bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifractal Analysis of Measures Arising from Random Substitutions
Authors: Mitchell Andrew , Rutar Alex
Published: February 2024

We study regularity properties of frequency measures arising from random substitutions, which are a generalisation of (deterministic) substitutions where the substituted image of each letter is chosen independently from a fixed finite set. In particular, for a natural class of such measures, we derive a closed-form analytic formula for the $$L^q$$

L
q

-spectrum and prove that the multifractal formalism holds. This provides an interesting new class of measures satisfying the multifractal formalism. More generally, we establish results concerning the $$L^q$$

L
q

-spectrum of a broad class of frequency measures. We introduce a new notion called the inflation word$$L^q$$

L
q

-spectrum of a random substitution and show that this coincides with the $$L^q$$

L
q

-spectrum of the corresponding frequency measure for all $$q \ge 0$$

q
≥
0

. As an application, we obtain closed-form formulas under separation conditions and recover known results for topological and measure theoretic entropy.
Phase-contrast magnetic resonance imaging of intracranial and extracranial blood flow in carotid near-occlusion
Authors: Holmgren Madelene , Henze Alexander , Wåhlin Anders , Eklund Anders , Fox Allan J. , Johansson Elias
Published: February 2024

Purpose

Compare extracranial internal carotid artery flow rates and intracranial collateral use between conventional ≥ 50% carotid stenosis and carotid near-occlusion, and between symptomatic and asymptomatic carotid near-occlusion.

Methods

We included patients with ≥ 50% carotid stenosis. Degree of stenosis was diagnosed on CTA. Mean blood flow rates were assessed with four-dimensional phase-contrast MRI.

Results

We included 110 patients of which 83% were symptomatic, and 38% had near-occlusion. Near-occlusions had lower mean internal carotid artery flow (70 ml/min) than conventional ≥ 50% stenoses (203 ml/min, P < .001). Definite use of ≥ 1 collateral was found in 83% (35/42) of near-occlusions and 10% (7/68) of conventional stenoses (P < .001). However, there were no differences in total cerebral blood flow (514 ml/min vs. 519 ml/min, P = .78) or ipsilateral hemispheric blood flow (234 vs. 227 ml/min, P = .52), between near-occlusions and conventional ≥ 50% stenoses, based on phase-contrast MRI flow rates. There were no differences in total cerebral or hemispheric blood flow, or collateral use, between symptomatic and asymptomatic near-occlusions.

Conclusion

Near-occlusions have lower internal carotid artery flow rates and more collateral use, but similar total cerebral blood flow and hemispheric blood flow, compared to conventional ≥ 50% carotid stenosis.
Outer membrane vesicles as a platform for the discovery of antibodies to bacterial pathogens
Authors: Lei Eric K. , Azmat Aruba , Henry Kevin A. , Hussack Greg
Published: February 2024

Bacterial outer membrane vesicles (OMVs) are nanosized spheroidal particles shed by gram-negative bacteria that contain biomolecules derived from the periplasmic space, the bacterial outer membrane, and possibly other compartments. OMVs can be purified from bacterial culture supernatants, and by genetically manipulating the bacterial cells that produce them, they can be engineered to harbor cargoes and/or display molecules of interest on their surfaces including antigens that are immunogenic in mammals. Since OMV bilayer-embedded components presumably maintain their native structures, OMVs may represent highly useful tools for generating antibodies to bacterial outer membrane targets. OMVs have historically been utilized as vaccines or vaccine constituents. Antibodies that target bacterial surfaces are increasingly being explored as antimicrobial agents either in unmodified form or as targeting moieties for bactericidal compounds. Here, we review the properties of OMVs, their use as immunogens, and their ability to elicit antibody responses against bacterial antigens. We highlight antigens from bacterial pathogens that have been successfully targeted using antibodies derived from OMV-based immunization and describe opportunities and limitations for OMVs as a platform for antimicrobial antibody development.

Key points

• Outer membrane vesicles (OMVs) of gram-negative bacteria bear cell-surface molecules

• OMV immunization allows rapid antibody (Ab) isolation to bacterial membrane targets

• Review and analysis of OMV-based immunogens for antimicrobial Ab development
Tailor-made solvents for microbial carotenoids recovery
Authors: Mussagy Cassamo U. , Hucke Henua U. , Ramos Nataly F. , Ribeiro Helena F. , Alves Mariana B. , Mustafa Ahmad , Pereira Jorge F. B. , Farias Fabiane O.
Published: February 2024

In recent years, microbial carotenoids have emerged as a promising alternative for the pharmaceutical and food industries, particularly in promoting human health due to their potent antioxidant and antimicrobial properties. Microbial carotenoids, particularly those produced by yeast, bacteria, and microalgae, are synthesized intracellularly, requiring the use of solvents for their effective extraction and recovery. The conventional use of toxic volatile organic solvents (VOCs) like hexane, petroleum ether, and dimethyl sulfoxide in the extraction of microbial carotenoids has been common. However, ongoing research is introducing innovative, non-toxic, environmentally friendly tailor-made solvents, such as ionic liquids (IL) and deep eutectic solvents (DES), indicating a new era of cleaner and biocompatible technologies. This review aims to highlight recent advancements in utilizing IL and DES for obtaining carotenoids from microorganisms. Additionally, we explore the utilization of in silico tools designed to determine the solubilities of microbial carotenoids in tailor-made DES and ILs. This presents a promising alternative for the scientific community, potentially reducing the need for extensive experimental screening of solvents for the recovery of microbial carotenoids in the separation processing. According to our expert perspective, both IL and DES exhibit a plethora of exceptional attributes for the recovery of microbial carotenoids. Nevertheless, the current employment of these solvents for recovery of carotenoids is restricted to scientific exploration, as their feasibility for practical application in industrial settings has yet to be conclusively demonstrated.

Key points

• ILs and DES share many tailoring properties for the recovery of microbial carotenoids

• The use of ILs and DES for microbial carotenoid extraction remains driven by scientific curiosity.

• The economic feasibility of ILs and DES is yet to be demonstrated in industrial applications.
Characterization of a recombinant Aspergillus niger GZUF36 lipase immobilized by ionic liquid modification strategy
Authors: Xing Shuqi , Long Jia , Xie Wei , Luo Chaocheng , He Laping , Li Cuiqin , Zeng Xuefeng
Published: February 2024

Enzyme immobilized on magnetic nanomaterials is a promising biocatalyst with efficient recovery under applied magnets. In this study, a recombinant extracellular lipase from Aspergillus niger GZUF36 (PEXANL1) expressed in Pichia pastoris GS115 was immobilized on ionic liquid-modified magnetic nano ferric oxide (Fe3O4@SiO2@ILs) via electrostatic and hydrophobic interaction. The morphology, structure, and properties of Fe3O4@SiO2@ILs and immobilized PEXANL1 were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, x-ray diffraction, vibration sample magnetometer, and zeta potential analysis. Under optimized conditions, the immobilization efficiency and activity recovery of immobilized PEXANL1 were 52 ± 2% and 122 ± 2%, respectively. The enzymatic properties of immobilized PEXANL1 were also investigated. The results showed that immobilized PEXANL1 achieved the maximum activity at pH 5.0 and 45 °C, and the lipolytic activity of immobilized PEXANL1 was more than twice that of PEXANL1. Compared to PEXANL1, immobilized PEXANL1 exhibited enhanced tolerance to temperature, metal ions, surfactants, and organic solvents. The operation stability experiments revealed that immobilized PEXANL1 maintained 86 ± 3% of its activity after 6 reaction cycles. The enhanced catalytic performance in enzyme immobilization on Fe3O4@SiO2@ILs made nanobiocatalysts a compelling choice for bio-industrial applications. Furthermore, Fe3O4@SiO2@ILs could also benefit various industrial enzymes and their practical uses.

Key points

• Immobilized PEXANL1 was confirmed by SEM, FT-IR, and XRD.

• The specific activity of immobilized PEXANL1 was more than twice that of PEXANL1.

• Immobilized PEXANL1 had improved properties with good operational stability.

Graphical abstract
Enhancing predictability of IDH mutation status in glioma patients at initial diagnosis: a comparative analysis of radiomics from MRI, [18F]FET PET, and TSPO PET
Authors: Kaiser Lena , Quach S. , Zounek A. J. , Wiestler B. , Zatcepin A. , Holzgreve A. , Bollenbacher A. , Bartos L. M. , Ruf V. C. , Böning G. , Thon N. , Herms J. , Riemenschneider M. J. , Stöcklein S. , Brendel M. , Rupprecht R. , Tonn J. C. , Bartenstein P. , von Baumgarten L. , Ziegler S. , Albert N. L.
Published: February 2024

Purpose

According to the World Health Organization classification for tumors of the central nervous system, mutation status of the isocitrate dehydrogenase (IDH) genes has become a major diagnostic discriminator for gliomas. Therefore, imaging-based prediction of IDH mutation status is of high interest for individual patient management. We compared and evaluated the diagnostic value of radiomics derived from dual positron emission tomography (PET) and magnetic resonance imaging (MRI) data to predict the IDH mutation status non-invasively.

Methods

Eighty-seven glioma patients at initial diagnosis who underwent PET targeting the translocator protein (TSPO) using [18F]GE-180, dynamic amino acid PET using [18F]FET, and T1-/T2-weighted MRI scans were examined. In addition to calculating tumor-to-background ratio (TBR) images for all modalities, parametric images quantifying dynamic [18F]FET PET information were generated. Radiomic features were extracted from TBR and parametric images. The area under the receiver operating characteristic curve (AUC) was employed to assess the performance of logistic regression (LR) classifiers. To report robust estimates, nested cross-validation with five folds and 50 repeats was applied.

Results

TBRGE-180 features extracted from TSPO-positive volumes had the highest predictive power among TBR images (AUC 0.88, with age as co-factor 0.94). Dynamic [18F]FET PET reached a similarly high performance (0.94, with age 0.96). The highest LR coefficients in multimodal analyses included TBRGE-180 features, parameters from kinetic and early static [18F]FET PET images, age, and the features from TBRT2 images such as the kurtosis (0.97).

Conclusion

The findings suggest that incorporating TBRGE-180 features along with kinetic information from dynamic [18F]FET PET, kurtosis from TBRT2, and age can yield very high predictability of IDH mutation status, thus potentially improving early patient management.
Toripalimab, a therapeutic monoclonal anti-PD-1 antibody with high binding affinity to PD-1 and enhanced potency to activate human T cells
Authors: Rajasekaran Narendiran , Wang Xiaoguang , Ravindranathan Sruthi , Chin Daniel J , Tseng Su-Yi , Klakamp Scott L , Widmann Kate , Kapoor Varun N , Vexler Vladimir , Keegan Patricia , Yao Sheng , LaVallee Theresa , Khare Sanjay D
Published: February 2024

Over the past decade, US Food and Drug Administration (FDA)-approved immune checkpoint inhibitors that target programmed death-1 (PD-1) have demonstrated significant clinical benefit particularly in patients with PD-L1 expressing tumors. Toripalimab is a humanized anti-PD-1 antibody, approved by FDA for first-line treatment of nasopharyngeal carcinoma in combination with chemotherapy. In a post hoc analysis of phase 3 studies, toripalimab in combination with chemotherapy improved overall survival irrespective of PD-L1 status in nasopharyngeal carcinoma (JUPITER-02), advanced non-small cell lung cancer (CHOICE-01) and advanced esophageal squamous cell carcinoma (JUPITER-06). On further characterization, we determined that toripalimab is molecularly and functionally differentiated from pembrolizumab, an anti-PD-1 mAb approved previously for treating a wide spectrum of tumors. Toripalimab, which binds the FG loop of PD-1, has 12-fold higher binding affinity to PD-1 than pembrolizumab and promotes significantly more Th1- and myeloid-derived inflammatory cytokine responses in healthy human PBMCs in vitro. In an ex vivo system employing dissociated tumor cells from treatment naïve non-small cell lung cancer patients, toripalimab induced several unique genes in IFN-γ and immune cell pathways, showed different kinetics of activation and significantly enhanced IFN-γ signature. Additionally, binding of toripalimab to PD-1 induced lower levels of SHP1 and SHP2 recruitment, the negative regulators of T cell activation, in Jurkat T cells ectopically expressing PD-1. Taken together, these data demonstrate that toripalimab is a potent anti-PD-1 antibody with high affinity PD-1 binding, strong functional attributes and demonstrated clinical activity that encourage its continued clinical investigation in several types of cancer.
Caffeine gum improves 5 km running performance in recreational runners completing parkrun events
Authors: Lynn Anthony , Shaw Chloe , Sorsby Anna C. , Ashworth Pippa , Hanif Faysal , Williams Claire E. , Ranchordas Mayur K.
Published: February 2024

Purpose

The purpose of this study was to determine whether caffeine gum improves the performance of recreational runners completing parkruns (weekly, 5 km, mass participant running events).

Methods

Thirty-six recreational runners (M = 31, F = 5; age 33.7 ± 10.7 y; BMI 23.1 ± 2.4 kg/m2) capable of running 5 km in < 25 min were recruited to a study at the Sheffield Hallam parkrun, UK. Runners were block randomized into one of three double-blind, placebo-controlled, cross-over intervention trials with caffeine gum as the treatment (n = 6 per intervention trial) or into one of three non-intervention trials that ran concurrently with the intervention trials (n = 6 per non-intervention trial). Changes in conditions across different parkruns were adjusted for using data from the non-intervention trials. Runners in the randomized cross-over intervention trials chewed gum supplying 300 mg of caffeine or a placebo gum for 5 min, starting 30 min before each parkrun.

Results

Caffeine gum improved 5 km parkrun performance by a mean of 17.28 s (95% CI 4.19, 30.37; P = 0.01). Adjustment for environmental conditions using data from the non-intervention trials attenuated the statistical significance (P = 0.04). Caffeine gum also decreased RPE by 1.21 (95% CI 0.30, 2.13; P = 0·01) units relative to placebo.

Conclusions

A 300 mg dose of caffeine supplied in chewing gum improved the performance of recreational runners completing 5 km parkruns by an average of 17 s.

Trial Registration

The study was registered at ClinicalTrials.gov: NCT02473575 before recruitment commenced.
Comparison of five different fluoroscopic methods for identifying the MPFL femoral footprint
Authors: Emre Tuluhan Yunus , Cetin Hakan , Selcuk Huseyin , Kilic Koray Kaya , Aykanat Faruk , Sarikcioglu Levent , Kose Ozkan
Published: February 2024

Purpose

The success of medial patellofemoral ligament (MPFL) reconstruction is closely linked to the precise positioning of the femoral tunnel. Intraoperative fluoroscopy is commonly utilized to identify the MPFL footprint. This study aimed to ascertain the most accurate fluoroscopic method among the five previously described methods used to determine the MPFL femoral footprint.

Materials and methods

Using 44 well-preserved dry femur bones, the MPFL femoral insertion site was demarcated using anatomical bony landmarks, namely the center of the saddle sulcus between the medial epicondyle, adductor tubercle and gastrocnemius tubercle. Fluoroscopic true lateral knee images were acquired and measurements taken, referencing established methods by Schottle et al., Redfern et al., Wijdicks et al., Barnett et al., and Kaipel et al. The distance between anatomic and fluoroscopic MPFL footprints was then measured on digital fluoroscopic images. The accuracy of the locations was compared using a margin of error of 5 and 7 mm.

Results

The Schottle method consistently emerged superior, showcasing the smallest mean distance (3.2 ± 1.2 mm) between the anatomic and radiographic MPFL footprints and a high in-point detection rate of 90.9% under 5 mm criteria. While the Redfern method displayed perfect accuracy (100%) within the 7 mm criteria, the Schottle method also performed 97.7% accuracy.

Conclusions

For intraoperative identification of the MPFL footprint using fluoroscopy, the Schottle method is the most consistent and accurate among the assessed methods. Thus, its accuracy in detecting the MPFL footprint makes it recommended for MPFLR to ensure optimal outcomes.

Level of evidence

Level IV, cadaveric study.
Mutational spectrum in patients with dominant non-syndromic hearing loss in Austria
Authors: Frohne Alexandra , Vrabel Sybille , Laccone Franco , Neesen Juergen , Roesch Sebastian , Dossena Silvia , Schoefer Christian , Frei Klemens , Parzefall Thomas
Published: February 2024

Purpose

Hearing loss (HL) is often monogenic. The clinical importance of genetic testing in HL may further increase when gene therapy products become available. Diagnoses are, however, complicated by a high genetic and allelic heterogeneity, particularly of autosomal dominant (AD) HL. This work aimed to characterize the mutational spectrum of AD HL in Austria.

Methods

In an ongoing prospective study, 27 consecutive index patients clinically diagnosed with non-syndromic AD HL, including 18 previously unpublished cases, were analyzed using whole-exome sequencing (WES) and gene panels. Novel variants were characterized using literature and bioinformatic means. Two additional Austrian medical centers provided AD HL mutational data obtained with in-house pipelines. Other Austrian cases of AD HL were gathered from literature.

Results

The solve rate (variants graded as likely pathogenic (LP) or pathogenic (P)) within our cohort amounted to 59.26% (16/27). MYO6 variants were the most common cause. One third of LP/P variants were truncating variants in haploinsufficiency genes. Ten novel variants in HL genes were identified, including six graded as LP or P. In one cohort case and one external case, the analysis uncovered previously unrecognized syndromic presentations.

Conclusion

More than half of AD HL cases analyzed at our center were solved with WES. Our data demonstrate the importance of genetic testing, especially for the diagnosis of syndromic presentations, enhance the molecular knowledge of genetic HL, and support other laboratories in the interpretation of variants.
Assessment of Schlemm’s canal with swept-source optical coherence tomography in Graves’ ophthalmopathy
Authors: Gün Raziye Dönmez , Yazıcıoğlu Titap , Oklar Murat , Gökkaya Naile
Published: February 2024

Purpose

To evaluate the Schlemm’s canal (SC) parameters obtained by swept-source optical coherence tomography (OCT) different in Graves’ ophthalmopathy (GO) eyes compared to healthy eyes.

Methods

This cross-sectional observational study evaluated 64 eyes of 32 GO cases and 56 eyes of 28 healthy controls. The study was conducted between October 2020 and June 2021. SC images were obtained from the temporal limbus of individuals using swept-source OCT. SC length (SCL) and SC area (SCA) were measured. The relationship between SC parameters in the patient group and intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, Graves’ disease (GD) duration, and clinical activity score (CAS) was evaluated.

Results

In the GO group, 64 eyes of 32 patients were evaluated, and in the age and gender-matched healthy control group, 56 eyes of 28 individuals were assessed. SC images from 4 eyes of 4 patients in the patient group and 1 eye of 1 patient in the control group were not clear, preventing SCL and SCA measurements for these eyes. SCL and SCA measurements were found to be lower, and IOP and Hertel values were higher in the GO group compared to the healthy controls. However, no significant correlation was observed between SCL and SCA with IOP, RNFL thickness, GD duration, GO duration, or CAS in the GO group. In the GO group, the mean value of SCA was found to be higher in eyes with glaucoma or OHT compared to those without.

Conclusion

These findings indicate that SC in GO-affected eyes is shorter and has a smaller area than in healthy individuals. Additionally, higher IOP and Hertel values were observed in the GO group compared to healthy controls. This study suggests that assessing SC using anterior segment OCT could provide valuable insights into the regulation of IOP and the development of glaucoma in GO-affected eyes.
Relationship between wintering site and survival in a migratory waterbird using different migration routes
Authors: Ferreira Hugo R. S. , Champagnon Jocelyn , Alves José A. , Lok Tamar
Published: February 2024

When wintering at different sites, individuals from the same breeding population can experience different conditions, with costs and benefits that may have implications throughout their lifetime. Using a dataset from a longitudinal study on Eurasian Spoonbills from southern France, we explored whether survival rate varied among individuals using different wintering sites. In the last 13 years, more than 3000 spoonbills have been ringed as chicks in Camargue. These birds winter in five main regions that vary in both migratory flyway (East Atlantic vs. Central European) and migration distance (long-distance vs. short-distance vs. resident). We applied Cormack–Jolly–Seber models and found evidence for apparent survival to correlate with migration distance, but not with flyway. During the interval between the first winter sighting and the next breeding period, long-distance migrants had the lowest survival, independently of the flyway taken. Additionally, as they age, spoonbills seem to better cope with migratory challenges and wintering conditions as no differences in apparent survival among wintering strategies were detected during subsequent years. As dispersal to other breeding colonies was rarely observed, the lower apparent survival during this period is likely to be partly driven by lower true survival. This supports the potential role of crossing of natural barriers and degradation of wintering sites in causing higher mortality rates as recorded for a variety of long-distance migrants. Our work confirms variation in demographic parameters across winter distribution ranges and reinforces the importance of longitudinal studies to better understand the complex demographics of migratory species.
A new crack-tip element for the logarithmic stress-singularity of Mode-III cracks in spring interfaces
Authors: Mantič V. , Vázquez-Sánchez A. , Romero-Laborda M. , Muñoz-Reja M. , Jiménez-Alfaro S. , Távara L.
Published: February 2024

A new crack-tip finite element able to improve the accuracy of Finite Element Method (FEM) solutions for cracks growing along the Winkler-type spring interfaces between linear elastic adherents is proposed. The spring model for interface fracture, sometimes called Linear-Elastic (perfectly) Brittle Interface Model (LEBIM), can be used, e.g., to analyse fracture of adhesive joints with a thin adhesive layer. Recently an analytical expression for the asymptotic elastic solution with logarithmic stress-singularity at the interface crack tip considering spring-like interface behaviour under fracture Mode III was deduced by some of the authors. Based on this asymptotic solution, a special 5-node triangular crack-tip finite element is developed. The generated special singular shape functions reproduce the radial behaviour of the first main term and shadow terms of the asymptotic solution. This special element implemented in a FEM code written in Matlab has successfully passed various patch tests with spring boundary conditions. The new element allows to model cracks in spring interfaces without the need of using excessively refined FEM meshes, which is one of the current disadvantages in the use of LEBIM when stiff spring interfaces are considered. Numerical tests carried out by h-refinement of uniform meshes show that the new singular element consistently provides significantly more accurate results than the standard finite elements, especially for stiff interfaces, which could be relevant for practical applications minimizing computational costs. The new element can also be used to solve other problems with logarithmic stress-singularities.
Trends in nutritional status and factors affecting prognostic nutritional index in ovarian cancer patients during chemotherapy: a prospective longitudinal study based on generalized estimating equations
Authors: Mengqin Zhang , Yalin He , Xing Liu , Ya Liu , Yalin Tian , Xin Dan , Jianhua Ren
Published: February 2024

Purpose

Numerous studies have investigated the relationships between nutritional status and the prognosis of ovarian cancer (OC). However, the majority of these studies have focused on pre-chemotherapy malnutrition, with limited attention given to dynamic changes in nutritional status during chemotherapy and the associated risk factors affecting the prognostic nutritional index (PNI) in OC women. This study aims to explore the variation trend in the nutritional status of OC women over time during chemotherapy and assess its predictive factors.

Methods

A prospective longitudinal study was conducted from January 2021 to August 2023. Body mass index (BMI), PNI, Nutritional Risk Screening (NRS) 2002, serum albumin, and prealbumin measurements were utilized to assess the nutritional status of OC women. Data were collected through face-to-face interviews before initial chemotherapy (T0) and during the first (T1), third (T2), and fifth (T3) cycles of chemotherapy. Generalized Estimating Equations (GEE) were employed for the analysis of potential predictive factors.

Results

A total of 525 OC women undergoing chemotherapy completed the study. Significantly varied levels of BMI, PNI, and serum concentrations of hemoglobin, albumin, prealbumin, potassium, sodium, magnesium, and calcium were observed in these patients (p < 0.05). The prevalence of nutritional risk decreased over time during chemotherapy (p < 0.05). Nutritional parameters, including BMI, PNI, and the serum concentrations of albumin and prealbumin, exhibited an upward trend in nutritional status throughout the chemotherapy cycles (p < 0.05). Multivariate analysis indicated that higher levels of BMI, serum albumin, prealbumin, absolute lymphocyte count, and hemoglobin ≥ 110 g/L at admission were associated with elevated PNI after chemotherapy (β = 0.077, p = 0.028; β = 0.315, p < 0.001; β = 0.009, p < 0.001; β = 1.359, p < 0.001; β =  − 0.637, p = 0.005).

Conclusion

Patients consistently demonstrated improvements in nutritional risk and status from the initiation to the completion of chemotherapy cycles. Nutritional monitoring of OC women, particularly those exhibiting abnormalities at the commencement of chemotherapy, is crucial. Targeted nutritional support programs should be developed to enhance the prognosis of OC women.
A proactive financial navigation intervention in patients with newly diagnosed gastric and gastroesophageal junction adenocarcinoma
Authors: Bell-Brown Ari , Hopkins Talor , Watabayashi Kate , Overstreet Karen , Leahy Anthony , Bradshaw Erin , Gallagher Kathleen , Obenchain Jennifer , Padron Amber , Scott Beth , Flores Brooke , Shankaran Veena
Published: February 2024

Purpose

Many cancer patients and caregivers experience financial hardship, leading to poor outcomes. Gastric and gastroesophageal junction (GEJ) cancer patients are particularly at risk for financial hardship given the intensity of treatment. This pilot randomized study among gastric/GEJ cancer patients and caregivers tested a proactive financial navigation (FN) intervention to obtain a signal of efficacy to inform a larger, more rigorous randomized study.

Methods

We tested a 3-month proactive FN intervention among gastric/GEJ cancer patients and caregivers compared to usual care. Caregiver participation was optional. The primary endpoint was incidence of financial hardship, defined as follows: accrual of debt, income decline of ≥ 20%, or taking loans to pay for treatment. Data from participant surveys and documentation by partner organizations delivering the FN intervention was analyzed and outcomes were compared between study arms.

Results

Nineteen patients and 12 caregivers consented. Primary FN resources provided included insurance navigation, budget planning, and help with out-of-pocket medical expenses. Usual care patients were more likely to experience financial hardship (50% vs 40%) and declines in quality of life (37.5% vs 0%) compared to intervention patients. Caregivers in both arms reported increased financial stress and poorer quality of life over the study period.

Conclusions

Proactive financial navigation has potentially positive impacts on financial hardship and quality of life for cancer patients and more large-scale randomized interventions should be conducted to rigorously explore the impact of similar interventions. Interventions that have the potential to lessen caregiver financial stress and burden need further exploration.

Trial registration

TRN: NCT03986502, June 14, 2019.
Association of dietary live microbe intake with diabetic kidney disease in patients with type 2 diabetes mellitus in US adults: a cross-sectional study of NHANES 1999–2018
Authors: Wang Min , Huang Zhao-hui , Zhu Yong-hong , Li Shuai , Li Xin , Sun He , He Ping , Peng Ya-li , Fan Qiu-Ling
Published: February 2024

Aims

Several studies have reported dietary microorganisms’ beneficial effects on human health. We aimed to detect the potential association between dietary live microbe intake and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) through a cross-sectional analysis of the National Health and Nutrition Examination Survey from 1999 to 2018.

Methods

According to the Sanders classification system of dietary live microbes, the study participants were divided into three groups: low, medium, and high live microbe groups. In patients with T2DM, DKD was assessed by glomerular filtration rate (< 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration algorithm), proteinuria (urinary albumin to creatinine ratio ≥ 30 mg/g), or both. Weighted univariate and multivariate logistic regression and subgroup analyses were conducted to investigate the independent association between dietary live microbe and DKD.

Results

The study included 3836 participants, of whom 1467 (38.24%) had DKD for the diagnosis. Our study demonstrated that participants in the high dietary live microbe group were more likely to be older, female, non-Hispanic White, have higher education levels, have a lower prevalence of smoking, have a high poverty-income ratio, have higher energy intake, lower haemoglobin (HbA1c) and serum creatinine levels, and lower risk of progression. After adjustment for covariates, patients in the high dietary live microbe group had a low prevalence of DKD, whereas no significant association with DKD was found between the medium and low dietary live microbe groups. No statistically significant interaction was observed in all subgroup analyses except for HbA1c (p for interaction < 0.05).

Conclusions

Our results indicate that high dietary live microbe intake was associated with a low DKD prevalence.
An objective skill assessment framework for microsurgical anastomosis based on ALI scores
Authors: Gholami Soheil , Manon Anaëlle , Yao Kunpeng , Billard Aude , Meling Torstein R.
Published: February 2024

Introduction

The current assessment and standardization of microsurgical skills are subjective, posing challenges in reliable skill evaluation. We aim to address these limitations by developing a quantitative and objective framework for accurately assessing and enhancing microsurgical anastomosis skills among surgical trainees. We hypothesize that this framework can differentiate the proficiency levels of microsurgeons, aligning with subjective assessments based on the ALI score.

Methods

We select relevant performance metrics from the literature on laparoscopic skill assessment and human motor control studies, focusing on time, instrument kinematics, and tactile information. This information is measured and estimated by a set of sensors, including cameras, a motion capture system, and tactile sensors. The recorded data is analyzed offline using our proposed evaluation framework. Our study involves 12 participants of different ages (

$$35.42\pm 9.78$$

35.42
±
9.78

years) and genders (nine males and three females), including six novice and six intermediate subjects, who perform surgical anastomosis procedures on a chicken leg model.

Results

We show that the proposed set of objective and quantitative metrics to assess skill proficiency aligns with subjective evaluations, particularly the ALI score method, and can effectively differentiate novices from more proficient microsurgeons. Furthermore, we find statistically significant disparities, where microsurgeons with intermediate level of skill proficiency surpassed novices in both task speed, reduced idle time, and smoother, briefer hand displacements.

Conclusion

The framework enables accurate skill assessment and provides objective feedback for improving microsurgical anastomosis skills among surgical trainees. By overcoming the subjectivity and limitations of current assessment methods, our approach contributes to the advancement of surgical education and the development of aspiring microsurgeons. Furthermore, our framework emerges to precisely distinguish and classify proficiency levels (novice and intermediate) exhibited by microsurgeons.
Instrumental assessment of pressure pain threshold over trigeminal and extra-trigeminal area in people with episodic and chronic migraine: a cross-sectional observational study
Authors: Deodato Manuela , Granato Antonio , Martini Miriam , Sabot Raffaele , Buoite Stella Alex , Manganotti Paolo
Published: February 2024

Background

Central and peripheral sensitization are characterized by widespread hyperalgesia that is manifested by larger pain extent area and reduction in pressure pain threshold (PPT). PPT decreases in patients with migraine not only over the trigeminal cervical complex but also throughout the body.

Methods

A cross-sectional study was adopted to assess the local and widespread hyperalgesia in chronic and episodic migraine patients respect to healthy controls. The guidelines of Andersen’s were used to evaluate the PPT bilaterally over 3 muscles in the trigemino-cervical complex (temporalis, sub-occipitalis, trapezius) and over 1 muscle far from this area (tensor fasciae latae).

Results

Thirty subjects with episodic migraine (35.8 ± 2.82 years), 30 with chronic migraine (53.03 ± 19.79 years), and 30 healthy controls (29.06 ± 14.03 years) were enrolled. The interaction effect was present for the trapezius muscle with a significant difference between the right and the left side in episodic group (p = 0.003). A group effect was highlighted in all four muscles analyzed such as suboccipital (p < 0.001), temporalis (p > 0.001), trapezius (p < 0.001), and TFL (p < 0.001). PPT was usually higher in the control group than in the episodic group which in turn was characterized by higher PPT values than the chronic group.

Conclusions

People with chronic and episodic migraine presented lower PPT than healthy controls both in the trigeminal and in the extra-trigeminal area. People with chronic migraine presented lower PPT than episodic migraine only in the trigeminal area. Temporalis and sub-occipitalis are the most sensitive muscles in people with chronic and episodic migraine.
Local mitigation of higher-order ionospheric effects in DFMC SBAS and system performance evaluation
Authors: Sophan Somkit , Supnithi Pornchai , Myint Lin M. M. , Saito Susumu , Hozumi Kornyanat , Nishioka Michi
Published: February 2024

Dual-frequency multi-constellation (DFMC) satellite-based augmentation system (SBAS) is a new SBAS standard for aeronautical navigation systems. It supports aircraft navigation from the enroute to approach phases via the L1 and L5 frequencies (1575.42 and 1176.45 MHz). Although the ionosphere-free (IF) combination in the DFMC SBAS operation removes the first-order ionospheric delays in the pseudorange measurement, remaining terms including the satellite-clock offset errors and higher-order ionospheric (HOI) delays are still unaccounted for. The DFMC SBAS accuracy and integrity can be affected by the HOI effects, especially during severe ionospheric disturbances. In this work, we present the local DFMC SBAS corrections with and without the mitigation of HOI delays. We first estimate the HOI delay terms using the received pseudorange followed by separate satellite and receiver bias estimations based on the minimum sum-variance technique. The integrity terms can then be obtained. The performances of DFMC SBAS using the global navigation satellite system (GNSS) data including GPS, Galileo, and QZSS are evaluated using obtained GNSS data at stations in Thailand on the ionospheric quiet and disturbed days. The results show that with the HOI mitigation, the vertical positioning errors (VPE) on the quiet and disturbed days can be improved by 12% and 9%, whereas the vertical protection levels (VPL) are improved by 16% and 21%, respectively. In addition, we perform a preliminary assessment of DFMC SBAS based on the International Civil Aviation Organization (ICAO) requirements of two categories: Localizer Performance with Vertical guidance (LPV-200) and Category I precision approach (CAT-I) showing promising results.
Deep Learning for Perfusion Cerebral Blood Flow (CBF) and Volume (CBV) Predictions and Diagnostics
Authors: Talebi Salmonn , Gai Siyu , Sossin Aaron , Zhu Vivian , Tong Elizabeth , Mofrad Mohammad R. K.
Published: February 2024

Dynamic susceptibility contrast magnetic resonance perfusion (DSC-MRP) is a non-invasive imaging technique for hemodynamic measurements. Various perfusion parameters, such as cerebral blood volume (CBV) and cerebral blood flow (CBF), can be derived from DSC-MRP, hence this non-invasive imaging protocol is widely used clinically for the diagnosis and assessment of intracranial pathologies. Currently, most institutions use commercially available software to compute the perfusion parametric maps. However, these conventional methods often have limitations, such as being time-consuming and sensitive to user input, which can lead to inconsistent results; this highlights the need for a more robust and efficient approach like deep learning. Using the relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) perfusion maps generated by FDA-approved software, we trained a multistage deep learning model. The model, featuring a combination of a 1D convolutional neural network (CNN) and a 2D U-Net encoder-decoder network, processes each 4D MRP dataset by integrating temporal and spatial features of the brain for voxel-wise perfusion parameters prediction. An auxiliary model, with similar architecture, but trained with truncated datasets that had fewer time-points, was designed to explore the contribution of temporal features. Both qualitatively and quantitatively evaluated, deep learning-generated rCBV and rCBF maps showcased effective integration of temporal and spatial data, producing comprehensive predictions for the entire brain volume. Our deep learning model provides a robust and efficient approach for calculating perfusion parameters, demonstrating comparable performance to FDA-approved commercial software, and potentially mitigating the challenges inherent to traditional techniques.
Transforming self-experienced vulnerability into professional strength: a dialogical narrative analysis of medical students’ reflective writing
Authors: Valestrand Eivind Alexander , Kvernenes Monika , Kinsella Elizabeth Anne , Hunskaar Steinar , Schei Edvin
Published: February 2024

Medical students’ efforts to learn person-centered thinking and behavior can fall short due to the dissonance between person-centered clinical ideals and the prevailing epistemological stereotypes of medicine, where physicians’ life events, relations, and emotions seem irrelevant to their professional competence. This paper explores how reflecting on personal life experiences and considering the relevance for one’s future professional practice can inform first-year medical students’ initial explorations of professional identities. In this narrative inquiry, we undertook a dialogical narrative analysis of 68 essays in which first-year medical students reflected on how personal experiences from before medical school may influence them as future doctors. Students wrote the texts at the end of a 6-month course involving 20 patient encounters, introduction to person-centered theory, peer group discussions, and reflective writing. The analysis targeted medical students’ processes of interweaving and delineating personal and professional identities. The analysis yielded four categories. (1) How medical students told their stories of illness, suffering, and relational struggles in an interplay with context that provided them with new perspectives on their own experiences. Students formed identities with a person-centered orientation to medical work by: (2) recognizing and identifying with patients’ vulnerability, (3) experiencing the healing function of sharing stories, and (4) transforming personal experiences into professional strength. Innovative approaches to medical education that encourage and support medical students to revisit, reflect on, and reinterpret their emotionally charged life experiences have the potential to shape professional identities in ways that support person-centered orientations to medical work.
Flood risk assessment and adaptation under changing climate for the agricultural system in the Ghanaian White Volta Basin
Authors: Smits Wouter K. , Attoh Emmanuel M. N. A. N. , Ludwig Fulco
Published: February 2024

In the context of river basins, the threat of climate change has been extensively studied. However, many of these studies centred on hazard analysis while neglecting the need for comprehensive risk assessments that account for exposure and vulnerability. Hazard analysis alone is not adequate for making adaptive decisions. Thus, to effectively manage flood risk, it is essential to understand the elements that contribute to vulnerability and exposure in addition to hazard analysis. This study aims to assess flood risk (in space and time until the year 2100) for the agricultural system, in the White Volta Basin in northern Ghana. Employing the impact chain methodology, a mix of quantitative and qualitative data and techniques were used to assess hazard, exposure, and vulnerability. Multi-model climate change data (RCP 8.5) from CORDEX and observation data from the Ghana Meteorological Agency were used for hazard analysis. Data on exposure, vulnerability, and adaptation were collected through structured interviews. Results indicate that flood hazard will increase by 79.1% with high spatial variability of wet periods but the flood risk of the catchment will increase by 19.3% by the end of the twenty-first century. The highest flood risk is found in the Upper East region, followed by North East, Northern, Savannah, and Upper West for all four analysed periods. Adaptive capacity, sensitivity, and exposure factors are driven by poverty, ineffective institutional governance, and a lack of livelihood alternatives. We conclude that the region is highly susceptible and vulnerable to floods, and that shifting from isolated hazard analysis to a comprehensive assessment that considers exposure and vulnerability reveals the underlying root causes of the risk. Also, the impact chain is useful in generating insight into flood risk for policymakers and researchers. We recommend the need to enhance local capacity and foster social transformation in the region.
Experiences of Clients and Professionals with the Recovery Oriented Intake
Authors: Engelsbel Fabiana , Waterhout Nanette , Dijkstra Marty , Keet René , Nugter Annet
Published: February 2024

The Recovery Oriented Intake (ROI) integrates recovery principles from the start of treatment, and involves peer experts, unlike the intake as usual (IAU). This study compared experiences with ROI and IAU among 127 clients and 391 professionals, consisting of practitioners and peer experts. Intake’s quality, measured with questionnaires, showed no differences in experiences between ROI and IAU clients. However, practitioners experienced ROI as more recovery-oriented than IAU. The ROI Fidelity Check (RFC) revealed that clients’ RFC-scores, but not practitioners’, predicted their valuation of intake’s quality. This underscores the need for (re)training and peer supervision for professionals to ensure adherence to ROI’s principles. Discrepancies between clients’ and professionals’ experiences at the start of treatment are consistent with literature on working alliance and Shared Decision Making (SDM). Differences between ROI and IAU professionals may stem from heightened awareness of recovery principles due to training and the presence of peer experts during intake.
Antihypertensive drug targets and breast cancer risk: a two-sample Mendelian randomization study
Authors: Zheng Guoqiao , Chattopadhyay Subhayan , Sundquist Jan , Sundquist Kristina , Ji Jianguang
Published: February 2024

Findings on the correlation between the use of antihypertensive medication and the risk of breast cancer (BC) have been inconsistent. We performed a two-sample Mendelian randomization (MR) using instrumental variables to proxy changes in gene expressions of antihypertensive medication targets to interrogate this. Genetic instruments for expression of antihypertensive drug target genes were identified with expression quantitative trait loci in blood, which should be associated with systolic blood pressure to proxy for the effect of antihypertensive drug. The association between genetic variants and BC risk were obtained from genome-wide association study summary statistics. The summary-based MR was employed to estimate the drug effects on BC risk. We further performed sensitivity analyses to confirm the discovered MR associations such as assessment of horizontal pleiotropy, colocalization, and multiple tissue enrichment analyses. The overall BC risk was only associated with SLC12A2 gene expression at a Bonferroni-corrected threshold. One standard deviation (SD) decrease of SLC12A2 gene expression in blood was associated with a decrease of 1.12 (95%CI, 0.80–1.58) mmHg of systolic blood pressure, but a 16% increased BC risk (odds ratio, 1.16, 95% confidential interval, 1.06–1.28). This signal was further observed for estrogen receptor positive (ER +) BC (1.17, 1.06–1.28). In addition, one SD decrease in expression of PDE1B in blood was associated with 7% decreased risk of ER + BC (0.93, 0.90–0.97). We detected no evidence of horizontal pleiotropy for these associations and the probability of the causal variants being shared between the gene expression and BC risk was 81.5, 40.5 and 66.8%, respectively. No significant association was observed between other target gene expressions and BC risk. Changes in expression of SLC12A2 and PDE1B mediated possibly via antihypertensive drugs may result in increased and decreased BC risk, respectively.