bluuebunny/crossref_metadata_2025 huggingface dataset:
Low preoperative serum uric acid is associated with early acute kidney injury after living donor liver transplantation
Authors: Wu Yueh-Tse , Hu Li-Min , Lee Chao-Wei , Lee Wei-Chen , Lin Jr-Rung , Tsai Hsin-I , Yu Huang-Ping
Published: May 2024

Background:

Liver transplantation is treatment option for patients with end-stage liver disease and hepatocellular carcinoma. Renal function deterioration significantly impacts the survival rates of liver recipients, and serum uric acid (SUA) is associated with both acute and chronic renal function disorders. Thus, our study aimed to assess the relationship and predictive value of preoperative SUA level and postoperative acute kidney injury (AKI) in living donor liver transplantation (LDLT).

Methods:

We conducted a prospective observational study on 87 patients undergoing LDLT. Blood samples were collected immediately before LDLT, and renal function status was followed up for 3 consecutive days postoperatively.

Results:

Low SUA levels (cutoff value 4.15 mg/dL) were associated with a high risk of early posttransplantation AKI. The area under the curve was 0.73 (sensitivity, 79.2%; specificity, 59.4%). Although not statistically significant, there were no deaths in the non-AKI group but two in the early AKI group secondary to liver graft dysfunction in addition to early AKI within the first month after LDLT.

Conclusion:

AKI after liver transplantation may lead to a deterioration of patient status and increased mortality rates. We determined low preoperative SUA levels as a possible risk factor for early postoperative AKI.
Telemedicine for emergency patient rescue
Authors: Subramanian Sanjay , Pamplin Jeremy C.
Published: May 2024

Purpose of review

This article summarizes recent developments in the application of telemedicine, specifically tele-critical care (TCC), toward enhancing patient care during various types of emergencies and patient rescue scenarios when there are limited resources in terms of staff expertise (i.e., knowledge, skills, and abilities), staffing numbers, space, and supplies due to patient location (e.g., a non-ICU bed, the emergency department, a rural hospital) or patient volume as in pandemic surges.

Recent findings

The COVID-19 pandemic demonstrated the need for rapidly scalable and agile healthcare delivery systems. During the pandemic, clinicians and hospital systems adopted telemedicine for various applications. Taking advantage of technological improvements in cellular networks and personal mobile devices, and despite the limited outcomes literature to support its use, telemedicine was rapidly adopted to address the fundamental challenge of exposure in outpatient settings, emergency departments, patient follow-up, and home-based monitoring. A critical recognition was that the modality of care (e.g., remote vs. in-person) was less important than access to care, regardless of the patient outcomes. This fundamental shift, facilitated by policies that followed emergency declarations, provided an opportunity to maintain and, in many cases, expand and improve clinical practices and hospital systems by bringing expertise to the patient rather than the patient to the expertise. In addition to using telemedicine to maintain patient access to healthcare, TCC was harnessed to provide local clinicians, forced to manage critically ill patients beyond their normal scope of practice or experience, access to remote expertise (physician, nursing, respiratory therapist, pharmacist). These practices supported decades of literature from the telemedicine community describing the effectiveness of telemedicine in improving patient care and the many challenges defining its value.

In this review, we summarize numerous examples of innovative care delivery systems that have utilized telemedicine, focusing on ‘mobile’ TCC technology solutions to effectively deliver the best care to the patient regardless of patient location. We emphasize how a ‘paradigm of better’ can enhance the entirety of the healthcare system.
The Impact of Restricted Clinical Experiences During a Pandemic on Newly Graduated Nurses' Experiences
Authors: Nelson Kimberly , Weyant Donna , Bogue Kate Anderson , Parrotte Jennifer , Jeffery Carrie , George Elisabeth , George Robin , Tinelli Judith , Boulanger Kimberly , Luckenbaugh Kelly , Ziccardi Sarah , Zillman Jan , Henry Connie , Davis Amy Beth , Klinge Erin , McCreary Delores
Published: May 2024

A multihospital study examined the impact of restricted clinical opportunities during COVID-19 on newly graduated nurses' experiences, self-reported competence, and self-reported errors upon entry into a nurse residency program and at 6 months. Newly graduated nurses' experiences (n = 2,005) were described using comparative data from cohorts before and during restricted experiences across 22 hospitals; minimal differences were observed. Nursing professional development specialists can utilize this information when creating and sustaining transition-to-practice programs.
177Lu-FAP-2286 Therapy in a Patient With Metastatic Rhabdoid Meningioma
Authors: Wan Zibei , Wang Wei , Chen Yue , Zheng Wenlu , Huang Zhanwen
Published: May 2024

Rhabdoid meningioma is a rare subtype of meningioma and has a poor prognosis. Herein, we reported a patient of rhabdoid meningioma with multiple liver, pancreas, and bone metastases, who received 177Lu-FAP-2286 therapy. After 1 treatment cycle, 68Ga-FAP-2286 PET/CT revealed partial remission of the lesions.
Pediatric Plastic Surgery Under Local Anesthesia
Authors: LaGuardia Jonnby S. , Ali-Khan Safi , LaBarge Dalton , Morrison Clinton
Published: May 2024

Background

Increasing research has shown that select surgical procedures can be performed in an office-based environment with low complication rates. Within the field of plastic surgery, these findings have mainly been studied in adult populations. However, studies regarding the safety and efficacy of office-based plastic surgery in the pediatric population are lacking. In the present study, we demonstrate that appropriately selected office-based pediatric plastic surgery procedures can be performed under local anesthesia for a variety of common surgical indications with low complication rates.

Methods

A retrospective case series of pediatric plastic surgery patients who underwent in-office procedures under local anesthesia at a single academic institution from September 2014 to June 2020 was performed.

Results

Five hundred nine patients were treated in an office setting for various etiologies over the study period. A total of 48.9% of the patients were male and 51.1% were female. Patient age at time of procedure ranged from 24 days to 17 years of age with a median age of 13 years. A total of 778 lesions were treated. There were 10 total complications (1.29%) over the study period with only one surgical site infection that resolved with antibiotic treatment.

Conclusions

Our work indicates that select pediatric plastic surgery procedures can be performed under local anesthesia with low complication rates.
We Are Not Speaking the Same Language
Authors: Attalla Philopatir , Becker Miriam , Clark Robert Craig , Reid Chris M. , Brazio Philip S.
Published: May 2024

Introduction

Current Procedural Terminology (CPT) codes provide a uniform language for medical billing, but specific codes have not been assigned for lymphatic reconstruction techniques. The authors hypothesized that inadequate codes would contribute to heterogeneous coding practices and reimbursement challenges, ultimately limiting surgeons' ability to treat patients.

Methods

A 22-item virtual questionnaire was offered to 959 members of the American Society of Reconstructive Microsurgeons to assess the volume of lymphatic reconstruction procedures performed, CPT codes used for each procedure, and challenges related to coding and providing care.

Results

The survey was completed by 66 board-certified/board-eligible plastic surgeons (6.9%), who unanimously agreed that lymphatic surgery is integral to cancer care, with 86.4% indicating that immediate lymphatic reconstruction should be offered after lymphadenectomy. Most performed lymphovenous bypass, immediate lymphatic reconstruction, liposuction, and vascularized lymph node transfer.

Respondents reported that available CPT codes failed to reflect procedural scope. A wide variety of CPT codes was used to report each type of procedure. Insurance coverage problems led to 69.7% of respondents forgoing operations and 32% reducing treatment offerings. Insurance coverage and CPT codes were identified as significant barriers to care by 98.5% and 95.5% of respondents, respectively.

Conclusions

Respondents unanimously agreed on the importance of lymphatic reconstruction in cancer care, and most identified inadequate CPT codes as causing billing issues, which hindered their ability to offer surgical treatment. Appropriate and specific CPT codes are necessary to ensure accuracy and consistency of reporting and ultimately to improve patient access to care.
TAG-FREE GLYCOSYLATED RHMFG-E8 AS A THERAPY FOR ACUTE KIDNEY INJURY
Authors: Zhang Fangming , Ma Gaifeng , Chaung Wayne , Jacob Asha , Brenner Max , Wang Ping
Published: May 2024

Background: Acute kidney injury (AKI) can result from renal ischemia and reperfusion (I/R) and often occurs during surgical procedures in cardiac, liver, kidney transplantation, and trauma-hemorrhage. Milk fat globule epidermal growth factor-factor VIII (MFG-E8) functions as a bridging molecule to promote the removal of dying cells by professional phagocytes. Because MFG-E8 promotes clearance of apoptotic cells, we have explored its therapeutic potential in various organ injury conditions. To develop human MFG-E8 as a potential therapy, we have generated a human cell-expressed, and thus glycosylated, tag-free recombinant human (rh) MFG-E8 and tested its safety and biological activity in vitro. We hypothesize that the tag-free glycosylated rhMFG-E8 is protective in I/R-induced AKI and it can be developed as an effective therapy for AKI. Methods: To assess the pharmacokinetic properties of the tag-free rhMFG-E8, Sprague-Dawley rats were either untreated or treated with a bolus dose of the tag-free rhMFG-E8, blood collected at various time points and the recovery of human MFG-E8 in the blood were measured by ELISA. Adult male C57BL6 mice underwent bilateral renal ischemia for 30 min, and immediately upon reperfusion, mice were treated intraperitoneally with either normal saline (vehicle) or 20 μg/kg human cell expressed, glycosylated tag-free rhMFG-E8. At either 24 h or 48 h after I/R, blood and kidneys were harvested for further analysis. In separate cohorts of mice after I/R and treatment, mice were observed for 10 days, and survival recorded. Results: AKI rats treated with the tag-free rhMFG-E8 had similar half-life as those in the treated control rats. At 48 h after I/R-induced AKI, renal function markers, blood urea nitrogen, and creatinine were increased and treatment with the tag-free rhMFG-E8 significantly decreased these markers. At both 24 h and 48 h after AKI, inflammatory cytokines, TNF-α, IL-6, and IL-1β were increased and treatment decreased these levels. The kidney mRNA expressions of these cytokines were also increased at 24 h after AKI and treatment significantly decreased those mRNA expressions. Histologically, at 48 h after AKI, tubular damage, and the number of TUNEL staining cells were increased and treatment markedly decreased these measurements. Administration of tag-free rhMFG-E8 at the time of reperfusion improved survival in a 10-day survival study. Conclusion: Our new human cell-expressed tag-free rhMFG-E8 is protective in I/R-induced AKI and it may have the potential to be further developed as a safe and effective therapy for AKI.
Generalizability of foot placement control strategies during unperturbed and perturbed gait
Authors: Liu Chang , Valero-Cuevas Francisco J. , Finley James M.
Published: May 2024

Control of foot placement is an essential strategy for maintaining balance during walking. During unperturbed, steady-state walking, foot placement can be accurately described as a linear function of the body’s centre of mass (CoM) state at midstance. However, it is uncertain if this mapping from CoM state to foot placement generalizes to larger perturbations that could potentially cause falls. Recovery from these perturbations may require reactive control strategies not observed during unperturbed walking. Here, we used unpredictable changes in treadmill belt speed to assess the generalizability of foot placement mappings identified during unperturbed walking. We found that foot placement mappings generalized poorly from unperturbed to perturbed walking and differed for forward perturbation versus backward perturbation. We also used the singular value decomposition of the mapping matrix to reveal that people were more sensitive to backward versus forward perturbations. Together, these results indicate that a single linear mapping cannot describe the foot placement control during both forward and backward losses of balance induced by treadmill belt speed perturbations. Better characterization of human balance control strategies could improve our understanding of why different neuromotor disorders result in heightened fall risk and inform the design of controllers for balance-assisting devices.
Carbon capture and storage in low-carbon concrete using products derived from olivine
Authors: Shanks Barney , Howe Caitlin , Draper Sam , Wong Hong , Cheeseman Christopher
Published: May 2024

A novel process is reported that produces amorphous silica and nesquehonite (MgCO
3
·3H
2
O) from the magnesium silicate mineral olivine ((Mg, Fe)
2
·SiO
4
). The amorphous silica forms a supplementary cementitious material for use in concrete. The formation of nesquehonite sequesters carbon making the overall process carbon negative. Nesquehonite can also be used to form low-carbon construction products such as bricks, blocks and boards. This article reports on key process optimization studies. The potential for amorphous precipitated silica derived from olivine to produce carbon-negative concrete is discussed.
Computational and spectroscopic ‍characterization of thianthrene
Authors: Rushworth Rachel H. , Pascariu Matei , Sarter Mona , Parker Stewart F.
Published: May 2024

In this work, we have carried out a comprehensive characterization of the vibrational spectroscopy of the non-planar molecule thianthrene. The combination of infrared, Raman and inelastic neutron scattering spectroscopies is highly complementary and allows all of the modes to be observed. Periodic density-functional theory calculations have provided unambiguous assignments of the spectra. The literature states that C–S stretch modes occur in the 600–800 cm
−1
range. We find that while there are modes that involve sulfur motion in this region, this is a consequence of motion in the
ortho
-phenylene rings. The modes that are driven by the C–S stretches are found in the ~400–500 cm
−1
range. The C–S–C bending modes occur in the 200–300 cm
−1
range; these have not been previously characterized.
Bacterial profile of wound site infections and evaluation of risk factors for sepsis among road traffic accident (RTA) patients from Apex trauma centre, Northern India
Authors: Singh Aparna , Singh Patel Sangram , Sahu Chinmoy , Singh Amit Kumar , Tejan Nidhi , Varghese Gerlin , Singh Pooja , Ghar Malay
Published: May 2024

Background

There is limited data about the bacterial contamination of Road traffic accident (RTA) wounds and their antibiotic susceptibility patterns.

Materials and Methods

This prospective study was conducted in a tertiary care centre in Northern India from January 2023 to January 2024. Wound deep swabs and aspirates were collected from RTA patients presenting to Apex Trauma centre. Gram stain and culture were performed and the isolates were subjected to antibiotic susceptibility testing. Organism identification was done using MALDI-TOF MS. Blood samples were also collected to rule out blood stream infections during follow up if patient became febrile or shown symptoms of systemic infection.

Results

A total of 189 wound samples were collected in which 97 (51.32%) samples showed the growth of microorganisms. The isolates included 69 (71.13%) Gram-negative bacilli in which majority were Klebsiella pneumoniae and 28 (28.86%) Gram-positive cocci in which majority were Staphylococcus aureus. 22 (11.64%) patients died during the hospital course. Sepsis developed in 50 (26.45%) patients in which Gram-negative bacilli were the predominant microorganism. Risk factors evaluated as significant for sepsis were raised procalcitonin level, low Glasgow coma scale score (GCS), higher injury severity score (ISS), need for mechanical ventilation, raised qSOFA (quick sequential organ failure assessment) score. Among the Gram negative isolates, 100% susceptibility was seen for colistin. Among the Staphylococcus aureus, 100% susceptibility was seen for vancomycin, teicoplanin and levonadifloxacin.

Conclusion

It is essential to ascertain the profile of microorganism isolated from RTA wounds in order to reduce antimicrobial resistance and to deliver efficient treatment.
Detection of Hepatitis B Virus Genotypes in a Group of Hepatitis B Virus Infected Patients in Central and Northern Sri Lanka
Authors: Pattiyakumbura T T , Malkanthi K.G.K , Manamperi A. , Dheerasekara W.K.H , Muthugala M.A.R.V.
Published: May 2024

Introduction

Hepatitis B infection causes a spectrum of clinical diseases varying from asymptomatic infection to severe or fulminant acute hepatitis, chronic liver disease, cirrhosis, and hepatocellular carcinoma. Hepatitis B virus genotypes appear to influence transmission dynamics, clinical outcomes, and responses to antiviral therapy. However, hepatitis B genotyping is a poorly investigated topic in Sri Lanka. This study intended to determine hepatitis B genotypes in a group of HBV-infected persons in central and northern Sri Lanka.

Methodology

The study was a laboratory-based descriptive cross-sectional study. Initial detection of HBV DNA in EDTA blood samples was done by a commercially validated quantitative real-time polymerase chain reaction kit (qPCR). Hepatitis B genotyping was performed by in-house conventional semi-nested multiplex PCR using genotype-specific primers (for genotypes A, B, C, D, E, F). The serological profile was determined using a commercially validated ELISA/ CLIA assay. The results were evaluated for the genotype prevalence, viral load association, and HBeAg expression in the study population.

Results and Conclusion

The study detected that genotype C is most prevalent and infections with multiple genotypes (52%) were commoner than mono-genotype (23%) infections. In 25% of patients, had no detectable genotype among genotype A-F. The mean viral load in asymptomatic patients with a single genotype was 3.28 log 10 copies/mL and in multiple genotypes was 4.18 log 10 copies/mL before treatment. Statistical significance was not detected in mean viral loads and HBeAg expression in these two groups. In the future, chronic HBV infection may be effectively treated and managed according to the infected genotype.
Chemoresistance to additive PARP/PI3K dual inhibition in triple-negative breast cancer cell lines is associated with adaptive stem cell-like prevalence
Authors: Petrella Paula E. , Chen Jason W. , Ravelo Gabrielle O. , Cosgrove Benjamin D.
Published: May 2024

Cancer stem-like cells (CSCs) are posited to exhibit specialized oncogenic capacity to drive malignancies. CSCs are distinguished by enhanced hallmarks of cancer, including apoptosis avoidance, phenotypic plasticity and aberrant growth pathway signaling. Standard-of-care chemotherapies targeted to rapidly cycling cells routinely fail to eliminate this resistant subpopulation, leading to disease recurrence and metastasis. Triple-negative breast cancer (TNBC), a highly aggressive subtype of breast cancer, is enriched for tumor-propagating CD44+/CD24−/lowCSCs, which are poorly ablated by chemotherapeutics and are associated with poor prognosis. CD44 governs sustained PI3K signaling in breast cancer, which is essential for CSC maintenance. PI3K inhibition can elicit DNA damage and down-regulate BRCA1 expression, which in turn enhance the synthetic lethality of PARP inhibitors. Here, we examined a dual chemotherapeutic approach targeting these pathways by combining a pan-PI3K inhibitor (Buparlisib) and a PARP1 inhibitor (Olaparib) on a panel of TNBC cell lines with distinct mutational profiles and proportions of CSCs. We observed differential sensitivity to this dual inhibition strategy and varying cellular stress and resistance responses across eight TNBC lines. The dual chemotherapeutic effect is associated with a reduction in S-phase cells, an increased in apoptotic cells and elevated expression of cleaved PARP, indicating a provoked replicative stress response. We observed that PARP/PI3K inhibition efficacy was potentiated by repeated administration in some TNBC lines and identified critical treatment schedules, which further potentiated the dual chemotherapeutic effect. Dual inhibition induced small but significant increases in CSC relative abundance as marked by CD44+/CD24−/lowor ALDH1+cells and increased stress and survival signaling in multiple TNBC cell lines, suggesting this sub-population contributes to TNBC chemoresistance. These results suggest the additive effects of PARP and PI3K inhibition against CSC phenotypes may be enhanced by temporally-staged administration in TNBC cells.
ExploringAlu-Driven DNA Transductions in the Primate Genomes
Authors: Halabian Reza , Storer Jessica M. , Hoyt Savannah J. , Hartley Gabrielle A. , Brosius Jürgen , O’Neill Rachel J. , Makałowski Wojciech
Published: May 2024

Long terminal repeats (LTRs) and non-LTRs retrotransposons, aka retroelements, collectively occupy a substantial part of the human genome. Certain non-LTR retroelements, such as L1 and SVA, have the potential for DNA transduction, which involves the concurrent mobilization of flanking non-transposon DNA during retrotransposition. These events can be detected by computational approaches. Despite being the most abundant short interspersed sequences (SINEs) that are still active within the genomes of humans and other primates, the transduction rate caused byAlusequences remains unexplored. Therefore, we conducted an analysis to address this research gap and utilized an in-house program to probe for the presence ofAlu-related transductions in the human genome. We analyzed 118,489 full-lengthAluY subfamilies annotated within the first complete human reference genome, T2T-CHM13. For comparative insights, we extended our exploration to two non-human primate genomes, the chimpanzee and the rhesus monkey. After manual curation, our findings did not confirm anyAlu-mediated transductions, whose source genes are, unlike L1 or SVA, transcribed by RNA polymerase III, implying that they are infrequent or possibly absent not only in the human but also in chimpanzee and rhesus monkey genomes. Although we identified loci in which the 3’ Target Site Duplication (TSD) was located distantly from the retrotransposedAluYs, a transduction hallmark, our study could not find further support for such events. The observation of these instances can be explained by the incorporation of other nucleotides into the poly(A) tails in conjunction with polymerase slippage.
Structure of a human monoclonal antibody in complex with Outer surface protein C (OspC) of the Lyme disease spirochete,Borreliella burgdorferi
Authors: Rudolph Michael J. , Chen Yang , Vorauer Clint , Vance David J , Piazza Carol Lyn , Willsey Graham G , McCarthy Kathleen , Muriuki Beatrice , Cavacini Lisa A. , Guttman Miklos , Mantis Nicholas J
Published: May 2024

Lyme disease is a tick-borne, multisystem infection caused by the spirochete,Borreliella burgdorferi. Although antibodies have been implicated in the resolution of Lyme disease, the specific B cell epitopes targeted during human infections remain largely unknown. In this study, we characterized and defined the structural epitope of a patient-derived bactericidal monoclonal IgG (“B11”) against Outer surface protein C (OspC), a homodimeric lipoprotein necessary forB. burgdorferitick-mediated transmission and early-stage colonization of vertebrate hosts. High-resolution epitope mapping was accomplished through hydrogen deuterium exchange-mass spectrometry (HDX-MS) and X-ray crystallography. Structural analysis of B11 Fab-OspCAcomplexes revealed the B11 Fabs associated in a 1:1 stoichiometry with the lateral faces of OspCAhomodimers such that the antibodies are essentially positioned perpendicular to the spirochete’s outer surface. B11’s primary contacts reside within the membrane proximal regions of α-helices 1 and 6 and adjacent loops 5 and 6 in one OspCAmonomer. In addition, B11 spans the OspCAdimer interface, engaging opposing α-helix 1’, α-helix 2’, and loop 2-3’ in the second OspCAmonomer. The B11-OspCAstructure is reminiscent of the recently solved mouse transmission blocking monoclonal IgG B5 in complex with OspCA, indicating a mode of engagement with OspC that is conserved across species. In conclusion, we provide the first detailed insight into the interaction between a functional human antibody and an immunodominant Lyme disease antigen long considered an important vaccine target.
Genome-wide association for loci influencing thermal performance curves inNeurospora crassa
Authors: Räsänen Emmi , Moghadam Neda N. , Sidhu Karendeep , Summanen Pauliina A. M. , Littunen Henna-Riikka , Ketola Tarmo , Kronholm Ilkka
Published: May 2024

Temperature poses a unique challenge to ectothermic species, as it affects all biochemical reactions in the cell and causes physiological stress. The effect of temperature on an organism can be described by a thermal performance curve (TPC), which displays organismal performance, such as growth rate, as a function of temperature. Previous studies on thermal performance have revealed different amounts of genetic variation and trade-offs in TPC shape and position within species and populations. However, very little is known about the genetic architecture of TPCs on the level of individual loci and alleles. We asked what is the identity of loci contributing to genetic variation in TPCs, and do the alleles exhibit trade-offs or thermodynamic scaling across the temperature range? We used genome-wide association mapping to find loci influencing growth rate at different temperatures and TPC traits in the filamentous fungusNeurospora crassa. We also evaluated the directions and magnitudes of allelic effects to investigate possible trade-offs. We observed both unique associations at specific temperatures, as some loci affected growth rate only at low, intermediate, or high temperatures, and associations that were shared across multiple temperatures. However, only weak evidence of trade-offs was detected, indicating that the evolution of TPCs inN. crassais not constrained by allelic effects in opposite directions at hot and cold temperatures. Our findings indicate that trade-offs contribute little to variation in TPCs.
Engineering bacterial protein polymers to support human pluripotent stem cell growth and differentiation in culture
Authors: Creigh Adam R. , Waller Helen , Lakey Jeremy H. , Chrzanowska-Lightowlers Zofia M. , Lightowlers Robert N. , Peters Daniel T.
Published: May 2024

Induced pluripotent stem cells (iPSCs) are of significant value due to their wide ranging potential, removing the need for embryonic material. To successfully culture, expand and differentiate these cells, it is crucial to maintain a precise biological environment, including an appropriate attachment substrate. Commonly used attachment substrates include recombinant extracellular matrix (ECM) components like vitronectin, as well as animal-derived ECM mixes such as GelTrex and Matrigel. However, there is growing interest in exploring alternative approaches to support bioactivity of cells. One approach that is gaining traction is the use of the Caf1 protein ofYersinia pestis. This protein is appealing primarily due to its stability, modularity, and ease of production. In this study, we have developed novel variants of Caf1 that effectively support the growth and differentiation of iPSCs, performing at least as well as GelTrex. Our findings highlight the potential of Caf1 laminin and vitronectin mimics as viable alternatives for supporting iPSC growth and differentiation. The successful development of these Caf1 variants opens new avenues for the field, paving the way for better defined, more cost-effective and readily available attachment substrates in iPSC research and applications.
A claudin5-binding peptide enhances the permeability of the blood-brain-barrier
Authors: Trevisani Martina , Berselli Alessandro , Alberini Giulio , Centonze Eleonora , Vercellino Silvia , Cartocci Veronica , Millo Enrico , Ciubanu Dinu Zinovie , Armirotti Andrea , Pisani Francesco , Zara Federico , Castagnola Valentina , Maragliano Luca , Benfenati Fabio
Published: May 2024

The blood-brain barrier (BBB) is essential to maintain brain homeostasis and healthy conditions but it also prevents drugs from reaching brain cells. In the BBB, tight junctions (TJs) are multi-protein complexes located at the interface between adjacent brain endothelial cells that regulate paracellular diffusion and claudin-5 (CLDN5) is the major component of the TJ portfolio, playing a pivotal role in restricting the paracellular traffic. In view of obtaining fine control over the transport across the BBB, the use of competing peptides able to bind CLDN5 to induce transient and regulated permeabilization of the paracellular passage is emerging as a potentially translatable strategy for clinical applications. In this work, we designed and tested short peptides with improved solubility and biocompatibility using a combined approach that involved structural modeling techniques andin vitrovalidation, generating a robust workflow for the design, screening, and optimization of peptides for the modulation of the BBB paracellular permeability. We designed a selection of 11- to 16-mer compounds derived from the first CLDN5 extracellular domain and from the CLDN5-binding domain ofClostridium perfringensenterotoxin and determined their efficiency in enhancing BBB permeability. The computational analysis classified all tested peptides based on solubility and affinity to CLDN5, and provided atom-level details of the binding process. From our screening, we identified a novel CLDN5-derived peptide, here calledf1-C5C2, which demonstrated good solubility in biological media, efficient binding to CLDN5 subunits, and capability to increase permeability at low concentrations. The peptidomimeticin silico/in vitrostrategy described here can achieve a transient and reversible permeabilization of the BBB with potential applications in the pharmacological treatment of brain diseases.

HIGHLIGHTS

Water-soluble peptidomimetics are used to competitively bind claudin-5 tight junction proteins and increase the permeability of the blood-brain barrier;

Trans-endothelial electrical resistance and dissociation constant measurements demonstrate the binding affinity of the peptidef1-C5C2for claudin-5;

Unbinding free energy calculations correlated with experimental results and provided information on the protein-peptide binding interface.

Incubation with the peptidef1-C5C2allows paracellular transport of 4K, but not 70K, dextran.

GRAPHICAL ABSTRACT
Polymer Collapse & Liquid-Liquid Phase-Separation are Coupled in a Generalized Prewetting Transition
Authors: Rouches Mason N. , Machta Benjamin B.
Published: May 2024

The three-dimensional organization of chromatin is thought to play an important role in controlling gene expression. Specificity in expression is achieved through the interaction of transcription factors and other nuclear proteins with particular sequences of DNA. At unphysiological concentrations many of these nuclear proteins can phase-separate in the absence of DNA, and it has been hypothesized that, in vivo, the thermodynamic forces driving these phases help determine chromosomal organization. However it is unclear how DNA, itself a long polymer subject to configurational transitions, interacts with three-dimensional protein phases. Here we show that a long compressible polymer can be coupled to interacting protein mixtures, leading to ageneralized prewettingtransition where polymer collapse is coincident with a locally stabilized liquid droplet. We use lattice Monte-Carlo simulations and a mean-field theory to show that these phases can be stable even in regimes where both polymer collapse and coexisting liquid phases are unstable in isolation, and that these new transitions can be either abrupt or continuous. For polymers with internal linear structure we further show that changes in the concentration of bulk components can lead to changes in three-dimensional polymer structure. In the nucleus there are many distinct proteins that interact with many different regions of chromatin, potentially giving rise to many different Prewet phases. The simple systems we consider here highlight chromatin’s role as a lower-dimensional surface whose interactions with proteins are required for these novel phases.
Toll-Like-Receptor 5 protects against pulmonary fibrosis by reducing lung dysbiosis
Authors: Sakamachi Yosuke , Wiley Emma , Solis Alma , Johnson Collin G , Meng Xianglin , Hussain Salik , Lipinski Jay H , O’Dwyer David N , Randall Thomas , Malphurs Jason , Papas Brian , Wu Benjamin G , Li Yonghua , Kugler Matthias , Mehta Sanya , Trempus Carol S , Thomas Seddon Y , Li Jian-Liang , Zhou Lecong , Karmaus Peer W , Fessler Michael B , McGrath John A , Gibson Kevin , Kass Daniel J , Gleiberman Anatoli , Walts Avram , Invernizzi Rachele , Molyneaux Phil L , Yang Ivana V , Zhang Yingze , Kaminski Naftali , Segal Leopoldo N , Schwartz David A , Gudkov Andrei V , Garantziotis Stavros
Published: May 2024

Idiopathic pulmonary fibrosis (IPF) is a devastating pulmonary disease with no curative treatment other than lung transplantation. IPF results from maladaptive responses to lung epithelial injury, but the underlying mechanisms remain unclear. Here, we show that deficiency in the innate immune receptor, toll-like receptor 5 (TLR5), is associated with IPF in humans and with increased susceptibility to epithelial injury and experimental fibrosis in mice, while activation of lung epithelial TLR5 through a synthetic flagellin analogue protects from experimental fibrosis. Mechanistically, epithelial TLR5 activation induces antimicrobial gene expression and ameliorates dysbiosis after lung injury. In contrast, TLR5 deficiency in mice and IPF patients is associated with lung dysbiosis. Elimination of the microbiome in mice through antibiotics abolishes the protective effect of TLR5 and reconstitution of the microbiome rescues the observed phenotype. In aggregate, TLR5 deficiency is associated with IPF and dysbiosis in humans and in the murine model of pulmonary fibrosis. Furthermore, TLR5 protects against pulmonary fibrosis in mice and this protection is mediated by effects on the microbiome.

One-sentence summary

Deficiency in the innate immune receptor TLR5 is a risk factor for pulmonary fibrosis, because TLR5 prevents microbial dysbiosis after lung injury.
Finding the right words to evaluate research: An empirical appraisal of eLife’s assessment vocabulary
Authors: Hardwicke Tom E. , Schiavone Sarah R. , Clarke Beth , Vazire Simine
Published: May 2024

Research articles published by the journal eLife are accompanied by short evaluation statements that use phrases from a prescribed vocabulary to evaluate research on two dimensions: importance and strength of support. Intuitively, the prescribed phrases appear to be highly synonymous (e.g., important/valuable, compelling/convincing) and the vocabulary’s ordinal structure may not be obvious to readers. We conducted an online repeated-measures experiment to gauge whether the phrases were interpreted as intended. We also tested an alternative vocabulary with (in our view) a less ambiguous structure. 301 participants with a doctoral or graduate degree used a 0-100% scale to rate the importance and strength of support of hypothetical studies described using phrases from both vocabularies. For the eLife vocabulary, most participants’ implied ranking did not match the intended ranking on both the importance (n= 59, 20% matched, 95% confidence interval [15% to 24%]) and strength of support dimensions (n= 45, 15% matched [11% to 20%]). By contrast, for the alternative vocabulary, most participants’ implied ranking did match the intended ranking on both the importance (n= 188, 62% matched [57% to 68%]) and strength of support dimensions (n= 201, 67% matched [62% to 72%]). eLife’s vocabulary tended to produce less consistent between-person interpretations, though the alternative vocabulary still elicited some overlapping interpretations away from the middle of the scale. We speculate that explicit presentation of a vocabulary’s intended ordinal structure could improve interpretation. Overall, these findings suggest that more structured and less ambiguous language can improve communication of research evaluations.
Structural basis of the bacterial flagellar motor rotational switching
Authors: Tan Jiaxing , Zhang Ling , Zhou Xingtong , Han Siyu , Zhou Yan , Zhu Yongqun
Published: May 2024

The bacterial flagellar motor is a huge bidirectional rotary nanomachine that drives rotation of the flagellum for bacterial motility1–5. The cytoplasmic C ring of the flagellar motor functions as the switch complex for the rotational direction switching from counterclockwise to clockwise2,3,6–9. However, the structural basis of the rotational switching and how the C ring is assembled have long remained elusive. Here, we present two high-resolution cryo-electron microscopy structures of the C ring-containing flagellar motor-hook complex fromSalmonellaTyphimurium, which are in the default counterclockwise state and in a constitutively active CheY mutant-induced clockwise state, respectively. In both complexes, the C ring consists of four subrings, but is in two different conformations. The CheY proteins are bound into an open groove between two adjacent protomers on the surface of the middle subring of the C ring and interact with the FliG and FliM subunits. The binding of the CheY protein induces a significant upward shift of the C ring towards the MS ring and inward movements of its protomers towards the motor center, which eventually remodels the structures of the FliG subunits and reverses the orientations and surface electrostatic potential of the αtorquehelices to trigger the counterclockwise-to-clockwise rotational switching. The conformational changes of the FliG subunits reveal that the stator units on the flagellar motors require a relocation process in the bacterial inner membrane during the rotational switching. This study provides unprecedented molecular insights into the rotational switching mechanism and a detailed overall structural view of the bacterial flagellar motors.
IFI207, a young and fast-evolving protein, controls retroviral replication via the STING pathway
Authors: Moran Eileen A. , Salas-Briceno Karen , Zhao Wenming , Enya Takuji , Aguilera Alexya N. , Acosta Ivan , Alonzo Francis , Kiani Dara , Behnsen Judith , Alvarez Catalina , Keane Thomas M. , Adams David J. , Lilue Jingtao , Ross Susan R.
Published: May 2024

Mammalian AIM-2-like receptor (ALR) proteins bind nucleic acids and initiate production of type I interferons or inflammasome assembly, thereby contributing to host innate immunity. In mice, theAlrlocus is highly polymorphic at the sequence and copy number level and we show here, is one of the most dynamic regions of the genome. One rapidly evolving gene within this region,Ifi207, was introduced to theMusgenome by gene conversion or an unequal recombination event a few million years ago.Ifi207has a large, distinctive repeat region that differs in sequence and length amongMusspecies and even closely related inbredMus musculusstrains. We show that IFI207 controls MLV infectionin vivoand that it plays a role in the STING-mediated response to cGAMP, dsDNA, DMXXA and MLV. IFI207 binds to STING and inclusion of its repeat region appears to stabilize STING protein. TheAlrlocus andIfi207provide a clear example of the evolutionary innovation of gene function, possibly as a result of host-pathogen co-evolution.

IMPORTANCE

The Red Queen hypothesis predicts that the arms race between pathogens and the host may accelerate evolution of both sides, and therefore cause higher diversity in virulence factors and immune-related proteins, respectively (1). TheAlrgene family in mice has undergone rapid evolution in the last few million years and includes the creation of two novel members,MndaLandIfi207.Ifi207in particular became highly divergent, with significant genetic changes between highly related inbred mice. IFI207 protein acts in the STING pathway and contributes to anti-retroviral resistance via a novel mechanism. The data show that under the pressure of host-pathogen coevolution in a dynamic locus, gene conversion and recombination between gene family members creates new genes with novel and essential functions that play diverse roles in biological processes.
Scoping review of free evidence summary sources available online, relevant to occupational therapists working with children/youth, and families
Authors: Muir Philip , Dunford Carolyn
Published: May 2024

Purpose

Evidence-based practice is a professional standard for occupational therapists, but limited time, resources and knowledge challenge its implementation. This study aims to identify what free evidence summary sources (FESS) can be found through a simple online search, related to child/youth interventions surrounding cerebral palsy (CP), autism spectrum disorder (ASD), developmental coordination disorder (DCD), mental health or attention-deficit/hyperactivity disorder (MH/ADHD). Evidence summaries share research in concise, time-efficient manners.

Design/methodology/approach

An internet-based scoping review was conducted between February 2022 and July 2022, using Google, and known evidence summary producers. Evidence summaries meeting the inclusion criteria were located and catalogued. Type of agency, target audiences, purpose and distribution of evidence summaries related to diagnosis were identified for each FESS.

Findings

Ten FESS were found, which produced 113 intervention-focused evidence summaries within the past 10 years. These FESS were aimed at a variety of target audiences: service providers, service users, parents/families, researchers and commissioners, and were produced primarily by non-profit/charity organisations (6 of 10) who were trying to fill a gap in evidence. Forty-eight evidence summaries were related to ASD, 34 to CP, 29 to MH/ADHD and two to DCD.

Originality/value

A catalogue of FESS that exist online was produced, to support evidence-based practice for paediatric occupational therapists with limited resources, and may support improved health promotion and informed decision-making for service users. No consistent framework for FESS evidence summaries exists at this time.
Towards a critical realism synthesis of configurational and middle-range theorising
Authors: Malik Mohsin , Ali Imran
Published: May 2024

Purpose

We present configurational theorising as a novel approach to developing middle-range theory in two steps: (1) we illustrate configurational theorising as a new form of supply chain inquiry by connecting its philosophical assumptions with a methodological execution, and (2) we generate new insights underpinning a middle-range theory for supply chain resilience.

Design/methodology/approach

We synthesise information from a range of sources and invoke ‘critical realism” to suggest a five-phase configurational theorising roadmap to develop middle-range theory. We demonstrate this roadmap to explain supply chain resilience by analysing qualitative data from 22 organisations within the Australian food supply chain.

Findings

Coopetition and supply chain collaboration are necessary causal conditions, but they need to combine with either supply chain agility or multi-sourcing strategy to build supply chain resilience. Asymmetrical analyses showed that the simultaneous absence of supply chain collaboration, supply chain agility and multi-sourcing results in low supply chain resilience, but coopetition was indifferent to low supply chain resilience. Similarly, high supply chain resilience is possible with the non-presence of supply chain agility and multi-sourcing.

Research limitations/implications

The configurational middle-range theorising roadmap presented and empirically tested in this paper constitutes a substantial advancement to both theory and the methodological domain.

Originality/value

This is the first attempt at developing a middle-range theory for supply chains by explicitly drawing on configurational theorising.
Determinants of Islamic fintech adoption: a systematic literature review
Authors: Maniam Shatheish
Published: May 2024

Purpose

Sharia-compliant financial technologies (Islamic fintech) are becoming increasingly popular among Muslims and non-Muslims. As the Islamic fintech landscape continues to grow and transform, it is crucial to understand the factors that influence the acceptance or adoption of Islamic fintech services from the past literature. Therefore, this paper aims to conduct a systematic literature review (SLR) to investigate and compile factors that could influence a user to adopt Islamic fintech.

Design/methodology/approach

The current study adopted the systematic literature review approach using Preferred Reporting Items for Systematic Reviews and Meta-Analyses technique to examine research on Islamic fintech adoption. A set of inclusion criteria was applied to filter out irrelevant documents and ensure the selection of only the most relevant ones. The criteria were limited to quantitative journals published in English between 2012 and 2022, as identified in Scopus outlets.

Findings

Despite the existence of various theoretical frameworks, the technology acceptance model and Unified Theory of Acceptance and Use of Technology 2 frameworks have gained prominence as the most frequently applied frameworks in examining Islamic fintech adoption. In addition, trust is the most important self-developed construct for the adoption of Islamic Fintech.

Research limitations/implications

The current study does not segregate the intention, actual usage and retention, as the author is interested in understanding the overall adoption of Islamic fintech services. To obtain more specific analysis results, future research could potentially separate the three types of adoption exposure, i.e., consumer acceptance, intention and retention. Next, future studies can also expand their analysis and gain a better understanding of the research topic by exploring alternative data sources such as Web of Science, ERA or JSTOR.

Originality/value

To the best of the author’s knowledge, this study makes a significant contribution to the literature by providing the first systematic literature review of factors influencing fintech adoption from an Islamic perspective.