bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the Role of Nicotine Stereoisomer on Nicotine Pouch Abuse Liability: A Randomized Crossover Trial
Authors: Keller-Hamilton Brittney , Curran Hayley , Alalwan Mahmood , Hinton Alice , Brinkman Marielle C , El-Hellani Ahmad , Wagener Theodore L , Chrzan Kirsten , Atkinson Leanne , Suraapaneni Sriya , Mays Darren
Published: May 2024

Introduction

Many oral nicotine pouch (ONP) brands use synthetic nicotine, which typically contains a racemic (50:50) mixture of nicotine’s two stereoisomers: S-nicotine and R-nicotine. Because tobacco-derived nicotine contains more than 99% S-nicotine, the effects of R-nicotine in humans are not well known. We compared systemic nicotine exposure and product appeal of ONPs containing more than 99% S-nicotine versus racemic nicotine.

Aims and Methods

N = 18 adult smokers (Mage = 45 years, 66.7% male, 77.8% White) enrolled in a three-visit single-blind, randomized crossover study. During each visit, participants used one wintergreen-flavored, 3 mg nicotine ONP for 30 min following at least12 h nicotine abstinence. Study ONP #1 contained more than 99% S-nicotine and the other two study ONPs contained racemic nicotine (collapsed for analyses). Plasma nicotine assessments and measures of withdrawal relief occurred at t = 0, 5, 15, 30, 60, and 90 min; measures of product appeal were assessed following ONP use.

Results

Using the ONP with more than 99% S-nicotine resulted in greater plasma nicotine concentration from 15 to 90 min (p < .0001) and greater maximum plasma nicotine concentration than the ONPs with racemic nicotine (M = 9.9 ng/mL [SD = 2.5] vs. M = 5.7 ng/mL [SD = 2.8], respectively; p < .0001). Product liking and withdrawal relief were similar across ONPs, although participants reported more “bad effects” when using the ONP with more than 99% S-nicotine.

Conclusions

Participants reported few subjective differences in ONPs according to nicotine stereoisomer, but plasma nicotine concentration was greater for ONPs using more than 99% S-nicotine. ONPs with more than 99% S-nicotine (vs. racemic nicotine) might be better substitutes for cigarettes, but research into other ONP characteristics (eg flavors, freebase nicotine) is needed to inform regulation.

Implications

Little is known about the effects of racemic (vs. S-) nicotine in humans. In a sample of adults who smoke cigarettes, we identified that oral nicotine pouches containing racemic nicotine exposed participants to less nicotine than oral nicotine pouches containing only S-nicotine, but both types of oral nicotine pouches held similar, moderate appeal. Additional research evaluating the roles that flavorings, total nicotine concentration, and freebase nicotine play in the abuse liability of oral nicotine pouches would inform comprehensive product regulations to support public health.
Implementing Pictorial Health Warning Labels on Waterpipe Tobacco Products in Lebanon: A Policy Framework Analysis of Content, Actors, Context, and Process
Authors: Nakkash Rima , Mugharbil Sanaa , Tleis Malak , Jaafar Mariana , Asfar Taghrid , Maziak Wasim
Published: May 2024

Introduction

Lebanon has one of the world’s highest waterpipe (WP) consumption rates. Research has documented the effectiveness of implementing pictorial health warning labels (PHWLs) on WP products at encouraging smoking cessation and discouraging youth uptake of smoking.

Aims and Methods

This study aims to gain insight into key informants’ (KIs) views on the issuance, implementation, and compliance of a decree for PHWLs on WP products. Thirteen KIs (policy makers, media, and international/local nongovernment organization representatives) were interviewed online and asked about potential barriers and facilitators they saw to issuing and implementing a PHWL decree. They were shown examples of PHWLs and asked about processes needed for implementation and compliance. The policy triangle framework (content, actors, context, and process) was used to interpret findings.

Results

Although there was clear discrepancy and ambiguousness among the KIs’ views regarding process and actors, there was more consensus and clarity around context and content. Challenges to implementation were: (1) multiple sources of production and supply of WP, (2) uncertainty regarding the responsible actors for each step, (3) prioritization of a tobacco control decree amidst a political and economic crisis, and (4) challenges to practicality of applying PHWL on the WP given its multicomponent nature.

Conclusions

This research provides an in-depth understanding of KI’s views regarding content, actors, context, and process in relation to the issuance, implementation, and compliance to PHWLs on WP products. Noted challenges require careful consideration if progress is to be made to introduce PHWLs.

Implications

A growing research base has documented the potential effectiveness of PHWLs on reducing WP consumption. Findings of this study show that implementing PHWLs on WP products requires a distinct understanding of the policy environment and context, as well as content, actors, and processes. Implementing PHWLs on WP tobacco products needs to address the complex nature of WP smoking as a multicomponent tobacco use method.
A machine-learning-enabled smart neckband for monitoring dietary intake
Authors: Park Taewoong , Mahmud Talha Ibn , Lee Junsang , Hong Seokkyoon , Park Jae Young , Ji Yuhyun , Chang Taehoo , Yi Jonghun , Kim Min Ku , Patel Rita R , Kim Dong Rip , Kim Young L , Lee Hyowon , Zhu Fengqing , Lee Chi Hwan
Published: May 2024

The increasing need for precise dietary monitoring across various health scenarios has led to innovations in wearable sensing technologies. However, continuously tracking food and fluid intake during daily activities can be complex. In this study, we present a machine-learning-powered smart neckband that features wireless connectivity and a comfortable, foldable design. Initially considered beneficial for managing conditions such as diabetes and obesity by facilitating dietary control, the device's utility extends beyond these applications. It has proved to be valuable for sports enthusiasts, individuals focused on diet control, and general health monitoring. Its wireless connectivity, ergonomic design, and advanced classification capabilities offer a promising solution for overcoming the limitations of traditional dietary tracking methods, highlighting its potential in personalized healthcare and wellness strategies.
Application of magnetism in tissue regeneration: recent progress and future prospects
Authors: Guan Wenchao , Gao Hongxia , Liu Yaqiong , Sun Shaolan , Li Guicai
Published: May 2024

Tissue regeneration is a hot topic in the field of biomedical research in this century. Material composition, surface topology, light, ultrasonic, electric field and magnetic fields (MFs) all have important effects on the regeneration process. Among them, MFs can provide nearly non-invasive signal transmission within biological tissues, and magnetic materials can convert MFs into a series of signals related to biological processes, such as mechanical force, magnetic heat, drug release, etc. By adjusting the MFs and magnetic materials, desired cellular or molecular-level responses can be achieved to promote better tissue regeneration. This review summarizes the definition, classification and latest progress of MFs and magnetic materials in tissue engineering. It also explores the differences and potential applications of MFs in different tissue cells, aiming to connect the applications of magnetism in various subfields of tissue engineering and provide new insights for the use of magnetism in tissue regeneration.
Periapical lesion-derived decellularized extracellular matrix as a potential solution for regenerative endodontics
Authors: Hu Nan , Jiang Ruixue , Deng Yuwei , Li Weiping , Jiang Wentao , Xu Ningwei , Wang Jia , Wen Jin , Gu Shensheng
Published: May 2024

Pulp regeneration remains a crucial target in the preservation of natural dentition. Using decellularized extracellular matrix is an appropriate approach to mimic natural microenvironment and facilitate tissue regeneration. In this study, we attempted to obtain decellularized extracellular matrix from periapical lesion (PL-dECM) and evaluate its bioactive effects. The decellularization process yielded translucent and viscous PL-dECM, meeting the standard requirements for decellularization efficiency. Proteomic sequencing revealed that the PL-dECM retained essential extracellular matrix components and numerous bioactive factors. The PL-dECM conditioned medium could enhance the proliferation and migration ability of periapical lesion-derived stem cells (PLDSCs) in a dose-dependent manner. Culturing PLDSCs on PL-dECM slices improved odontogenic/angiogenic ability compared to the type I collagen group. In vivo, the PL-dECM demonstrated a sustained supportive effect on PLDSCs and promoted odontogenic/angiogenic differentiation. Both in vitro and in vivo studies illustrated that PL-dECM served as an effective scaffold for pulp tissue engineering, providing valuable insights into PLDSCs differentiation. These findings pave avenues for the clinical application of dECM’s in situ transplantation for regenerative endodontics.
Carboxypeptidase M modulates BMSCs osteogenesis–adipogenesis via the MAPK/ERK pathway: An integrated single‐cell and bulk transcriptomic study
Authors: Liao Zheting , Zheng Xiaoyong , Li Hongfang , Deng Zhonghao , Feng Shuhao , Tan Hongbo , Zhao Liang
Published: May 2024

The pathogenesis of osteoporosis (OP) is closely associated with the disrupted balance between osteogenesis and adipogenesis in bone marrow‐derived mesenchymal stem cells (BMSCs). We analyzed published single‐cell RNA sequencing (scRNA‐seq) data to dissect the transcriptomic profiles of bone marrow‐derived cells in OP, reviewing 56 377 cells across eight scRNA‐seq datasets from femoral heads (osteoporosis or osteopenia n = 5, osteoarthritis n = 3). Seventeen genes, including carboxypeptidase M (CPM), were identified as key osteogenesis‐adipogenesis regulators through comprehensive gene set enrichment, differential expression, regulon activity, and pseudotime analyses. In vitro, CPM knockdown reduced osteogenesis and promoted adipogenesis in BMSCs, while adenovirus‐mediated CPM overexpression had the reverse effects. In vivo, intraosseous injection of CPM‐overexpressing BMSCs mitigated bone loss in ovariectomized mice. Integrated scRNA‐seq and bulk RNA sequencing analyses provided insight into the MAPK/ERK pathway's role in the CPM‐mediated regulation of BMSC osteogenesis and adipogenesis; specifically, CPM overexpression enhanced MAPK/ERK signaling and osteogenesis. In contrast, the ERK1/2 inhibitor binimetinib negated the effects of CPM overexpression. Overall, our findings identify CPM as a pivotal regulator of BMSC differentiation, which provides new clues for the mechanistic study of OP.
Controversies in Ileal Pouch-Anal Anastomosis for Ulcerative Colitis: A Systematic Review of Different Anastomotic Techniques
Authors: Kotze Paulo Gustavo , Avellaneda Nicolas , de Araujo Molteni Moretti Rafaela , Carvello Michele , Paoluzzi Tomada Elisa , Caserta de Campos Fabio Guilherme , Spinelli Antonino
Published: May 2024

BACKGROUND:

Available techniques for ileal pouch-anal anastomosis in ulcerative colitis include the handsewn, the double-stapled and the single-stapled anastomoses. There are controversies, indications, and different outcomes regarding these techniques.

OBJECTIVE:

To describe technical details, indications, and outcomes of 3 specific types of anastomoses in restorative proctocolectomy.

DATA SOURCE:

Systematic literature review for articles in the Pubmed database, according to PRISMA criteria.

STUDY SELECTION:

Studies describing outcomes of the 3 different types of anastomosis, during pouch surgery, in patients undergoing restorative proctocolectomy for ulcerative colitis.

INTERVENTION:

Ileal pouch-anal anastomosis technique.

MAIN OUTCOME MEASURES:

postoperative outcomes (anastomotic leaks, overall complication rates, pouch function).

RESULTS:

Twenty-one studies were initially included: 6 studies exclusively on single-stapled ileal pouch-anal anastomosis, 2 exclusively on double-stapled ileal pouch-anal anastomosis, 6 studies comparing single-stapled to double stapled techniques, 6 comparing double-stapled to hand-sewn ileal pouch-anal anastomosis, and 1 comprising single-stapled to hand-sewn ileal pouch-anal anastomosis. Thirty-seven studies were added according to authors' discretion as complementary evidence. Between 1990 and 2015, most studies were related to double-stapled ileal pouch-anal anastomosis, either only analyzing results of this technique, or comparing it with the handsewn technique. Studies published after 2015 were mostly related to transanal approaches to proctectomy for ileal pouch-anal anastomosis, in which a single-stapled anastomosis was introduced instead of the double-stapled, with some studies comparing both techniques.

LIMITATIONS:

Low number of studies with handsewn ileal pouch-anal anastomosis technique; large number of studies added at authors' discretion.

CONCLUSIONS:

Handsewn ileal pouch-anal anastomosis should be considered if a mucosectomy is performed for dysplasia or cancer in the low rectum or, possibly, for re-do surgery. Double-stapled ileal pouch-anal anastomosis has been more widely adopted for its simplicity and for the advantage of preserving the anal transition zone, having lower complications and adequate pouch function. The single-stapled ileal pouch-anal anastomosis offers a more natural design, is feasible and associated to reasonable outcomes when compared to double-stapled. See Video.
Efficacy of a New Hyaluronic Acid Dermal Filler on Nasolabial Folds Correction: A Prospective, Comparative, Double-Blinded Clinical Trial
Authors: Lheritier Céline , Converset Sophie , Rzany Berthold-Josef , Cartier Hugues , Ascher Benjamin
Published: May 2024

BACKGROUND

Hyaluronic acid–based dermal fillers are the cornerstones of wrinkle correction and facial contour redefinition.

OBJECTIVE

To assess the efficacy and safety of ESTLF compared with RESL for the treatment of nasolabial folds (NLFs).

MATERIALS AND METHODS

In this prospective, split-face, randomized, investigator and subject-blinded trial, 45 subjects with moderate-to-severe symmetrical NLFs were randomized to ESTLF on one side of the face and RESL on the other side and were followed up for 9 months. The primary end point was change in WSRS score from the baseline to Month 1 (M1). Secondary end points included changes in WSRS score at other time points, aesthetic improvement, wrinkle volume quantification, adverse events, and local tolerance.

RESULTS

The efficacy difference between ESTLF and RESL at M1 was in favor of ESTLF (−0.16, CI, −0.28 to −0.03]), demonstrating its noninferiority. Considering other time points, significant differences were observed at 3 and 6 months for ESTLF, assessed with WSRS, GAIS, or NLF volume quantification. Both treatments were well tolerated.

CONCLUSION

ESTLF is effective and well tolerated for the treatment of NLFs.
Cardiopulmonary Exercise Testing in Children With Long COVID: A Case-controlled Study
Authors: Baldi Fabiana , De Rose Cristina , Mariani Francesco , Morello Rosa , Raffaelli Francesca , Valentini Piero , Buonsenso Danilo
Published: May 2024

Background:

Cardiopulmonary exercise testing (CPET) is a noninvasive and nonexpensive diagnostic tool, that provides a comprehensive evaluation of the pulmonary, cardiovascular, and skeletal muscle systems’ integrated reactions to exercise. CPET has been extensively used in adults with Long COVID (LC), while the evidence about its role in children with this condition is scarce.

Methods:

Prospective, case-controlled observational study. Children with LC and a control group of healthy children underwent CPET. CPET findings were compared within the 2 groups, and within the LC groups according to main clusters of persisting symptoms.

Results:

Sixty-one children with LC and 29 healthy controls were included. Overall, 90.2% of LC patients (55 of 61) had a pathologic test vs 10.3% (3/29) of the healthy control. Children with LC presented a statistically significant higher probability of having abnormal values of peak VO2 (P = 0.001), AT% pred (P <0.001), VO2/HR % (P = 0.03), VO2 work slope (P = 0.002), VE/VCO2 slope (P = 0.01). The mean VO2 peak was 30.17 (±6.85) in LC and 34.37 (±6.55) in healthy patients (P = 0.007).

Conclusions:

Compared with healthy controls, children with LC have objective impaired functional capacity (expressed by a low VO2 peak), signs of deconditioning and cardiogenic inefficiency when assessed with CPET. As such, CPET should be routinely used in clinical practice to objectify and phenotype the functional limitations of children with LC, and to follow-up them.
RSV Severe Infection Risk Stratification in a French 5-Year Birth Cohort Using Machine-learning
Authors: Horvat Côme , Chauvel Cécile , Casalegno Jean-Sebastien , Benchaib Mehdi , Ploin Dominique , Nunes Marta C. ,   on behalf of the VRS Study Group in Lyon
Published: May 2024

Background:

Respiratory syncytial virus (RSV) poses a substantial threat to infants, often leading to challenges in hospital capacity. With recent pharmaceutical developments to be used during the prenatal and perinatal periods aimed at decreasing the RSV burden, there is a pressing need to identify infants at risk of severe disease. We aimed to stratify the risk of developing a clinically severe RSV infection in infants under 1 year of age.

Methods:

This retrospective observational study was conducted at the Hospices Civils de Lyon, France, involving infants born between 2014 and 2018. This study focused on infants hospitalized with severe and very severe acute lower respiratory tract infections associated with RSV (SARI-WI group). Data collection included perinatal information and clinical data, with machine-learning algorithms used to discriminate SARI-WI cases from nonhospitalized infants.

Results:

Of 42,069 infants, 555 developed SARI-WI. Infants born in November were very likely (>80%) predicted SARI-WI. Infants born in October were very likely predicted SARI-WI except for births at term by vaginal delivery and without siblings. Infants were very unlikely (<10%) predicted SARI-WI when all the following conditions were met: born in other months, at term, by vaginal delivery and without siblings. Other infants were possibly (10–30%) or probably (30–80%) predicted SARI-WI.

Conclusions:

Although RSV preventive measures are vital for all infants, and specific recommendations exist for patients with high-risk comorbidities, in situations where prioritization becomes necessary, infants born just before or within the early weeks of the epidemic should be considered as a risk group.
The Use of a Checklist to Optimize Electrolyte Replacement in the ICU
Authors: DePriest Jack , Nixon Joanna
Published: May 2024

Electrolyte replacement protocols are routinely used in intensive care units (ICU) to guide magnesium replacement. Guided by serum levels, these protocols include no patient-specific factors despite a literature showing ICU patients routinely have significant deficits despite normal serum levels. The authors developed a checklist to help identify patients requiring more aggressive magnesium replacement than the electrolyte replacement protocol would provide. The checklist included risk factors for having significant magnesium deficits and for developing arrhythmias. The checklist was retrospectively applied to 364 medical ICU patients. Diabetic patients prescribed outpatient diuretics were defined as the highest-risk population. A total of 88% of patients in this subgroup had normal magnesium levels. Despite averaging 3.4 risk factors per patient, only 3 of 32 patients received magnesium. Applying the checklist would have suggested additional repletion for at least 85% of patients. A checklist can help identify ICU patients who may require more aggressive magnesium supplementation than protocols will provide.
Intestinal pseudo-obstruction as systemic lupus erythematosus complication: is it time to reconsider the role of surgery?: A case report of a tailored multidisciplinary managed 44-year-old male patient
Authors: Romeo Mario , Dallio Marcello , Pellegrino Raffaele , Lucido Francesco Saverio , Parisi Simona , Gambardella Claudio , Panarese Iacopo , Russo Anna , Docimo Ludovico , Federico Alessandro
Published: May 2024

Rationale:

Intestinal pseudo-obstruction (IPO) represents an unclarified dysmotility disorder characterized by clinic-radiological signs of intestinal obstruction not associated with organic conditions. IPO may occur as a rare complication of autoimmune connective tissue diseases, including Systemic Lupus Erythematosus (SLE). Surgery is recognized as having a marginal management position for IPO patients: this case investigates its role, in the context of a multidisciplinary approach, in the diagnosis and treatment of acute complications of IPO.

Patient concerns:

An SLE-affected 44-year-old man with a history of recurring nonspecific abdominal sub-obstructive episodes was admitted to our department for constipation, vomiting, and unintentional weight loss. Clinical examination revealed a family history of eosinophilic gastroenteritis (EG). Laboratory tests, including Systemic Sclerosis screening, presented no significant alterations. Abdominal X-ray highlighted multiple air-fluid levels; contrast-enhanced CT showed fluid surrounding dilated loops, and fluid-filled ileal loops, without evidence of organic intrinsic/ab-extrinsic obstruction, perforation, or extraluminal gas. Considering these findings, stenosing-pattern Crohn disease and strictures-complicated EG were mainly suspected. However, ileum-colonoscopy with the histological analysis resulted in inconclusive for Crohn disease and EG.

Diagnosis:

The histological examination, by showing an SLE fibro-inflammatory pattern, not sparing the enteric plexus, infiltrating the intestinal wall of the surgical samples collected during the right hemicolectomy intervention, allowed the diagnosis of IPO.

Interventions and outcomes:

The patient, indeed, was initially managed conservatively with nasogastric decompression, immunosuppressive therapy, and parenteral nutrition by a multidisciplinary team including gastroenterologists, rheumatologists, and nutritionists. Unfortunately, 2 weeks later, the worsening symptoms required a lifesaving right hemicolectomy followed by ileostomy.

Lessons:

IPO should be suspected in SLE patients presenting treated-unresponsive GI symptoms. Its early recognition finalized to start a tailored multidisciplinary approach appears prognostically crucial. Surgery could represent a paramount diagnostic moment and therapeutic life-saving approach.
Liquid biomarkers in prostate cancer: recent advancements and future directions
Authors: Wong Chris Ho-Ming , Ko Ivan Ching-Ho , Ng Chi Fai
Published: May 2024

Purpose of review

Traditional diagnostic approaches of prostate cancer like PSA are limited by high false-positive rates and insufficient capture of tumour heterogeneity, necessitating the development of more precise tools. This review examines the latest advancements in liquid biomarkers for prostate cancer, focusing on their potential to refine diagnostic accuracy and monitor disease progression.

Recent findings

Liquid biomarkers have gained prominence because of their minimally invasive nature and ability to reflect the molecular characteristics of prostate cancer. Circulating tumour cells provide insight into tumour cell dissemination and are indicative of aggressive disease phenotypes, with single-cell analyses revealing genomic instability and treatment resistance. Circulating tumour DNA offers real-time tumour genomic information, aiding in treatment decision-making in advanced prostate cancer, where it has been associated with clinical progression. MicroRNAs act as oncogenes or tumour suppressors and exhibit diagnostic and prognostic potential; however, their clinical utility is constrained by the lack of consistent validation. Extracellular vesicles contain tumour-derived biomolecules, with specific proteins demonstrating prognostic relevance. Applications of these markers to urinary testing have been demonstrated.

Liquid biomarkers show potential in refining prostate cancer management. Future research should aim to integrate these biomarkers into a cohesive framework in line with precision medicine principles.
A Cerebellar Tumor-to-Tumor Metastasis in a Patient With Von Hippel-Lindau Disease
Authors: Wang Tengfei , Liu Lina , Rampisela Debby , Dong Xiuhua , Keith Kristin Alexndria , Benardete Ethan A. , Shan Frank Y.
Published: May 2024

Tumor-to-tumor metastasis in the central nerve system is uncommon in our routine practice. Most reports include metastatic breast cancer into meningioma. Here we report a metastatic clear cell renal cell carcinoma (ccRCC) into a cerebellar hemangioblastoma in a patient with von Hippel-Lindau (VHL) disease. Imaging cannot distinguish metastatic ccRCC from primary cerebellar hemangioblastoma. Immuno-molecular studies are proven to be diagnostic. We also reviewed previously documented tumor-to-tumor metastasis of ccRCC to cerebellar hemangioblastoma in VHL disease. Lastly, we discussed potential mechanisms involved in the metastasis of ccRCC to hemangioblastoma in the cerebellum in patients with VHL.
Bis(dimethylpyrazolyl)-aniline-
s
-triazine derivatives as efficient corrosion inhibitors for C-steel and computational studies
Authors: Hammud Hassan H. , Sheikh Nadeem S. , Shawish Ihab , Bukhamsin Hawra A. , Al-Hudairi Dolayl E. , Wee Angelina L. X. , Hamid Malai Haniti S. A. , Maache Sarah A. , Al-Rasheed Hessa H. , Barakat Assem , El-Faham Ayman , Abd El-Lateef Hany M.
Published: May 2024

4,6-Bis(3,5-dimethyl-
1H
-pyrazol-1-yl)-
N
-phenyl-1,3,5-triazin-2-amine (
PTA-1
),
N
-(4-bromophenyl)-4,6-bis(3,5-dimethyl-
1H
-pyrazol-1-yl)-1,3,5-triazin-2-amine (
PTA-2
) and 4,6-bis(3,5-dimethyl-
1H
-pyrazol-1-yl)-
N
-(4-methoxyphenyl)-1,3,5-triazin-2-amine (
PTA-3
) were synthesized and characterized. Their corrosion inhibition of carbon C-steel in 0.25 M H
2
SO
4
was studied by electrochemical impedance. The inhibition efficiency (IE%) of triazine was superior due to the cumulative inhibition of triazine core structure and pyrazole motif. Potentiodynamic polarizations suggested that
s
-triazine derivatives behave as mixed type inhibitors. The IE% values were 96.5% and 93.4% at 120 ppm for inhibitor
PTA-2
and
PTA-3
bearing –Br and –OCH
3
groups on aniline, respectively. While
PTA-1
without an electron donating group showed only 79.0% inhibition at 175 ppm. The adsorption of triazine derivatives followed Langmuir and Frumkin models. The values of adsorption equilibrium constant
K
°
ads
and free energy change Δ
G
°
ads
revealed that adsorption of inhibitor onto steel surface was favoured. A corrosion inhibition mechanism was proposed suggesting the presence of physical and chemical interactions. Density functional theory computational investigation corroborated nicely with the experimental results. Monte Carlo simulation revealed that the energy associated with the metal/adsorbate arrangement d
E
ads
/d
N
i
, for both forms of
PTA-2
and
PTA-3
with electron donating groups (−439.73 and −436.62 kcal mol
−1
) is higher than that of
PTA-1
molecule (−428.73 kcal mol
−1
). This aligned with experimental inhibition efficiency results.
Biogeographical ‍distributions of trickster animals
Authors: Shibasaki Shota , Nakadai Ryosuke , Nakawake Yo
Published: May 2024

Human language encompasses almost endless potential for meaning, and folklore can theoretically incorporate themes beyond time and space. However, actual distributions of the themes are not always universal and their constraints remain unclear. Here, we specifically focused on zoological folklore and aimed to reveal what restricts the distribution of trickster animals in folklore. We applied the biogeographical methodology to 16 taxonomic categories of trickster (455 data) and real (93 090 848 data) animals obtained from large databases. Our analysis revealed that the distribution of trickster animals was restricted by their presence in the vicinity and, more importantly, the presence of their corresponding real animals. Given that the distributions of real animals are restricted by the annual mean temperature and annual precipitation, these climatic conditions indirectly affect the distribution of trickster animals. Our study, applying biogeographical methods to culture, paves the way to a deeper understanding of the interactions between ecology and culture.
A mathematical framework for analysing particle flow in a network with multiple pools
Authors: Jain Aditi , Gupta Arvind Kumar
Published: May 2024

In many real-world systems, the entry rate of particles into a lane is affected by the occupancy of nearby pools. For instance, in biological networks, the concentration of molecules on the side of a membrane affects the entry of particles through the membrane. To understand the behaviour of such networks, we develop a network model of ribosome flow models (RFMs) having multiple pools where each RFM captures the dynamics of particle flow in a lane and competes for the finite resources present at the nearby pool. We study a ribosome flow model network with two pools (RFMNTP) and show that the network always admits a steady state. We then analyse the behaviour of the RFMNTP with respect to modifying the transition rate through a theoretical framework. Simulations of the RFMNTP demonstrate a counterintuitive result. For example, increasing any of the transition rates in the presence of a slow site in an RFM can increase the output rate of some RFMs and decrease the output rate of the other RFMs simultaneously. This suggests that the role of local sharing of particles incorporated is non-trivial. Finally, we illustrate how these results can provide insights into studying a network with multiple pools.
A novel insecticide impairs bumblebee memory and sucrose responsiveness across high and low nutrition
Authors: Gray Lily K. , Hulsey Marcus , Siviter Harry
Published: May 2024

Wild bees are important pollinators of crops and wildflowers but are exposed to a myriad of different anthropogenic stressors, such as pesticides and poor nutrition, as a consequence of intensive agriculture. These stressors do not act in isolation, but interact, and may exacerbate one another. Here, we assessed whether a field-realistic concentration of flupyradifurone, a novel pesticide that has been labelled as ‘bee safe’ by regulators, influenced bumblebee sucrose responsiveness and long-term memory. In a fully crossed experimental design, we exposed individual bumblebees (
Bombus impatiens
) to flupyradifurone at high (50% (w/w)) or low (15% (w/w)) sucrose concentrations, replicating diets that are either carbohydrate rich or poor, respectively. We found that flupyradifurone impaired sucrose responsiveness and long-term memory at both sucrose concentrations, indicating that better nutrition did not buffer the negative impact of flupyradifurone. We found no individual impact of sugar deficiency on bee behaviour and no significant interactions between pesticide exposure and poor nutrition. Our results add to a growing body of evidence demonstrating that flupyradifurone has significant negative impacts on pollinators, indicating that this pesticide is not ‘bee safe’. This suggests that agrochemical risk assessments are not protecting pollinators from the unintended consequences of pesticide use.
Scattering from time-modulated subwavelength resonators
Authors: Ammari Habib , Cao Jinghao , Hiltunen Erik Orvehed , Rueff Liora
Published: May 2024

We consider wave scattering from a system of highly contrasting resonators with time-modulated material parameters. In this setting, the wave equation reduces to a system of coupled Helmholtz equations that models the scattering problem. We consider the one-dimensional setting. In order to understand the energy of the system, we prove a novel higher-order discrete, capacitance matrix approximation of the subwavelength resonant quasi-frequencies. Further, we perform numerical experiments to support and illustrate our analytical results and show how periodically time-dependent material parameters affect the scattered wave field.
The Y498T499-SARS-CoV-2 Spike (S) protein variant interacts with rat ACE2 but does not infect or induce responses in the rat lung when delivered as a S-protein pseudotyped lentivirus
Authors: Green Amy L , Debellis Dylan , Cowell Evangeline , Lenchine Roman , Penn Timothy , Kris Luke P , McEvoy-May James , Bihari Shailesh , Dixon Dani-Louise , Carr Jillian M
Published: May 2024

The rat is a useful laboratory model for respiratory disease, and SARS-CoV-2 proteins such as the spike (S) protein can induce inflammation. This study has investigated the ability of the Q498Y, P499T (QP-YT) amino acid change described in the S-protein of the mouse adapted laboratory SARS-CoV-2 MA strain, to interact with rat angiotensin converting enzyme-2 (ACE2) and stimulate responses in rat lung. Using a real-time S-ACE2 quantitative fusion assay, ancestral S-protein fuses with human, but not rat ACE2. The QP-YT S-protein retains ability to fuse with human ACE2, and interacts with rat ACE2 in the fusion assay and using a S-protein pseudotyped lentivirus infection system. L452R S-protein did not bind to rat ACE2. Although rat lower lung contains both ACE2 and TMPRSS2 target cells, intratracheal delivery of ancestral or QP-YT S-protein pseudotyped lentivirus did not induce measurable respiratory changes, inflammatory infiltration, or innate mRNA responses. Isolation of primary cells from rat alveoli demonstrated the presence of cells expressing ACE2 and TMPRSS2. Infection of these cells, however with ancestral or QP-YT S-protein pseudotyped lentivirus was not observed. Analysis of the amino acid changes across the S-ACE2 interface highlights the Y498 interaction with H353 as a likely facilitator of binding to rat ACE2 but also other amino acids that could improve this interaction. Thus, rat lungs contain cells expressing receptors for SARS-CoV-2 and the QP-YT S-protein variant can bind to rat ACE2 but this does not result in infection or stimulate responses in the lung. Further amino acid changes in S-protein could enhance this interaction to improve the utility of the rat model for defining the role of the S-protein in driving inflammation in the lung.
Impact of Non-Contrast Enhanced Imaging Input Sequences on the Generation of Virtual Contrast-Enhanced Breast MRI Scans using Neural Networks
Authors: Liebert Andrzej , Schreiter Hannes , Kapsner Lorenz A , Eberle Jessica , Ehring Chris , Hadler Dominique , Brock Luise , Erber Ramona , Emons Julius , Laun Frederik B. , Uder Michael , Wenkel Evelyn , Ohlmeyer Sabine , Bickelhaupt Sebastian
Published: May 2024

Background

Virtual contrast-enhanced (vCE) imaging techniques are an emerging topic of research in breast MRI.

Purpose

To investigate how different combinations of T1-weighted (T1w), T2-weighted (T2w), and diffusion-weighted imaging (DWI) impact the performance of vCE breast MRI.

Materials and Methods

The IRB-approved, retrospective study included 1064 multiparametric breast MRI scans (age:52±12 years) obtained from 2017-2020 (single site, two 3T MRI). Eleven independent neural networks were trained to derive vCE images from varying input combinations of T1w, T2w, and multi-b-value DWI sequences (b-value=50–1500s/mm2). Three readers evaluated the vCE images with regards to qualitative scores of diagnostic image quality, image sharpness, satisfaction with contrast/signal-to-noise-ratio, and lesion/non-mass enhancement conspicuity. Quantitative metrics (SSIM, PSNR, NRMSE, and median symmetrical accuracy) were analyzed and statistically compared between the input combinations for the full breast volume and both enhancing and non-enhancing target findings.

Results

The independent test set consisted of 187 cases. The quantitative metrics significantly improved in target findings when multi-b-value DWI sequences were included during vCE training (p<.05). Non-significant effects (p>.05) were observed for the quantitative metrics on the full breast volume when comparing input combinations including T1w. Using T1w and DWI acquisitions during vCE training is necessary to achieve high satisfaction with contrast/SNR and good conspicuity of the enhancing findings. The input combination of T1w, T2w, and DWI sequences with three b-values showed the best qualitative performance.

Conclusion

vCE breast MRI performance is significantly influenced by input sequences. Quantitative metrics and visual quality of vCE images significantly benefit when a multi b-value DWI is added to morphologic T1w-/T2w-sequences as input for model training.

Key Results

The inclusion of diffusion-weighted imaging significantly improves the conspicuity of lesions/non-mass enhancements and satisfaction with the image contrast in virtual contrast-enhanced breast MRI.

The quality of virtual contrast-enhanced breast MRI scans benefits from the inclusion of high-resolution morphologic T1-weighted image acquisitions.

Quantitative metrics such as the structural similarity index and peak signal-to-noise ratio calculated over the entire breast volume insufficiently reflect variations in lesion/non-mass enhancement’s individual characteristics.
Barriers to sexual and reproductive health and rights of migrant and refugee youth: An exploratory socio-ecological qualitative analysis
Authors: Aibangbee Michaels , Micheal Sowbhagya , Liamputtong Pranee , Pithavadian Rashmi , Hossain Syeda Zakia , Mpofu Elias , Dune Tinashe
Published: May 2024

Purpose

Migrants and refugee youths’ (MRY) sexual and reproductive health and rights (SRHR) is a global health issue. MRY tend to encounter adverse SRH experiences because of their limited access to and knowledge of SRHR services. Using a socioecological framework, this study examined the barriers affecting MRY’s SRHR.

Methods

A cross-sectional study utilising a participatory action research design was used. 87 MRY (ages 16-26, from 20 different cultural groups living in Greater Western Sydney, Australia) participated in the study and completed seventeen focus group discussions on MRY’s experiences of SRHR. Focus groups were co-facilitated by youth project liaisons for authenticity and validity. The data were analysed thematically and interpreted using socioecological theory.

Results

The findings identified socioecological barriers such as lack of awareness and access to services, sociocultural dissonance, and under-implementation of SRHR services. These barriers include cultural disconnects, language barriers, remote service locations, intergenerational cultural conflicts, and ineffective SRHR services. Key themes included traditional and institutional stigma, lack of SRH education, reliance on social media for SRH information and privacy concerns.

Conclusion

There is limited consideration of MRY’s SRHR and the impact of intergenerational discordance and stigma on MRY’s rights. The findings suggest the necessity for a collaborative SRHR strategy and policy design that empowers MRY’s agency across multicultural contexts.
A general algorithm for consensus 3D cell segmentation from 2D segmented stacks
Authors: Zhou Felix Yuran , Yapp Clarence , Shang Zhiguo , Daetwyler Stephan , Marin Zach , Islam Md Torikul , Nanes Benjamin A , Jenkins Edward , Gihana Gabriel M , Chang Bo-Jui , Weems Andrew , Dustin Michael , Morrison Sean J , Fiolka Reto Paul , Dean Kevin M. , Jamieson Andrew , Sorger Peter Karl , Danuser Gaudenz Karl
Published: May 2024

Cell segmentation is the fundamental task. Only by segmenting, can we define the quantitative spatial unit for collecting measurements to draw biological conclusions. Deep learning has revolutionized 2D cell segmentation, enabling generalized solutions across cell types and imaging modalities. This has been driven by the ease of scaling up image acquisition, annotation and computation. However 3D cell segmentation, which requires dense annotation of 2D slices still poses significant challenges. Labelling every cell in every 2D slice is prohibitive. Moreover it is ambiguous, necessitating cross-referencing with other orthoviews. Lastly, there is limited ability to unambiguously record and visualize 1000s of annotated cells. Here we develop a theory and toolbox, u-Segment3D for 2D-to-3D segmentation, compatible with any 2D segmentation method. Given optimal 2D segmentations, u-Segment3D generates the optimal 3D segmentation without data training, as demonstrated on 11 real life datasets, >70,000 cells, spanning single cells, cell aggregates and tissue.
In-depth mass-spectrometry reveals phospho-RAB12 as a blood biomarker of G2019S LRRK2-driven Parkinson’s
Authors: Cortés Adriana , Phung Toan K. , de Mena Lorena , Garrido Alicia , Infante Jon , Ruíz-Martínez Javier , Galmés-Ordinas Miquel À. , Glendinning Sophie , Pérez Jesica , Roig Ana , Soto Marta , Cosgaya Marina , Ravasi Valeria , Fernández Manel , Rubiano-Castro Alejandro , Díaz Ramón , Hernández-Eguiazu Haizea , Sánchez-Quintana Coro , Vinagre-Aragón Ana , Mondragón Elisabet , Croitoru Ioana , Rivera-Sánchez María , Corrales-Pardo Andrea , Sierra María , Tolosa Eduardo , Malagelada Cristina , Nirujogi Raja S. , Fernández-Irigoyen Joaquín , Santamaría Enrique , Alessi Dario R. , Martí María J. , Ezquerra Mario , Fernández-Santiago Rubén
Published: May 2024

Leucine-rich repeat kinase 2 (LRRK2) inhibition is a promising disease-modifying therapy for LRRK2-associated Parkinson’s disease (L2PD) and idiopathic PD (iPD). Yet, pharmaco-dynamic readouts and progression biomarkers for disease modification clinical trials are insufficient. Employing phospho-/proteomic analyses we assessed the impact that LRRK2 activating mutations had in peripheral blood mononuclear cells (PBMCs) from a LRRK2 clinical cohort from Spain (n=174) encompassing G2019S L2PD patients (n=37), non-manifesting LRRK2 mutation carriers of G2019S, here, G2019S L2NMCs (n=27), R1441G L2PD patients (n=14), R1441G L2NMCs (n=11), iPD (n=40), and controls (n=45). We identified 207 differential proteins in G2019S L2PD compared to controls (39 up/ 168 down) and 67 in G2019S L2NMCs (10 up/ 57 down). G2019S down-regulated proteins affected the endolysosomal pathway, proteostasis and mitochondria, e.g., ATIC, RAB9A, or LAMP1. At the phospho-proteome level, we observed increases in endogenous phosphorylation levels of pSer106 RAB12 in G2019S carriers, which were validated by immunoblotting after 1 year of follow-up (n=48). Freshly collected PBMCs from 3 G2019S L2PD, 1 R1441G L2PD, 1 iPD, and 5 controls (n=10) showed strong diminishment of pSer106 RAB12 phosphorylation levels after in-vitro administration of the MLi-2 LRRK2 inhibitor. Using machine learning, we identified an 18-feature G2019S phospho-/protein signature capable of discriminating G2019S L2PD, L2NMCs, and controls with 96% accuracy that correlated with disease severity, i.e., UPDRS-III motor scoring. Our study identified pSer106 RAB12 as an endogenous biomarker in easily accessible PBMCs from G2019S carriers and suggests that phospho-/proteomic findings in human PBMCs such as pSer106 RAB12 can be deployed as a universal pharmaco-dynamic readout for L2PD, L2NMCs, and iPD. Future work may determine whether pSer106 RAB12 could help with patient enrichment and monitoring drug efficacy in LRRK2 clinical trials.
Sensitive detection of copy number alterations in samples with low circulating tumor DNA fraction
Authors: Mayrhofer Markus , Bergström Rebecka , Chellappa Venkatesh , Kotsalaynen Anastassija , Murugan Sarath , Crippa Alessio , De Laere Bram , Urtishak Karen , Sorensen Karina Dalsgaard , Garg Kavita , Singh Usha , Eklund Martin , Grönberg Henrik , Lindberg Johan
Published: May 2024

Copy number analysis is an important aspect of cancer genomics that enables identification of activated oncogenes, inactivated tumor suppressor genes and genome-wide signatures such as homologous recombination deficiency and the tandem duplication phenotype. Despite continuous development of copy number algorithms, the current sensitivity to detect clinically relevant focal alterations is poor if the cancer DNA fraction is low. This is particularly challenging for analysis of circulating tumor DNA (ctDNA) as it is not possible to know the cancer DNA fraction in advance or, as for tissue, macrodissect to increase the cancer DNA fraction. Here, we combine a novel algorithm (Jumble) with a tailored gene panel design and selected reference samples that achieve sensitive and highly specific detection of clinically relevant copy number alterations with limits of detection at 1-2% ctDNA fraction for amplifications and 4-8% for homozygous deletions. Jumble lowers the ctDNA fraction required for detection of homozygous deletions 3-6 times compared to commercial alternatives. Jumble is freely available as an R script and container, ready for integration into bioinformatic pipelines.
A Study of a Stochastic Model and Extinction Phenomenon of Meningitis Epidemic
Authors: Yaga S.J. , Saporu F.W.O.
Published: May 2024

A stochastic version of the deterministic model for meningitis epidemic by Yaga and Saporu (2024) is developed. The stochastic mean system of equations for possible state of an individual in the model and the extinction probabilities for carrier and infective are derived. Comparison of the system of stochastic mean equations and its deterministic analogue of profiles for the various compartments and the case-carrier trajectories show similar pattern with a time shift difference. This indicates that there must be caution in using the deterministic analogue as an approximating system of the stochastic mean equations for inferential purpose. Simulation studies of the comparison of the compartmental profiles for the general case; model I, with the assumption that a proportion (φ ≠0), of the infected susceptible can move directly to the infective stage and that of the special case, model II, whenφ= 0 is examined for various values ofϵ(odds in favour of a carrier transmitting infection)≤2. It is only whenϵ= 2 that model II can approximate model I in all compartments except that of the carrier. Transmission rate,β, loss of carriership rate,σandϵare identified as the most sensitive parameters of the extinction probabilities. Threshold results derived for carrier and infective extinction probabilities are distinct but bear some relation, transmission rate required for carrier extinction is square of that for infective. It is concluded that carriership play a more prominent role in the transmission of meningitis epidemic and efforts aimed at control should be targeted at reducing the transmission rate and increasing the loss of carriership.