bluuebunny/crossref_metadata_2025 huggingface dataset:
Hierarchies of stratigraphic discontinuity surfaces in siliciclastic, carbonate and mixed siliciclastic‐bioclastic tidalites: Implications for fluid migration in reservoir quality assessment
Authors: Chiarella Domenico , Longhitano Sergio G. , Spalluto Luigi , Martinius Allard W.
Published: August 2024

The hierarchies of the stratigraphic discontinuity surfaces observed in ancient tidalites are qualitatively assessed, aiming to evaluate their role as possible preferential conduits for fluid migration. Three outcrop examples are presented from microtidal settings of southern Italy: (i) siliciclastic tidalites consisting of quartz‐rich cross‐stratified sandstones generated by strong two‐directional tidal currents flowing along a tidal strait; (ii) carbonate tidalites, which accumulated in a Cretaceous lagoon and tidal flat where peritidal cycles formed vertically‐stacked sequences of biopeloidal and fenestral packstones, wackestones and bindstones during repeated phases of Milankovitch‐scale sea‐level changes; (iii) mixed, siliciclastic‐bioclastic tidalites, deposited in a bay and recording offshore‐transition, to shoreface wave‐dominated and tide‐influenced environments. Observations made during this study suggest that fluid movement can be controlled by the presence of main bounding surfaces that occur at different dimensions, from large (hectometre)‐scale, to medium (decametre)‐scale, to smaller (metre)‐scales. These surfaces produced either by depositional or erosional processes, are characterised by different features and geometries in siliciclastic, carbonate and mixed siliciclastic‐bioclastic tidalites arguably revealing complex internal pathways for fluid flows. These results suggest that fluids propagating along the main discontinuities follow a dominant sub‐horizontal direction of propagation, associated with minor sub‐vertical movements, due to local internal surface geometries and interconnections and a general lack of fractures. This surface‐based approach to the study of fluid‐flow transmission within stratified rocks represents a conceptual attempt to predict fluid mobility and reservoir potential in tidalite‐bearing siliciclastic, carbonate and mixed reservoir rocks.
Expression and Transcriptional Targets of TGFβ‐RII in Paracentrotus lividus Larval Skeletogenesis
Authors: Goloe Daniel , Gildor Tsvia , Ben‐Tabou de‐Leon Smadar
Published: August 2024

Organisms from the five kingdoms of life use minerals to harden their tissues and make teeth, shells and skeletons, in the process of biomineralization. The sea urchin larval skeleton is an excellent system to study the biological regulation of biomineralization and its evolution. The gene regulatory network (GRN) that controls sea urchin skeletogenesis is known in great details and shows similarity to the GRN that controls vertebrates' vascularization while it is quite distinct from the GRN that drives vertebrates' bone formation. Yet, transforming growth factor beta (TGF‐β) signaling regulates both sea urchin and vertebrates' skeletogenesis. Here, we study the upstream regulation and identify transcriptional targets of TGF‐β in the Mediterranean Sea urchin species, Paracentrotus lividus. TGF‐βRII is transiently active in the skeletogenic cells downstream of vascular endothelial growth factor (VEGF) signaling, in P. lividus. Continuous perturbation of TGF‐βRII activity significantly impairs skeletal elongation and the expression of key skeletogenic genes. Perturbation of TGF‐βRII after skeletal initiation leads to a delay in skeletal elongation and minor changes in gene expression. TGF‐β targets are distinct from its transcriptional targets during vertebrates' bone formation, suggesting that the role of TGF‐β in biomineralization in these two phyla results from convergent evolution.
Generation of an Armcx1 Conditional Knockout Mouse
Authors: Bright Cora L. , Bomze Howard M. , Bhaumik Mantu , Kay Jeremy N. , Cartoni Romain , Gospe Sidney M.
Published: August 2024

Armadillo repeat‐containing X‐linked protein‐1 (Armcx1) is a poorly characterized transmembrane protein that regulates mitochondrial transport in neurons. Its overexpression has been shown to induce neurite outgrowth in embryonic neurons and to promote retinal ganglion cell (RGC) survival and axonal regrowth in a mouse optic nerve crush model. In order to evaluate the functions of endogenous Armcx1 in vivo, we have created a conditional Armcx1 knockout mouse line in which the entire coding region of the Armcx1 gene is flanked by loxP sites. This Armcx1fl line was crossed with mouse strains in which Cre recombinase expression is driven by the promoters for β‐actin and Six3, in order to achieve deletion of Armcx1 globally and in retinal neurons, respectively. Having confirmed deletion of the gene, we proceeded to characterize the abundance and morphology of RGCs in Armcx1 knockout mice aged to 15 months. Under normal physiological conditions, no evidence of aberrant retinal or optic nerve development or RGC degeneration was observed in these mice. The Armcx1fl mouse should be valuable for future studies investigating mitochondrial morphology and transport in the absence of Armcx1 and in determining the susceptibility of Armcx1‐deficient neurons to degeneration in the setting of additional heritable or environmental stressors.
Increasing inter‐word spacing reduces migration errors and improves reading comprehension in students with dyslexia
Authors: Price‐Mohr Ruth Maria , Bernard Price Colin
Published: August 2024

We report a small study in which we explored the effects of manipulating narrative text on levels of comprehension for students with and without dyslexia. Using two pieces of standardised narrative text deemed to be of similar difficulty and length, we manipulated the texts such that we could present two texts to each participant, one in each condition. The first condition was text using standard inter‐word spacing; the second condition used increased inter‐word spacing. Scores on standardised comprehension questions were significantly improved for participants with dyslexia. Additionally, given that there is evidence of delayed visual attention disengagement in individuals with specific forms of dyslexia, we hypothesised that the phenomena of migration of letters and words for some readers might be mitigated by increasing inter‐word spacing. We did indeed find that incidence of migration was significantly reduced in this condition for all participants.
Size‐dependent effects of dams on river ecosystems and implications for dam removal outcomes
Authors: Brown Rebecca L. , Charles Don , Horwitz Richard J. , Pizzuto James E. , Skalak Katherine , Velinsky David J. , Hart David D.
Published: August 2024

Understanding the relationship between a dam's size and its ecological effects is important for prioritization of river restoration efforts based on dam removal. Although much is known about the effects of large storage dams, this information may not be applicable to small dams, which represent the vast majority of dams being considered for removal. To better understand how dam effects vary with size, we conducted a multidisciplinary study of the downstream effect of dams on a range of ecological characteristics including geomorphology, water chemistry, periphyton, riparian vegetation, benthic macroinvertebrates, and fish. We related dam size variables to the downstream–upstream fractional difference in measured ecological characteristics for 16 dams in the mid‐Atlantic region ranging from 0.9 to 57 m high, with hydraulic residence times (HRTs) ranging from 30 min to 1.5 years. For a range of physical attributes, larger dams had larger effects. For example, the water surface width below dams was greater below large dams. By contrast, there was no effect of dam size on sediment grain size, though the fraction of fine‐grained bed material was lower below dams independently of dam size. Larger dams tended to reduce water quality more, with decreased downstream dissolved oxygen and increased temperature. Larger dams decreased inorganic nutrients (N, P, Si), but increased particulate nutrients (N, P) in downstream reaches. Aquatic organisms tended to have greater dissimilarity in species composition below larger dams (for fish and periphyton), lower taxonomic diversity (for macroinvertebrates), and greater pollution tolerance (for periphyton and macroinvertebrates). Plants responded differently below large and small dams, with fewer invasive species below large dams, but more below small dams. Overall, these results demonstrate that larger dams have much greater impact on the ecosystem components we measured, and hence their removal has the greatest potential for restoring river ecosystems.
Daily Physical Activity Does Not Contribute to Differences in Muscle Oxidative Capacity Between Overweight and Obesity
Authors: Simon Abigayle B. , Derella Cassandra C. , Looney Jacob C. , Norland Kimberly , Wang Xiaoling , Harris Ryan A.
Published: August 2024

Background

The interaction between physical activity, skeletal muscle health, and adiposity has been explored in normal weight and overweight/obesity grouped together; however, the overall risks associated with being overweight are less than those observed with obesity and can be confounded by disparities in both sex and race. Thus, the present study sought to investigate the intricate interplay of daily physical activity and skeletal muscle oxidative capacity (SMOC) in overweight and obesity, while exploring how sex and race impact this dynamic relationship.

Methods

One hundred and forty participants were grouped by body mass index (BMI) as overweight (n = 73; BMI >25–<30 kg/m2) or obese (n = 67; BMI ≥30 kg/m2). SMOC was assessed using near‐infrared spectroscopy and daily physical activity was assessed for 7 days using accelerometry.

Results

Overweight individuals exhibited a higher (p = 0.004) SMOC and engaged in more (p = 0.007) vigorous physical activity compared to obese individuals. In addition, SMOC was lower (p = 0.005) in obese non‐Hispanic Black (NHB) men compared to overweight NHB men. No relationships between physical activity and SMOC were observed.

Conclusion

Physical activity is not associated with differences in SMOC in overweight and obesity. Obese individuals engage in less vigorous physical activity and exhibit lower SMOC compared to overweight individuals and these differences are emphasised in NHB men.
Copper(II) Complexes of Phenolate‐Bridged Dimeric Cyclam Ligands: Synthesis, Coordination and Electrochemical Study
Authors: Šrein Jakub , Koláčná Lucie , Kotek Jan , Kubíček Vojtěch , Ludvík Jiří
Published: August 2024

Bis(macrocyclic) complexes are investigated as artificial analogues of natural dinuclear metalloenzymes. Two ligands containing two cyclam rings connected through a p‐cresol or 4‐nitrophenol spacer were synthesized and their complexing properties were investigated. CuII complexes were prepared and their properties were studied by a combination of spectral, diffraction and electrochemical methods. The phenolate group is not or only weakly coordinated to the central CuII ion and the two macrocycles behave mostly as two independent complexing units. All the determined solid‐state structures showed cyclam adopting trans‐III geometry, however, solution study indicated the presence of more isomers in the solution whose abundance changes with pH. Electrochemical reduction of the complexes is irreversible and results in the reductive decomplexation to amalgamated Cu metal. The amalgamated metal is re‐oxidized to CuII during the anodic scan of CV and the metal ion is re‐coordinated. The ligand containing the nitro group shows an irreversible four‐electron reduction of the nitro group. The ligands and the complexes undergo also a slow degradation when incubated in the aqueous solutions for a prolonged time. The degradation relies on the “retro‐Mannich” cleavage of the methylene bridge connecting the cyclam ring with the phenol moiety.
Exploring the Stability of Primary Phosphine Oxides: Correlation with Primary Phosphine′s Air‐Stability?
Authors: Horký Filip , Bruhn Clemens , Pietschnig Rudolf
Published: August 2024

To better understand the stability of isolable primary phosphine oxides, new members of this family were synthesized through the oxidation of the corresponding phosphines. Specifically, the previously reported air‐stable primary phosphines (R)‐2‐phosphanyl‐2’‐methoxy‐1,1’‐binaphthyl, 9,10‐dihydro‐9,10‐etheno‐anthracen‐9‐yl phosphine, and 3‐phosphino‐2‐naphthol were treated with hydrogen peroxide or meta‐chloroperoxybenzoic acid to yield the new primary phosphine oxides. The compounds were characterized using NMR, MS, EA, and X‐ray crystallography. The oxides were further investigated in thermal disproportionation, and studied as ligands in half‐sandwich Ru(II) complexes bearing an auxiliary η6‐p‐cymene ligand.
Visible‐Light Induced and PIFA Enabled [4+2] Annulation of Alkenes with N‐Aryl Substituted Hydroxamic Acids
Authors: Wang Yu‐Zhao , Jiang Menglu , Zhang Feng , Zhang Hua‐Wei , Wu Yue , Yu Wei , Li Yan
Published: August 2024

In this paper, we reported a facile approach for the preparation of benzo[c][1,2]oxazine scaffolds via visible light induced phenyl iodine bis(trifluoroacetate) (PIFA) oxidative [4+2] annulation of vinyl benzenes with N‐aryl substituted hydroxamic acids. In the transformation, amidoxyl radicals are readily generated via covalent I−O bond formation and photo‐induced I−O cleavage from N‐aryl substituted hydroxamic acids, and their coupling with vinyl arenes in the form of [4+2] annulation delivers benzo[c]‐[1,2]oxazines derivatives. This reaction proceeds in the absence of transition metals and catalysts, exhibiting broad substrate scope of both alkenes and N‐aryl substituted hydroxamic acids.
The thickness of the retinal nerve fiber layer, macula, and ganglion cell‐inner plexiform layer in people with drug‐resistant epilepsy
Authors: Chen Yujie , Xiong Weixi , Lu Lu , Wu Xintong , Cao Le , Chen Jiani , Xiao Yingfeng , Sander Josemir W. , Wu Bo , Zhou Dong
Published: August 2024

Objective

Using Optical coherence tomography (OCT), we evaluated the association between peripapillary retinal nerve fiber, macular thickness, macular ganglion cell‐inner plexiform layer, and drug resistance.

Methods

In this cross‐sectional study, we recruited people diagnosed with epilepsy and healthy controls. People with epilepsy were further stratified as drug‐resistant or non‐drug‐resistant based on their response to anti‐seizure medications. OCT measurements were conducted, and findings in right eye were analyzed.

Results

Fifty‐one drug‐resistant participants, 37 non‐drug‐resistant, and 45 controls were enrolled. The average peripapillary retinal nerve fiber layer, ganglion cell‐inner plexiform layer, and macular thickness were thinner in the epilepsy groups than in controls. The drug‐resistant group had significantly lower average ganglion cell‐inner plexiform layer thickness (p = 0.004) and a higher proportion of abnormal/borderline GC/IPL thickness (p = 5.40E‐04) than the non‐drug‐resistant group. Nevertheless, no significant differences were seen between the average thickness of peripapillary retinal nerve fiber and macular thickness. The temporal sectors of these three parameters were also significantly thinner in the drug‐resistant group than in the non‐drug‐resistant. In a multivariate regression model, drug resistance was an independent predictor of reduced ganglion cell‐inner plexiform thickness (Odds ratios OR = 10.25, 95% CI 2.82 to 37.28). Increased seizure frequency (r = −0.23, p = 0.039) and a higher number of anti‐seizure medications ever used (r = −0.27, p = 0.013) were negatively associated with ganglion cell‐inner plexiform layer thickness.

Significance

Individuals with drug‐resistant epilepsy had a consistent reduction in average ganglion cell‐inner plexiform layer thickness and the temporal sector of peripapillary retinal nerve fiber layer and macular thickness. This suggests that ganglion cell‐inner plexiform layer thickness could potentially serve as an indicator of the burden of drug resistance, as it correlated with reduced thickness in individuals having more frequent seizures and greater exposure to ASMs.

Plain Language Summary

In our study, we used a special tool called OCT to measure how thick the retina is in people with epilepsy and in healthy control. We found that the retina was consistently thinner in all areas for those with epilepsy compared to healthy control. Particularly, a specific layer called the ganglion cell‐inner plexiform layer was a lot thinner in the group that didn't respond to medications, and this thinning was related to how often seizures occurred and how much medications were taken. Also, certain parts of the retina were thinner in the drug‐resistant group.
Clinical and genetic analysis of 23 Chinese children with epilepsy associated with KCNQ2 gene mutations
Authors: Yu Xixi , Che Fengyuan , Zhang Xin , Yang Li , Zhu Liping , Xu Na , Qiu Shiyan , Li Yufen
Published: August 2024

Objective

To summarize the clinical features and genetic mutation characteristics of Chinese children with KCNQ2‐related epilepsy.

Methods

A cohort of children with genetically caused epilepsy was evaluated at Linyi People's Hospital from January 2017 to December 2023. After next‐generation sequencing and pathogenicity analysis, we summarized the medical records and genetic testing data of the children who had KCNQ2 gene mutations.

Results

We identified 23 KCNQ2 gene mutations. 73.9% (n = 17) of the mutation sites were located in S5–S6 segments and the C‐terminal region. In addition to the common phenotypes, 2 new phenotypes were identified: infantile convulsion with paroxysmal choreoathetosis (ICCA) and febrile seizure plus (FS+). Of all the cases with abnormal video‐electro‐encephalography, three cases with self‐limited familial infantile epilepsy (SeLNE) exhibited a small number of multifocal discharges. Of the patients who have taken a particular antiepileptic drug, the statistics on the number of patients who have responded to the drug are as follows: oxcarbazepine (8/9, 88.9%), levetiracetam (5/7, 71.4%), phenobarbital (9/16, 56.3%), and topiramate (2/5, 40.0%). However, the efficacy of phenobarbital varied widely in treating SeLNE and KCNQ2‐DEE. At the final follow‐up, 1 case with SeLNE had a transient developmental regression and 7 cases with KCNQ2‐DEE had mild to severe developmental backwardness.

Significance

Although clinically rare, we report 10 new KCNQ2 mutations and two new phenotypes: ICCA and FS+. This further expands genetic and phenotypic spectrum of KCNQ2‐related epilepsy. The gene mutation sites are mostly located in S5–S6 segments and the C‐terminal region, and the former is usually associated with KCNQ2‐DEE. Sodium channel blockers (including oxcarbazepine and topiramate) and levetiracetam should be prioritized over phenobarbital for KCNQ2‐DEE. Some cases with KCNQ2‐related epilepsy may have transient developmental regression during periods of frequent seizures. Early treatment and early seizure control may be beneficial for willing outcomes in children with KCNQ2‐DEE.

Plain Language Summary

This article reports 23 cases of children with KCNQ2‐related epilepsy, including 10 new mutation sites and 2 new phenotypes. It further expands the genetic and phenotypic spectrum of KCNQ2‐related epilepsy. In addition, the article summarizes the gene mutation characteristics and clinical manifestations of children with KCNQ2‐related epilepsy, with the expectation of providing a certain theoretical basis for the diagnosis and treatment of such patients.
Encouraging, empowering, and educating: Informal educators, caregivers, and children as partners in computational thinking activities
Authors: Campana Kathleen , Mills J. Elizabeth , Chun Jeeyeon , Ickes Jessica
Published: August 2024

Informal learning environments, such as libraries and museums, are key areas for supporting computational thinking (CT) with young children and their families. Educators in these environments are working to offer CT‐related experiences and activities for families of young children, often incorporating aspects of sociocultural learning such as scaffolding and dialogic practices. Because the parent/caregiver is typically present with their young child in these environments, there is an opportunity to provide them with CT information and support so that they can then actively engage in and encourage their child's CT learning, thereby extending their child's capabilities in a zone of proximal development. Previous research by Ohland et al. offers an initial framework of parental roles in CT experiences that serves as a foundation for this study's analysis of interviews with 18 libraries and museums from across the United States. The goal was to understand informal educators' goals for caregiver participation in CT activities with young children and their strategies for enabling caregivers to embody these different roles. Findings reveal that educators want caregivers to play a variety of roles with their child(ren) in these CT experiences. Furthermore, educators are implementing a variety of methods that explicitly encourage interaction, collaboration, and more. The connections between these goals and methods begin to build a model of caregiver encouragement, empowerment, and education in CT experiences in informal learning environments.
Development of healthier gummy candy by substituting glucose syrup with various fruit juice concentrates
Authors: Pekdogan Goztok Serpil , Habibzadeh Khiabani Arezou , Toker Omer Said , Palabiyik Ibrahim , Konar Nevzat
Published: August 2024

The main objective of this study was to evaluate the effects of various formulations of fruit juice concentrates (pomegranate, grape, and sour cherry) on the pH, water activity, density, color, texture, and microstructure characteristics of candies instead of glucose syrup. The experimental points of the study were examined by a D‐optimal mixture design to optimize the concentration of fruits used in the formulation and achieve excellent physicochemical characteristics. Fruit juice concentrates, either singly or in combination, were used as a complete substitute for glucose syrup in the formulation. Total fruit juice concentration used in the formulation was 54.07% and each of the fruit juice concentrations changed between 0 and 54.07% in the formulation. By combining these three fruit juices, 14 gummy candy samples were produced, depending on the Special cubic, cubic, and quadratic models that were used for the effects on the physicochemical properties (pH, water activity, density, L*, a*, b*, and chroma), and the texture profile analysis (TPA) (hardness, cohesiveness, springiness, and resilience) parameters according to independent variables. Results showed that pH, water activity, and density values of the gummy candy samples were found to be in the range of 2.22–3.08, 0.46–0.52, and 1.10–1.53 g/mL, respectively, and were significantly affected by different fruit juice concentrates (p < .05). The texture profile analysis showed that except for springiness, fruit juice concentrations significantly affected the texture profile (p < .05). The texture values, such as hardness, springiness, cohesiveness, gumminess, and resilience of the gummy candy samples, were determined as 146.1–938.8 N, 0.63–0.99, 0.75–1.19, 136.02–947.94 g, and 0.12–0.51, respectively. In addition, various fruit juice concentrates significantly affected the color parameters of gummy candies, and using pomegranate juice and sour cherry concentrates increased the +a* value of the gummy candies. Therefore, fruit juice‐based gummy candies can be developed as value‐added gummy candies by using fruit juice concentrates.
The prevalence of depression in women with pregnancy‐related pelvic girdle pain: A systematic review and meta‐analysis
Authors: Halliday Bradley , Chatfield Sarah , Hosking Joanne , Freeman Jennifer
Published: August 2024

Background and Aims

Pregnancy‐related pelvic girdle pain (PPGP) is estimated to affect between 20% and 70% of pregnant women with 10% experiencing it for more than 3 months postpartum. Women may also experience depression during this period. Understanding the prevalence of depression in women with PPGP is important to inform clinical management. This systematic review aimed to examine the prevalence of depression in women with PPGP in the antepartum and postpartum periods.

Methods

A systematic review and meta‐analysis. Seven databases were searched from inception until May 24, 2023, combining keywords relating to pelvic girdle pain (PGP), depression, and pregnancy. Two investigators independently screened study titles and abstracts against the eligibility criteria, extracting data characteristics of all included studies. Included articles were assessed for risk of bias. Summary estimates of the prevalence of depression were calculated with a random effects meta‐analysis (stratified by antepartum and postpartum periods).

Results

Eleven studies (3172 participants) were included with nine suitable for meta‐analysis. The overall summary estimate of prevalence of depression among women with PPGP was 24% (95% confidence interval [CI] = 15%–37%), with significant heterogeneity between studies (I2 = 97%, p < 0.01). Among individual studies, the estimates ranged from 18% to 48% in the antepartum PGP population and from 5% to 39% in the postpartum PGP population. The summary estimate in the antepartum group was 37% (95% CI = 19%–59%; prediction interval 8%–81%) and 15% (95% CI = 7%–30%; prediction interval 3%–56%) in the postpartum group, although time (antepartum vs. postpartum) did not have a statistically significant moderating effect (p = 0.06). Two thirds of the studies were undertaken with Scandinavian populations, limiting the generalizability of these findings.

Conclusion

Summary estimates for the prevalence of depression in women with PPGP are similar to previous studies investigating depression in the general peri‐natal population.
Hair follicle punch grafts in hard‐to‐heal wounds: A monocenter study and patient survey
Authors: Jansen Theresa M. , Janßen Sarah , Bölke Edwin , Homey Bernhard , Hoff Norman‐Philipp
Published: August 2024

Background and Aims

Chronic wounds present a growing challenge in the aging population, resulting in an extended course of treatment and an increased influx of patients with recalcitrant wounds seeking admission to hospitals. Furthermore, the general trend in patient care is toward simple and inexpensive treatment methods, feasible in an outpatient setting with little material costs. This retrospective case study aims to elucidate the operative procedure and outcomes associated with hair follicle unit transplantation utilizing punch grafts from the scalp for the management of hard‐to‐heal wounds.

Methods

A cohort of 28 patients, comprising 20 males and eight females, with a mean age of 72.61 years (range: 48−89) and an average wound area of 82.49 cm2, underwent dissection of punch grafts containing hair follicles (2−3 mm in diameter) from the scalp. Subsequently, these grafts were transplanted into the wound bed. The retrospective evaluation of ulcer healing encompassed photo documentation and clinical records, while patient satisfaction was assessed through structured questionnaires.

Results

In 78.6% (22) of the cases, a favorable impact on wound healing was observed, characterized by epithelization, and in 57.1% (16) of the patients, complete wound closure was achieved. With the exception of one donor site, all other sites healed without complications. The patient survey indicated that the majority of individuals subjected to the procedure did not perceive it as painful or time‐consuming. Notably, 81% (17) of individuals expressed a willingness to undergo the treatment again. Even in challenging wound conditions, such as pyoderma gangrenosum, our method demonstrated a positive effect on wound healing.

Conclusion

Within our cohort, the utilization of hair follicle units in the management of hard‐to‐heal wounds resulted in either complete or partial wound closure for the majority of patients, accompanied by minimal morbidity, reduced operation time, and a low incidence of complications and associated costs.
Neuroscience of cancer: Research progress and emerging of the field
Authors: AbuQeis Issam , Zou Yu , Ba Ying‐Chun , Teeti Abeer A.
Published: August 2024

Cancer cells immediately expand and penetrate adjoining tissues, as opposed to metastasis, that is the spread of cancer cells through the circulatory or lymphatic systems to more distant places via the invasion process. We found that a lack of studies discussed tumor development with the nervous system, by the aspects of cancer‐tissue invasion (biological) and chemical modulation of growth that cascades by releasing neural‐related factors from the nerve endings via chemical substances known as neurotransmitters. In this review, we aimed to carefully demonstrate and describe the cancer invasion and interaction with the nervous system, as well as reveal the research progress and the emerging neuroscience of cancer. An initial set of 160 references underwent systematic review and summarization. Through a meticulous screening process, these data were refined, ultimately leading to the inclusion of 98 studies that adhered to predetermined criteria. The outcomes show that one formidable challenge in the realm of cancer lies in its intrinsic heterogeneity and remarkable capacity for rapid adaptation. Despite advancements in genomics and precision medicine, there is still a need to identify new molecular targets. Considering cancer within its molecular and cellular environment, including neural components, is crucial for addressing this challenge. In conclusion, this review provides good referential data for direct, indirect, biological, and chemical interaction for nerve tissue–tumor interaction, suggesting the establishment of new therapy techniques and mechanisms by controlling and modifying neuron networks that supply signals to tumors.
Improving the clinical meaning of surrogate endpoints: An empirical assessment of clinical progression in phase III oncology trials
Authors: Sherry Alexander D. , Lin Timothy A. , McCaw Zachary R. , Beck Esther J. , Kouzy Ramez , Abi Jaoude Joseph , Passy Adina H. , Miller Avital M. , Kupferman Gabrielle S. , Fuller Clifton David , Thomas Charles R. , Koay Eugene J. , Tang Chad , Msaouel Pavlos , Ludmir Ethan B.
Published: August 2024

Disease progression in clinical trials is commonly defined by radiologic measures. However, clinical progression may be more meaningful to patients, may occur even when radiologic criteria for progression are not met, and often requires a change in therapy in clinical practice. The objective of this study was to determine the utilization of clinical progression criteria within progression‐based trial endpoints among phase III trials testing systemic therapies for metastatic solid tumors. The primary manuscripts and protocols of phase III trials were reviewed for whether clinical events, such as refractory pain, tumor bleeding, or neurologic compromise, could constitute a progression event. Univariable logistic regression computed odds ratios (OR) and 95% CI for associations between trial‐level covariates and clinical progression. A total of 216 trials enrolling 148,190 patients were included, with publication dates from 2006 through 2020. A major change in clinical status was included in the progression criteria of 13% of trials (n = 27), most commonly as a secondary endpoint (n = 22). Only 59% of trials (n = 16) reported distinct clinical progression outcomes that constituted the composite surrogate endpoint. Compared with other disease sites, genitourinary trials were more likely to include clinical progression definitions (16/33 [48%] vs. 11/183 [6%]; OR, 14.72; 95% CI, 5.99 to 37.84; p < .0001). While major tumor‐related clinical events were seldom considered as disease progression events, increased attention to clinical progression may improve the meaningfulness and clinical applicability of surrogate endpoints for patients with metastatic solid tumors.
Self‐collected versus clinician‐collected anal swabs for anal cancer screening: A systematic review and meta‐analysis
Authors: Dyer Clare E. F. , Jin Fengyi , Hillman Richard J. , Nyitray Alan G. , Roberts Jennifer M. , Law Carmella , Grulich Andrew E. , Poynten I. Mary
Published: August 2024

Anal squamous cell carcinoma (ASCC) incidence is increasing globally. International consensus guidelines published in 2024 include HPV and/or cytology testing of anal swabs in those at greatest risk of ASCC. Self‐collected anal swabs may be important for increasing screening uptake, but evidence is needed as to their equivalence to clinician‐collected swabs. We searched Medline, Embase, Cochrane Library, and CINAHL databases for publications to 13 June 2023. Studies were included if reporting data on HPV testing, cytology testing, or acceptability, for both self‐ and clinician‐collected anal swabs. Risk of bias was assessed using the QUADAS‐2 assessment tool. The primary outcome was HPV and cytology sampling adequacy. Secondary outcomes were HPV and cytology results, and acceptability of collection methods. Thirteen papers describing 10 studies were eligible. Sample adequacy was comparable between self‐ and clinician‐collected swabs for HPV testing (meta‐adequacy ratio: 1.01 [95% CI 0.97–1.05]) but slightly lower for cytology by self‐collection (meta‐adequacy ratio: 0.91 [95% CI 0.88–0.95]). There was no significant difference in prevalence (meta‐prevalence ratio: 0.83 (95% CI 0.65–1.07) for any HR‐HPV, 0.98 (95% CI 0.84–1.14) for any HPV, and 0.68 (95% CI 0.33–1.37) for HPV16), or any cytological abnormality (meta‐prevalence ratio 1.01 [95% CI 0.86–1.18]). Only three papers reported acceptability results. Findings indicate self‐collection gives equivalent sample adequacy for HPV testing and ~ 10% inferior adequacy for cytological testing. Meta‐prevalence was similar for HPV and cytology, but confidence intervals were wide. Larger studies are required to definitively assess use of self‐collected swabs in anal cancer screening programs, including acceptability.
The impact of new millennium crises on the power of Islamic banks in deposit markets
Authors: Alhalboni Maryam , Baldwin Kenneth
Published: August 2024

We investigate the impact of three crises on the power of Islamic banks in deposit markets: the Global Financial Crisis, 2007–2009 (GFC), the Arab Spring political crisis, 2011–2013, and the COVID‐19 health crisis, 2020–2022. Applying difference‐in‐difference (DID) and GMM techniques to panel data for 2004–2022, we find that the power of Islamic banks increased in countries most affected by the GFC, but only for oil‐exporters, as elevated oil prices inflated deposited liquidity. In contrast to the GFC, the market power of countries highly affected by the Arab Spring decreased as depositors withdrewen masse. For these countries, oil export status was irrelevant, and whilst government integrity is significant, it accounts for a small amount of heterogeneity in the country‐level cross‐section due to widely held public attitudes towards institutions during the crisis. For COVID‐19, the market power of Islamic banks initially increased at the outset of the pandemic due to a surge in precautionary deposits, but later decreased due to economic activity constraints. The stringency of lockdowns had little effect on market power in countries that suffered the highest COVID‐19 death rates. These and other findings specific to each crisis provide a rich array of private and public policy implications relevant to crises of different types for bank liquidity crisis management, financial conduct policies, and state‐backed lending stimulus packages.
Multiple‐dose pharmacokinetics of cenerimod and the effect of charcoal on its elimination
Authors: Mueller Markus S. , Juif Pierre‐Eric , Charfi Hakim , Dingemanse Jasper
Published: August 2024

Cenerimod is a sphingosine‐1‐phosphate receptor 1 modulator that reduces tissue availability of circulating lymphocytes. The compound is in Phase 3 development for the treatment of systemic lupus erythematosus. Its pharmacokinetic properties are characterized by slow absorption and multiphasic elimination with a long terminal half‐life (t½), potentially caused by enterohepatic circulation (EHC). In this trial in healthy participants, oral cenerimod 0.5 and 4 mg once daily was administered for 50 days, followed by oral administration of activated charcoal (ie, 50 mg every 12 h for 11 days, starting 24 h after the last cenerimod dose), to investigate the potential EHC of cenerimod and assess whether elimination of cenerimod can be accelerated. The multiple‐dose pharmacokinetics, pharmacodynamics, safety, and tolerability of cenerimod were also evaluated. For both doses, peak plasma concentrations were reached 6 and 7 h after dosing. Cenerimod accumulated approximately eightfold and (near) steady‐state conditions were reached after 50 doses, resembling clinically meaningful exposure to cenerimod. The t½ following 0.5 and 4 mg of cenerimod was 767 and 799 h (ie, 32 and 33 days) and 720 and 780 h (ie, 30 and 33 days) with or without administration of charcoal, respectively, indicating no statistically significant difference. Therefore, charcoal did not accelerate cenerimod elimination suggesting that there is no EHC of cenerimod. A reversible, dose‐dependent decrease in total lymphocyte count was observed. No safety concerns were identified; administration of charcoal was well tolerated.
Artificial intelligence‐assisted ultrasound‐guided regional anaesthesia: An explorative scoping review
Authors: Marino Martina , Hagh Rebecca , Hamrin Senorski Eric , Longo Umile Giuseppe , Oeding Jacob F. , Nellgard Bengt , Szell Anita , Samuelsson Kristian
Published: August 2024

Purpose

The present study reviews the available scientific literature on artificial intelligence (AI)‐assisted ultrasound‐guided regional anaesthesia (UGRA) and evaluates the reported intraprocedural parameters and postprocedural outcomes.

Methods

A literature search was performed on 19 September 2023, using the Medline, EMBASE, CINAHL, Cochrane Library and Google Scholar databases by experts in electronic searching. All study designs were considered with no restrictions regarding patient characteristics or cohort size. Outcomes assessed included the accuracy of AI‐model tracking, success at the first attempt, differences in outcomes between AI‐assisted and unassisted UGRA, operator feedback and case‐report data.

Results

A joint adaptive median binary pattern (JAMBP) has been applied to improve the tracking procedure, while a particle filter (PF) is involved in feature extraction. JAMBP combined with PF was most accurate on all images for landmark identification, with accuracy scores of 0.83, 0.93 and 0.93 on original, preprocessed and filtered images, respectively. Evaluation of first‐attempt success of spinal needle insertion revealed first‐attempt success in most patients. When comparing AI application versus UGRA alone, a significant statistical difference (p < 0.05) was found for correct block view, correct structure identification and decrease in mean injection time, needle track adjustments and bone encounters in favour of having AI assistance. Assessment of operator feedback revealed that expert and nonexpert operator feedback was overall positive.

Conclusion

AI appears promising to enhance UGRA as well as to positively influence operator training. AI application of UGRA may improve the identification of anatomical structures and provide guidance for needle placement, reducing the risk of complications and improving patient outcomes.

Level of Evidence

Level IV.
The ‘forgotten’ lateral patellofemoral ligament: The known unknown
Authors: Vasiliadis Angelo V. , Marín Fermín Theodorakys , Papakostas Emmanouil
Published: August 2024

The lateral patellofemoral ligament (LPFL) is an important anatomical structure and a stabilizer of the patella against medial subluxation or dislocation. It is located within the second layer of the lateral soft tissue of the knee, with firm attachments to the anterior‐distal region of the lateral femoral epicondyle and the the lateral edge of the patella and patellar tendon. LPFL has a non‐isometric character and decreases its length across the knee flexion, especially from 0° to 30°. Most LPFL injuries are iatrogenic (> 90%) and occur during lateral retinacular release, while the mainstay treatment option involves reconstruction of the torn ligament using an autograft or an allograft.
Contextual corporeality: Life in the ninth decade and beyond
Authors: Eliopoulos Elaine M. , Higgs Paul , Gilleard Chris
Published: August 2024

Increased longevity is occurring worldwide with the greatest increase in the numbers of the very old. Many gerontological scholars have noted that these changes pose a risk of exclusion of the very old whose ability to participate in society may be compromised by bodily challenges. While the growing number of people aged 80 years and over raises many issues concerning health and social care needs, demands for a skilled workforce, and scope for technical innovations designed to compensate for the infirmities of advanced old age, these topics tend to exclude consideration of the everyday experiences, interests and wishes of those in deep old age. The qualitative research reported here focuses on people in advanced old age and the associated corporeal challenges they may face, set in the context of living on the San Juan islands off the coast of Washington in the Pacific Northwest of the United States. The participants of this study were islanders ranging in age from 80 to 102 years with a median age of 83 (M = 85.9, SD = 5.95). A mixture of semistructured interview and a photo elicitation methodology was employed. The results of the study demonstrated that, while integral to daily life in deep old age, corporeal challenges per se did not necessarily lead to a sense of exclusion, at least in the context of island life. Thematic analysis of the findings suggested the importance of context in framing corporeality, and the need to look beyond objective indicators of disability and function to acknowledge the role of social belonging in ensuring the continuing citizenship and social engagement of people in their ninth decade and beyond.
Simultaneously implementing pathways for improving asthma, pneumonia, and bronchiolitis care for hospitalized children: Protocol for a hybrid effectiveness‐implementation, cluster‐randomized trial
Authors: Edwards Yeelen , Yang Nancy , Auerbach Andrew D. , Gonzales Ralph , McCulloch Charles E. , Howell Eric E. , Goldstein Jenna , Thompson Sara , Kaiser Sunitha V.
Published: August 2024

Background

Asthma, pneumonia, and bronchiolitis are the top causes of childhood hospitalization in the United States, leading to over 350,000 hospitalizations and ≈$2 billion in costs annually. The majority of these hospitalizations occur in general/community hospitals. Poor guideline adoption by clinicians contributes to poor health outcomes for children hospitalized with these illnesses, including longer recovery time/hospital stay, higher rates of intensive care unit transfer, and increased risk of hospital readmission. A prior single‐center study at a children's hospital tested a multicondition clinical pathway intervention (simultaneous implementation of multiple pathways for multiple pediatric conditions) and demonstrated improved clinician guideline adherence and patient health outcomes. This intervention has not yet been studied in community hospitals, which face unique implementation barriers.

Objective

To study the implementation and effectiveness of a multicondition pathway intervention for children hospitalized with asthma, pneumonia, or bronchiolitis in community hospitals.

Methods

We will conduct a pragmatic, hybrid effectiveness‐implementation, cluster‐randomized trial in community hospitals around the United States (1:1 randomization to intervention vs. wait‐list control). Our primary outcome will be the adoption of two to three evidence‐based practices for each condition over a sustained period of 2 years. Secondary outcomes include hospital length of stay, ICU transfer, and readmission.

Discussion

This hybrid trial will lead to a comprehensive understanding of how to pragmatically and sustainably implement a multicondition pathway intervention in community hospitals and an assessment of its effects. Enrollment began in July 2022 and is projected to be completed in September 2024. Primary analysis completion is anticipated in March 2025, with reporting of results following.
Computer‐Aided Classification of Breast Lesions Based on US RF Time Series Using a Novel Machine Learning Approach
Authors: Arab Mahsa , Fallah Ali , Rashidi Saeid , Dastjerdi Maryam Mehdizadeh , Ahmadinejad Nasrin
Published: August 2024

Objectives

One of the most promising adjuncts for screening breast cancer is ultrasound (US) radio‐frequency (RF) time series. It has the superiority of not requiring any supplementary equipment over other methods. This research aimed to propound a machine learning (ML) approach for automatically classifying benign, probably benign, suspicious, and malignant breast lesions based on the features extracted from the accumulated US RF time series.

Methods

In this article, 220 data of the aforementioned categories, recorded from 118 patients, were analyzed. The dataset, named RFTSBU, was registered by a SuperSonic Imagine Aixplorer medical/research system equipped with a linear transducer. The regions of interest (ROIs) of the B‐mode images were manually selected by an expert radiologist before computing the suggested features. Regarding time, frequency, and time‐frequency domains, 291 various features were extracted from each ROI. Finally, the features were classified by a pioneering technique named the reference classification method (RCM). Furthermore, the Lee filter was applied to evaluate the effectiveness of reducing speckle noise on the outcomes.

Results

The accuracy of two‐class, three‐class, and four‐class classifications were respectively calculated 98.59 ± 0.71%, 98.13 ± 0.69%, and 96.10 ± 0.66% (considering 10 repetitions) while support vector machine (SVM) and K‐nearest neighbor (KNN) classifiers with 5‐fold cross‐validation were utilized.

Conclusions

This article represented the proposed approach, named CCRFML, to distinguish between breast lesions based on registered in vivo RF time series employing an ML framework. The proposed method's impressive level of classification accuracy attests to its capability of effectively assisting medical professionals in the noninvasive differentiation of breast lesions.
Successful treatment of recalcitrant follicular lichen planus (lichen planopilaris) with the topical JAK 1/2 inhibitor ruxolitinib
Authors: Fetter Tanja , Wilsmann‐Theis Dagmar , de Vos‐Hillebrand Luka , Novak Natalija , Wenzel Joerg
Published: August 2024

We report the successful treatment of a patient with refractory follicular lichen planus (LP) with topical ruxolitinib, a Janus kinase (JAK) 1/2 inhibitor, which resulted in significant improvement of lesional skin within 1 month of daily use.