D (Pperm=5.9×10-12), whereas two rare haplotypes such as rs9920421G-rs4932143C-rs7111T (Pperm=6.5×10-40) and rs12442778A-rs12898828A-rs6496608T-rs11073891C (Pperm=1.0×10-7) possessed strong protection against disease. We identified 38 and 109 diplotypes associated with T2D risk in males and females, respectively (FDR≤0.05). ANPEP polymorphisms showed associations with plasma levels of fasting blood glucose, aspartate aminotransferase, total protein and glutathione (P<0.05), and several haplotypes were strongly associated with the levels of reactive oxygen species and uric acid (P<0.0001). A deep literature analysis has facilitated the formulation of a hypothesis proposing that increased plasma levels of ANPEP as well as liver enzymes such as aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase serve as an adaptive response directed towards the restoration of glutathione deficiency in diabetics by stimulating the production of amino acid precursors for glutathione biosynthesis.

Highlights

Polymorphisms, rs11073891, rs12898828, rs12148357, rs9920421, rs7111, and rs25653 ofANPEP, were discovered as novel susceptibility markers for type 2 diabetes mellitus.

ne common and two rare haplotypes ofANPEPare strongly associated with increased and decreased risk of type 2 diabetes, respectively.

Thirty eight and one hundred and nineANPEPdiplotypes influenced disease risk in males and females, respectively.

Polymorphisms ofANPEPwere associated with plasma levels of fasting blood glucose, aspartate aminotransferase, total protein, glutathione, reactive oxygen species and uric acid in diabetics.

Increased plasma levels of ANPEP and liver enzymes (AST, ALT, and GGT) in T2D patients may reflect an adaptive response to glutathione deficiency through the formation of more amino acid precursors of glutathione.
Intra-species quantification reveals differences in activity and sleep levels in the yellow fever mosquito,Aedes aegypti
Authors: Ajayi Oluwaseun M. , Susanto Emily E. , Wang Lyn , Kennedy Jasmine , Ledezma Arturo , Harris Angeli’c , Smith Evan S. , Chakraborty Souvik , Wynne Nicole E. , Sylla Massamba , Akorli Jewelna , Otoo Sampson , Rose Noah H. , Vinauger Clément , Benoit Joshua B.
Published: March 2024

Aedes aegyptiis an important mosquito vector of human disease with a wide distribution across the globe. Climatic conditions and ecological pressure drive differences in the biology of several populations of this mosquito, including blood-feeding behavior and vector competence. However, no study has compared activity and/or sleep among different populations/lineages ofAe. aegypti. Having recently established sleep-like states in three mosquito species with observable differences in timing and amount of sleep among species, we investigated differences in activity and sleep levels among 17Ae. aegyptilines drawn from both its native range in Africa and its invasive range across the global tropics. Activity monitoring indicates that all the lines show consistent diurnal activity, but significant differences in activity level, sleep amount, number of sleep bouts, and bout duration were observed among the lines. Variations in specific activity and sleep parameters were explained by differences in host preference, ancestry, and human population density for the lineages collected in Africa. This study provides evidence that the diurnal sleep and activity profiles forAe. aegyptiare consistent, but there are significant population differences forAe. aegyptisleep and activity levels and interactions with humans may significantly impact mosquito activity and sleep.
PH-SENSITIVE NANODROPLETS FOR CONTROLLED DELIVERY OF BERBERINE CHLORIDE
Authors: Hao Shengjie , Wang Shiyu , Cao Jiaqi , Xue Zhiyuan , Luo Zeyu , Wu Peirun , Chen Guilin
Published: March 2024

Background

The development of nanocarriers with precise control over drug release is crucial for targeted therapy. This study focuses on the design and optimization of pH-sensitive gelatin/perfluorohexane (PFH) nanodroplets loaded with berberine chloride, a model drug relevant to traditional Chinese medicine.

Subjects and Methods

Nanodroplets were prepared using an emulsion technique, with optimization of parameters including homogenization rate, polymer concentration, surfactant, drug, and perfluorocarbon conte nt.

Results

The optimized formulation resulted in nanodroplets with a mean particle size of 281.7 nm and a drug encapsulation efficiency of 66.8 ± 1.7%. Characterization studies confirmed successful encapsulation and pH-responsive behavior. Ultrasound stimulation significantly enhanced drug release, with 150 kHz frequency proving more effective than 1 MHz. Stability studies demonstrated prolonged stability over one month at 4°C. Following 10 minutes of ultrasound irradiation, the nanodroplets exhibited 89.4% cumulative drug release.

Conclusions

In conclusion, these pH-sensitive nanodroplets show potential for delivering berberine chloride in a controlled manner, connecting traditional Chinese medicine with contemporary drug delivery methods.
Design principles for accurate folding of DNA origami
Authors: Aksel Tural , Navarro Erik J. , Fong Nicholas , Douglas Shawn M.
Published: March 2024

We describe design principles for accurate folding of three-dimensional DNA origami. To evaluate design rules, we reduced the problem of DNA strand routing to the known problem of shortest-path finding in a weighted graph. To score candidate DNA strand routes we used a thermodynamic model that accounts for enthalpic and entropic contributions of initial binding, hybridization, and DNA loop closure. We encoded and analyzed new and previously reported design heuristics. Using design principles emerging from this analysis, we redesigned and fabricated multiple shapes and compared their folding accuracy using electrophoretic mobility analysis and electron microscopy imaging. We demonstrate accurate folding can be achieved by optimizing staple routes using our model, and provide a computational framework for applying our methodology to any design.
Development of covalent probes to captureLegionella pneumophilaeffector enzymes
Authors: Kloet Max S. , Mukhopadhyay Rishov , Mukherjee Rukmini , Misra Mohit , Jeong Minwoo , Talavera Ormeño Cami M. P. , Moutsiopoulou Angeliki , Tjokrodirijo Rayman T. N. , van Veelen Peter A. , Shin Donghyuk , Ðikić Ivan , Sapmaz Aysegul , Kim Robbert Q. , van der Heden van Noort Gerbrand J.
Published: March 2024

Upon infection of host cells,Legionella pneumophilareleases a multitude of effector enzymes into the cells cytoplasm that hijack a plethora of cellular activities, including the hosts ubiquitination pathways. Effectors belonging to the SidE-family are involved in non-canonical serine phosphoribosyl ubiquitination of host substrate proteins contributing to the formation of a Legionella-containing vacuole that is crucial in the onset of Legionnaires’ disease. This dynamic process is reversed by effectors called Dups that hydrolyse the phosphodiester in the phosphoribosyl ubiquitinated protein. We installed reactive warheads on chemically prepared ribosylated ubiquitin to generate a set of probes targeting these Legionella enzymes. In vitro tests on recombinant DupA revealed that a vinyl sulfonate warhead was most efficient in covalent complex formation. Mutagenesis and x-ray crystallography approaches were used to identify the site of covalent crosslinking to be an allosteric cysteine residue. The subsequent application of this probe highlights the potential to selectively enrich the Dup enzymes from Legionella-infected cell lysates.
RFW captures species-level full profile of metagenomic functions via integrating genome annotation information
Authors: Mi Kai , Liu Xingyin
Published: March 2024

Functional profiling on whole-metagenome shotgun sequencing (WMS) has made great contribution to the development of our understanding in microbe-host interactions. In this work, we revealed that severe microbial functional information loss of current functional profiling methods existed at both taxon-level and community-level. To correct the distortion brought by information incompleteness, we developed a new framework, RFW (Reference based functional profile inference on WMS), to infer microbial functional abundance on WMS through utilizing information from genome function annotation and WMS taxonomic profile. Furthermore, we built up a new algorithm for absolute abundance change quantification of microbial function between groups under RFW framework. By applying RFW to several datasets related to autism spectrum disorder and colorectal cancer, we revealed that RFW greatly renewed our knowledge in downstream analysis, including differential microbial function identification, association analysis between microbial function and host phenotype, etc. RFW are open-source and freely available athttps://github.com/Xingyinliu-Lab/RFW.
Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels
Authors: Eiken Madeline K. , Childs Charlie J. , Brastrom Lindy K. , Frum Tristan , Plaster Eleanor M. , Shachaf Orren , Pfeiffer Suzanne , Levine Justin E. , Alysandratos Konstantinos-Dionysios , Kotton Darrell N. , Spence Jason R. , Loebel Claudia
Published: March 2024

Highlights

Alveolar organoids are formed with a two-step, Matrigel-free method in a semi-synthetic hyaluronic acid (HA) hydrogel

The two-step method offers control over alveolar size, density, and growth

Alveolar organoids maintain their AT2 identity in HA hydrogels

Alveolar organoids secrete nascent extracellular matrix supporting organoid growth without Matrigel

Human induced pluripotent stem cell (iPSC) derived alveolar organoids have emerged as a system to model the alveolar epithelium in homeostasis and disease. However, alveolar organoids are typically grown in Matrigel, a mouse-sarcoma derived basement membrane matrix that offers poor control over matrix properties, prompting the development of synthetic hydrogels as a Matrigel alternative. Here, we develop a two-step culture method that involves pre-aggregation of organoids in hydrogel-based microwells followed by embedding in a synthetic hydrogel that supports alveolar organoid growth, while also offering considerable control over organoid and hydrogel properties. We find that the aggregated organoids secrete their own nascent extracellular matrix (ECM) both in the microwells and upon embedding in the synthetic hydrogels. Thus, the synthetic gels described here allow us to de-couple exogenous and nascent ECM in order to interrogate the role of ECM in organoid formation.
Analytical analysis of the generation of a rotating driving magnetic field on the outer surface of a magnetic pinch load with a helical return current post
Authors: Duan Shu-Chao , He Ge-Guang , Zhou Shao-Tong , Kan Ming-Xian , Wang Gang-Hua
Published: March 2024

A recently emerging approach adopts a directionally time-varying (rotating) magnetic field to drive a pinch load, aiming to mitigate the inherent magneto-Rayleigh-Taylor instability in dynamic Z pinches. A helical return current post (RCP) serves as a functional structural element capable of generating the requisite driving magnetic field for this purpose in the load region. This paper first calculates the current azimuthally induced on the outer surface of a magnetically pinched load within this type of RCP using a zero-dimensional lumped-parameter circuit model. The results show that the induced current deviates significantly from the presumed “perfect” induced current (100% amplitude) as reported in the literature [S. A. Sorokin, ); P. F. Schmit , ); G. A. Shipley , ); and P. C. Campbell , ], with an effective coefficient of current induction considerably less than 1. However, even when the load is fully compressed to the axis, the effective coefficient does not approach zero but rather converges to a finite value that solely depends on the aspect ratio of the RCP. This is quite favorable for the suppression of magneto-Rayleigh-Taylor instability in the Z pinch. As for the pointlike X pinch, the axial magnetic field does not tend to zero but a finite value, though the effective coefficient tends to zero, and this result may be used to suppress the instability in X pinch and improve the time stability and spatiotemporal unity of hot spots. In addition, the anode and cathode plates have the potential to enhance the current induced in the load. This paper then analyzes the axial distribution and time behavior of the induced current adopting an approximate analytical method and numerical integration and finds an approximate invariance that can be well characterized by δt, the product of the normalized skin depth and time. Similar values of δt indicate similar axial distribution characteristics. When δt is lower than, at, or higher than the critical region (∼0.1–0.3), the axial distribution appears dumbbell shaped, nearly flat, and arched, respectively. These distributively induced currents can be exploited to achieve quasispherical, near flat, and dumbbell-shaped implosions, respectively.

Published by the American Physical Society
2024
Accelerating the convergence of free electron laser simulations by retrieving a spatially coherent component of microbunching
Authors: Tanaka Takashi
Published: March 2024

A simple method to reduce the numerical cost in free electron laser (FEL) simulations is presented, which is based on retrieving a spatially coherent component of microbunching to suppress artifact effects that can potentially overestimate the FEL gain; this significantly reduces the number of macroparticle to reach the numerical convergence and enables the computation of amplified radiation with semianalytical formulas. Examples of FEL simulations performed to demonstrate the proposed method show that the computation time to get a reliable result is reduced by 1–2 orders of magnitude depending on the simulation condition.

Published by the American Physical Society
2024
Near-wall depletion and layering affect contact line friction of multicomponent liquids
Authors: Pellegrino Michele , Hess Berk
Published: March 2024

The main causes of energy dissipation in micro- and nanoscale wetting are viscosity and liquid-solid friction localized in the three-phase contact line region. Theoretical models predict the contact line friction coefficient to correlate with the shear viscosity of the wetting fluid. Experiments conducted to investigate such correlation have not singled out a unique scaling law between the two coefficients. We perform molecular dynamics simulations of liquid water-glycerol droplets wetting silicalike surfaces, aimed to demystify the effect of viscosity on contact line friction. The viscosity of the fluid is tuned by changing the relative mass fraction of glycerol in the mixture and it is estimated both via equilibrium and nonequilibrium molecular dynamics simulations. Contact line friction is measured directly by inspecting the velocity of the moving contact line and the microscopic contact angle. It is found that the scaling between contact line friction and viscosity is sublinear, contrary to the prediction of molecular kinetic theory. The disagreement is explained by accounting for the depletion of glycerol in the near-wall region. A correction is proposed, based on multicomponent molecular kinetic theory and the definition of a rescaled interfacial friction coefficient.

Published by the American Physical Society
2024
First Measurement Using Elliptically Polarized Photons of the Double-Polarization Observable
E
for
γp→pπ0
and
γp→nπ+
Authors: Afzal F. , Spieker K. , Hurck P. , Abt S. , Achenbach P. , Adlarson P. , Ahmed Z. , Akondi C. S. , Annand J. R. M. , Arends H. J. , Bashkanov M. , Beck R. , Biroth M. , Borisov N. , Braghieri A. , Briscoe W. J. , Cividini F. , Collicott C. , Costanza S. , Denig A. , Dieterle M. , Downie E. J. , Drexler P. , Fegan S. , Gardner S. , Ghosal D. , Glazier D. I. , Gorodnov I. , Gradl W. , Gurevich D. , Heijkenskjöld L. , Hornidge D. , Huber G. M. , Kashevarov V. L. , Kay S. J. D. , Korolija M. , Krusche B. , Lazarev A. , Livingston K. , Lutterer S. , MacGregor I. J. D. , Macrae R. G. , Manley D. M. , Martel P. P. , Miskimen R. , Mocanu M. , Mornacchi E. , Mullen C. , Neganov A. , Neiser A. , Oberle M. , Ostrick M. , Otte P. B. , Paudyal D. , Pedroni P. , Powell A. , Reicherz G. , Rostomyan T. , Sfienti C. , Sokhoyan V. , Steffen O. , Strakovsky I. I. , Strub T. , Supek I. , Thiel A. , Thiel M. , Thomas A. , Usov Yu. A. , Wagner S. , Walford N. K. , Watts D. P. , Werthmüller D. , Wettig J. , Witthauer L. , Wolfes M. , Zachariou N. ,   A2 Collaboration at MAMI
Published: March 2024

We report the measurement of the helicity asymmetry E for the pπ0 and nπ+ final states using, for the first time, an elliptically polarized photon beam in combination with a longitudinally polarized target at the Crystal Ball experiment at MAMI. The results agree very well with data that were taken with a circularly polarized photon beam, showing that it is possible to simultaneously measure polarization observables that require linearly (e.g., G) and circularly polarized photons (e.g., E) and a longitudinally polarized target. The new data cover a photon energy range 270–1400 MeV for the pπ0 final state (230–842 MeV for the nπ+ final state) and the full range of pion polar angles, θ, providing the most precise measurement of the observable E. A moment analysis gives a clear observation of the pη cusp in the pπ0 final state.

Published by the American Physical Society
2024
Crystal structure, intermolecular interactions, charge–density distribution and ADME properties of the acridinium 4-nitrobenzoate and 2-amino-3-methylpyridinium 4-nitrobenzoate salts: a combined experimental and theoretical study
Authors: Balasubramanian Hemalatha , Mariappan Petchi Raman , Poomani Kumaradhas
Published: March 2024

Acridines are a class of bioactive agents which exhibit high biological stability and the ability to intercalate with DNA; they have a wide range of applications. Pyridine derivatives have a wide range of biological activities. To enhance the properties of acridine and 2-amino-3-methylpyridine as the active pharmaceutical ingredient (API), 4-nitrobenzoic acid was chosen as a coformer. In the present study, a mixture of acridine and 4-nitrobenzoic acid forms the salt acridinium 4-nitrobenzoate, C13H10N+·C7H4NO4
− (I), whereas a mixture of 2-amino-3-methylpyridine and 4-nitrobenzoic acid forms the salt 2-amino-3-methylpyridinium 4-nitrobenzoate, C6H9N2
+·C7H4NO4
− (II). In both salts, protonation takes place at the ring N atom. The crystal structure of both salts is predominantly governed by hydrogen-bond interactions. In salt I, C—H...O and N—H...O interactions form an infinite chain in the crystal, whereas in salt II, intermolecular N—H...O interactions form an eight-membered R
2
2(8) ring motif. A theoretical charge–density analysis reveals the charge–density distribution of the inter- and intramolecular interactions of both salts. An in-silico ADME analysis predicts the druglikeness properties of both salts and the results confirm that both salts are potential drug candidates with good bioavailability scores and there is no violation of the Lipinski rules, which supports the druglikeness properties of both salts. However, although both salts exhibit drug-like properties, salt I has higher gastrointestinal absorption than salt II and hence it may be considered a potential drug candidate.
trans-Dibromidotetrakis(5-methyl-1H-pyrazole-κN
2)manganese(II)
Authors: Athan Manikumar , Krishnan Soundararajan , Loganathan Nagarajan
Published: March 2024

The title compound, trans-dibromidotetrakis(5-methyl-1H-pyrazole-κN
2)manganese(II), [MnBr2(C4H6N2)4] or [Mn(3-MePzH)4Br2] (1) crystallizes in the triclinic P\overline{1} space group with the cell parameters a = 7.6288 (3), b = 8.7530 (4), c = 9.3794 (4) Å and α = 90.707 (4), β = 106.138 (4), γ = 114.285 (5)°, V = 542.62 (5) Å3, T = 120 K. The asymmetric unit contains only half the molecule with the manganese atom is situated on a crystallographic inversion center. The 3-MePzH ligands are present in an AABB type manner with two methyl groups pointing up and the other two down. The supramolecular architecture is characterized by several intermolecular C—H...N, N—H...Br, and C—H...π interactions. Earlier, a polymorphic structure of [Mn(3-MePzH)4Br2] (2) with a similar geometry and also an AABB arrangement for the pyrazole ligands was described [Reedijk et al. (1971). Inorg. Chem. 10, 2594–2599; a = 8.802 (6), b = 9.695 (5), c = 7.613 (8) Å and α = 105.12 (4), β = 114.98 (4), γ = 92.90 (3)°, V = 558.826 (5) Å3, T = 295 K]. A varying supramolecular pattern was reported, with the structure of 1 featuring a herringbone type pattern while that of structure 2 shows a pillared network type of arrangement along the a axis. A nickel complex [Ni(3-MePzH)4Br2] isomorphic to 1 and the analogous chloro derivatives of FeII, CoII and CuII are also known.
Risk Management practices and potential fraudulent financial reporting: evidence from Malaysia
Authors: Madah Marzuki Marziana , Nik Abdul Majid Wan Zurina , Abu Bakar Hatinah , Abdul Wahab Effiezal Aswadi , Mohd Sanusi Zuraidah
Published: March 2024

Purpose

This paper investigates the relationship between risk management practices and potential fraudulent financial reporting in Malaysia by considering recent regulatory reforms of the Malaysian government on risk management practices.

Design/methodology/approach

The sample of this study was based on 257 firm-year observations during the 2012–2017 period. This study employed panel-least square regressions with period fixed effects.

Findings

This study found a significant association between risk management activities in the disclosure and potential fraudulent financial reporting. Nevertheless, this study found there is insignificant effect of the risk-management committee in reducing potential of fraudulent financial reporting.

Originality/value

This study is a pioneer research that relates firms’ risk management practices with potential fraudulent financial reporting measured by F-score. Thus, this study provides an insight to regulators on the extent of risk-management practices in deterring potential fraudulent financial reporting which can be used as an input for greater enforcement of risk-management regulations.
Confidence intervals for functions of signal-to-noise ratio with application to economics and finance
Authors: Thangjai Warisa , Niwitpong Sa-Aat
Published: March 2024

Purpose

Confidence intervals play a crucial role in economics and finance, providing a credible range of values for an unknown parameter along with a corresponding level of certainty. Their applications encompass economic forecasting, market research, financial forecasting, econometric analysis, policy analysis, financial reporting, investment decision-making, credit risk assessment and consumer confidence surveys. Signal-to-noise ratio (SNR) finds applications in economics and finance across various domains such as economic forecasting, financial modeling, market analysis and risk assessment. A high SNR indicates a robust and dependable signal, simplifying the process of making well-informed decisions. On the other hand, a low SNR indicates a weak signal that could be obscured by noise, so decision-making procedures need to take this into serious consideration. This research focuses on the development of confidence intervals for functions derived from the SNR and explores their application in the fields of economics and finance.

Design/methodology/approach

The construction of the confidence intervals involved the application of various methodologies. For the SNR, confidence intervals were formed using the generalized confidence interval (GCI), large sample and Bayesian approaches. The difference between SNRs was estimated through the GCI, large sample, method of variance estimates recovery (MOVER), parametric bootstrap and Bayesian approaches. Additionally, confidence intervals for the common SNR were constructed using the GCI, adjusted MOVER, computational and Bayesian approaches. The performance of these confidence intervals was assessed using coverage probability and average length, evaluated through Monte Carlo simulation.

Findings

The GCI approach demonstrated superior performance over other approaches in terms of both coverage probability and average length for the SNR and the difference between SNRs. Hence, employing the GCI approach is advised for constructing confidence intervals for these parameters. As for the common SNR, the Bayesian approach exhibited the shortest average length. Consequently, the Bayesian approach is recommended for constructing confidence intervals for the common SNR.

Originality/value

This research presents confidence intervals for functions of the SNR to assess SNR estimation in the fields of economics and finance.
A meta-analytical study of cultural conditions moderating the relationship between environmental performance and environmental disclosure
Authors: Ali Waris , Wilson Jeffery , Saeed Taiba
Published: March 2024

Purpose

This study aims to examine the moderating effect of cultural conditions on the relationship between environmental performance and environmental disclosure.

Design/methodology/approach

The authors used meta-analysis technique to examine 100 effect sizes from 43 studies published between 1982 and 2023 to integrate the existing results and to detect causes contributing to variability of results across studies.

Findings

There is a significant positive relationship between environmental performance and environmental disclosure. Further, the authors found that cultures with long-term orientation positively moderated the relationship, whereas cultures with high uncertainty avoidance and indulgence negatively moderated it.

Research limitations/implications

This study did not account for the problem of endogeneity between environmental performance and environmental disclosure because most of the already published studies included in the authors’ meta-analysis did not address this issue.

Practical implications

This research provides regulators and policymakers insights on the influence of cultural factors on environmental disclosure and performance, critical information to consider when adopting, or revising social and environmental policy and regulations within a country.

Originality/value

To the best of the authors’ knowledge, this is the first meta-analysis study examining different cultural dimensions influencing the relationship between environmental performance and environmental disclosure and contributes new knowledge to the literature on determinants of environmental disclosure.
Alpha Design Technologies: making a mark in India’s Defence exports
Authors: Arjunan Satyanandini , Zachariah Minu , Bhat Prathima K.
Published: March 2024

Learning outcomes

Alpha Design Technologies Private Limited (ADTL) was started in 2004 by Colonel H.S. Shankar after his retirement from services in the Indian Army and Bharat Electronics Limited (BEL). Aggressively growing the company from US$0.04m in 2004 to US$100m in 2022, he proved that age was not a barrier to success in entrepreneurship. His aspirations were to gain a greater presence in foreign markets through higher exports. After reading this case study, the students will be able to understand how the defence sector evolved in India and the role of private-sector enterprises; recognise the risks and opportunities in the changing dynamics of defence sector in India; believe that the ideas and capabilities of an entrepreneur increase with relevant previous experiences; appreciate the ambition and managerial capabilities of an entrepreneur even at the age of 60; apply Ajzen’s theory of planned behaviour on the entrepreneurial journey of Shankar and formulate strategies for growth.

Case overview/synopsis

Started in the year 2004, ADTL specialises in manufacturing defence-related products. ADTL was cofounded by Shankar, at the age of 60. His experience of working with the Indian Army and BEL in various capacities gave him the proficiency to start a venture on his own after his retirement. The ecosystem in India was favourable for ADTL as the Government opened up the defence sector for private players. Nevertheless, age was not a barrier for this senior citizen to tap the opportunity and work aggressively to grow his venture from US$0.04m in 2004 to US$100m in 2022. By 2023, ADTL had an employee strength of 1,200 including 650 engineers, and they emerged as a market leader in Software Defined Radio space. They manufactured around 200 different products for defence and space. ADTL exported 60% of the defence products to countries such as Israel, the USA and Germany. Moving forward, the dream for Shankar was to make a mark in the defence geography of the world through ADTL, by improving its export volumes and also through strategic alliances.

Complexity academic level

This case study can be taught to Master of Business Administration/postgraduate degree in management students as a part of the introductory course on entrepreneurship and strategy. This case study can be used specifically to make the students understand the role of private sector in the manufacturing of defence products after the liberalisation policy of the Government of India. The intention was not only to protect the nation from the threat posed by neighbouring countries but also to promote exports of defence products to other countries to improve foreign exchange earnings.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 3: Entrepreneurship.