bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of a multi-epitope vaccine against goatpox virus using an immunoinformatics approach
Authors: Long Qinqin , Wei Min , Wang Yuting , Pang Feng
Published: February 2024

Introduction

Goatpox, a severe infectious disease caused by goatpox virus (GTPV), leads to enormous economic losses in the livestock industry. Traditional live attenuated vaccines cause serious side effects and exist a risk of dispersal. Therefore, it is urgent to develop efficient and safer vaccines to prevent and control of GTPV.

Methods

In the present study, we are aimed to design a multi-epitope subunit vaccine against GTPV using an immunoinformatics approach. Various immunodominant cytotoxic T lymphocytes (CTL) epitopes, helper T lymphocytes (HTL) epitopes, and B-cell epitopes from P32, L1R, and 095 proteins of GTPV were screened and liked by the AAY, GPGPG, and KK connectors, respectively. Furthermore, an adjuvant β-defensin was attached to the vaccine’s N-terminal using the EAAAK linker to enhance immunogenicity.

Results

The constructed vaccine was soluble, non-allergenic and non-toxic and exhibited high levels of antigenicity and immunogenicity. The vaccine’s 3D structure was subsequently predicted, refined and validated, resulting in an optimized model with a Z-value of -3.4. Molecular docking results demonstrated that the vaccine had strong binding affinity with TLR2(-27.25 kcal/mol), TLR3(-39.84 kcal/mol), and TLR4(-59.42 kcal/mol). Molecular dynamics simulation results indicated that docked vaccine-TLR complexes were stable. Immune simulation analysis suggested that the vaccine can induce remarkable increase in antibody titers of IgG and IgM, higher levels of IFN-γ and IL-2.

Conclusion

The designed GTPV multi-epitope vaccine is structurally stable and can induce robust humoral and cellular immune responses, which may be a promising vaccine candidate against GTPV.
Efficacy of federated learning on genomic data: a study on the UK Biobank and the 1000 Genomes Project
Authors: Kolobkov Dmitry , Mishra Sharma Satyarth , Medvedev Aleksandr , Lebedev Mikhail , Kosaretskiy Egor , Vakhitov Ruslan
Published: February 2024

Combining training data from multiple sources increases sample size and reduces confounding, leading to more accurate and less biased machine learning models. In healthcare, however, direct pooling of data is often not allowed by data custodians who are accountable for minimizing the exposure of sensitive information. Federated learning offers a promising solution to this problem by training a model in a decentralized manner thus reducing the risks of data leakage. Although there is increasing utilization of federated learning on clinical data, its efficacy on individual-level genomic data has not been studied. This study lays the groundwork for the adoption of federated learning for genomic data by investigating its applicability in two scenarios: phenotype prediction on the UK Biobank data and ancestry prediction on the 1000 Genomes Project data. We show that federated models trained on data split into independent nodes achieve performance close to centralized models, even in the presence of significant inter-node heterogeneity. Additionally, we investigate how federated model accuracy is affected by communication frequency and suggest approaches to reduce computational complexity or communication costs.
Carbon isotope values of hazelnut shells: a new proxy for canopy density
Authors: Styring Amy K. , Jirdén Elin , Lagerås Per , Larsson Mikael , Sjöström Arne , Ljung Karl
Published: February 2024

Hazel (Corylus avellana) has been abundant in the vegetation of northern and central Europe since the early Holocene and has provided food and materials for humans ever since. Here we use stable carbon isotope (δ13C) values of hazelnut shells to infer woodland openness based on the premise of the “canopy effect”. It is well established that plants growing in dense, shaded forests have lower carbon isotope (δ13C) values than plants growing in open areas. By measuring δ13C values in hazelnuts collected from trees growing in different levels of light intensity, we show that the canopy effect is preserved in hazelnuts and that their δ13C values can be used to infer woodland openness in the past. We apply the method to hazelnuts recovered from sites dated to between the Mesolithic and Iron Age (c. 7000 BCE−1000 CE) in southern Sweden. Our results show that the nuts dated to the Mesolithic were harvested from hazels growing in a range of closed to open settings while nuts from subsequent periods were harvested from progressively more open environments. Given the abundance of hazelnuts recovered from many archaeological contexts, this method has the potential to reconstruct the microhabitats exploited by humans in the past and explore the impact of humans on their environment.
The humane education of Waldorf
Authors: Attfield Kate
Published: February 2024

In this perspective paper I propose to explore the remarkable humanity-centered education designed by the Austrian philosopher Rudolf Steiner (1861–1925), along with his legacy in the form of the Waldorf schools that still serve children aged 3–18. Steiner was a polymath who could have been influenced by figures including the Roman playwright Terence, a freed slave who valued “humanity,” as well as the 16th Century Humanist Erasmus of Rotterdam, who was in favor of humane education. International Waldorf education is now over 100 years old and Steiner’s focus on educating the human being in a healthy and integrated manner remains central. This paper provides an exploratory overview of Steiner-Waldorf education and offers a critical reflection on issues sometimes raised against its theory and practice. I have interviewed 43 Waldorf teachers from schools in Germany, the US and the UK covering their individual evaluation of human and humane-focused Waldorf pedagogy. The paper concludes that, given external government support, it can remain a visionary movement and a stimulus to other educational systems.
Identification and characterization of a novel CASR mutation causing familial hypocalciuric hypercalcemia
Authors: Lin Chien-Ming , Ding Yi-Xuan , Huang Shih-Ming , Chen Ying-Chuan , Lee Hwei-Jen , Sung Chih-Chien , Lin Shih-Hua
Published: February 2024

Context

Although a monoallelic mutation in the calcium-sensing receptor (CASR) gene causes familial hypocalciuric hypercalcemia (FHH), the functional characterization of the identified CASR mutation linked to the clinical response to calcimimetics therapy is still limited.

Objective

A 45-year-old male presenting with moderate hypercalcemia, hypocalciuria, and inappropriately high parathyroid hormone (PTH) had a good response to cinacalcet (total serum calcium (Ca2+) from 12.5 to 10.1 mg/dl). We identified the genetic mutation and characterized the functional and pathophysiological mechanisms, and then linked the mutation to calcimimetics treatment in vitro.

Design

Sanger sequencing of the CASR, GNA11, and AP2S1 genes was performed in his family. The simulation model was used to predict the function of the identified mutant. In vitro studies, including immunoblotting, immunofluorescence, a cycloheximide chase study, Calbryte™ 520 Ca2+ detection, and half-maximal effective concentration (EC50), were examined.

Results

This proband was found to carry a de novo heterozygous missense I554N in the cysteine-rich domain of CASR, which was pathogenic based on the different software prediction models and ACGME criteria. The simulation model showed that CASR I554N mutation decreased its binding energy with Ca2+. Human CASR I554N mutation attenuated the stability of CASR protein, reduced the expression of p-ERK 1/2, and blunted the intracellular Ca2+ response to gradient extracellular Ca2+ (eCa2+) concentration. The EC50 study also demonstrated the correctable effect of calcimimetics on the function of the CASR I554N mutation.

Conclusion

This novel CASR I554N mutation causing FHH attenuates CASR stability, its binding affinity with Ca2+, and the response to eCa2+ corrected by therapeutic calcimimetics.
Analysis of white matter tract integrity using diffusion kurtosis imaging reveals the correlation of white matter microstructural abnormalities with cognitive impairment in type 2 diabetes mellitus
Authors: Gao Jie , Pan Peichun , Li Jing , Tang Min , Yan Xuejiao , Zhang Xin , Wang Man , Ai Kai , Lei Xiaoyan , Zhang Xiaoling , Zhang Dongsheng
Published: February 2024

Background

This study aimed to identify disruptions in white matter integrity in type 2 diabetes mellitus (T2DM) patients by utilizing the white matter tract integrity (WMTI) model, which describes compartment-specific diffusivities in the intra- and extra-axonal spaces, and to investigate the relationship between WMTI metrics and clinical and cognitive measurements.

Methods

A total of 73 patients with T2DM and 57 healthy controls (HCs) matched for age, sex, and education level were enrolled and underwent diffusional kurtosis imaging and cognitive assessments. Tract-based spatial statistics (TBSS) and atlas-based region of interest (ROI) analysis were performed to compare group differences in diffusional metrics, including fractional anisotropy (FA), mean diffusivity (MD), axonal water fraction (AWF), intra-axonal diffusivity (Daxon), axial extra-axonal space diffusivity (De,//), and radial extra-axonal space diffusivity (De,⊥) in multiple white matter (WM) regions. Relationships between diffusional metrics and clinical and cognitive functions were characterized.

Results

In the TBSS analysis, the T2DM group exhibited decreased FA and AWF and increased MD, De,∥, and De,⊥ in widespread WM regions in comparison with the HC group, which involved 56.28%, 32.07%, 73.77%, 50.47%, and 75.96% of the mean WM skeleton, respectively (P < 0.05, TFCE-corrected). De,⊥ detected most of the WM changes, which were mainly located in the corpus callosum, internal capsule, external capsule, corona radiata, posterior thalamic radiations, sagittal stratum, cingulum (cingulate gyrus), fornix (stria terminalis), superior longitudinal fasciculus, and uniform fasciculus. Additionally, De,⊥ in the genu of the corpus callosum was significantly correlated with worse performance in TMT-A (β = 0.433, P < 0.001) and a longer disease duration (β = 0.438, P < 0.001).

Conclusions

WMTI is more sensitive than diffusion tensor imaging in detecting T2DM-related WM microstructure abnormalities and can provide novel insights into the possible pathological changes underlying WM degeneration in T2DM. De,⊥ could be a potential imaging marker in monitoring disease progression in the brain and early intervention treatment for the cognitive impairment in T2DM.
The occurrence of asthma in an extensive-stage small-cell lung cancer patient after combination therapy with atezolizumab and anlotinib: a case report
Authors: Deng Wang , Chen Juan , Deng Xin-Yu
Published: February 2024

Background

Extensive-stage small-cell lung cancer (ES-SCLC) is highly malignant, with early metastasis and high recurrence. Since therapeutic options are limited, ES-SCLC has a characteristically short survival period and extremely poor prognosis. A combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic drugs can achieve promising efficacy and safety in patients with ES-SCLC as a second-line or subsequent treatment, extending survival to some extent. However, the clinical outcomes remain mostly unsatisfactory and are sometimes affected by treatment-related adverse events.

Case presentation

A 57-year-old woman with ES-SCLC was administered a combination therapy of atezolizumab (a PD-L1 inhibitor) and anlotinib [an oral multi-targeted tyrosine kinase inhibitor (TKI)]. She survived for 22 months, with no disease progression during the 28 courses of therapy. Unexpectedly, despite having no history of asthma, the patient developed asthma while receiving this regimen. This is possibly related to T-cell activation and the tumor immune microenvironment, which induce allergic inflammation after PD-L1 blockade.

Conclusions

This is the first report of an asthma-negative ES-SCLC patient who developed asthma after receiving atezolizumab plus anlotinib. Although this combination therapy may effectively extend survival in SCLC patients, asthmatic symptoms should be closely monitored.
Immunoproteomics enable broad identification of new Aspergillus fumigatus antigens in severe equine asthma
Authors: Jentsch Maria-Christin , Lübke Sabrina , Schrödl Wieland , Volke Daniela , Krizsan Andor , Hoffmann Ralf , Kaiser-Thom Sarah , Gerber Vinzenz , Marti Eliane , Wagner Bettina , Schnabel Christiane L.
Published: February 2024

Introduction

Severe equine asthma (SEA) is a common chronic disease of adult horses with characteristic recurrent airway obstruction and similarities to neutrophilic asthma in humans. As an extrinsic stimulus, hay dust exposure is a major risk factor and induces acute exacerbation in susceptible horses. However, single inducing agents of SEA have hardly been identified on a molecular basis. Aspergillus fumigatus (A. fumigatus) is a common mold species in hay and has been described as a major provoking agent of SEA.

Methods

Aiming to identify disease-relevant antigens, we analyzed A. fumigatus using an immunoproteomics approach on two-dimensional immunoblots of A. fumigatus protein probed with serum from environmentally matched asthmatic and healthy horses (n=5 pairs). A. fumigatus binding serum immunoglobulins (Pan-Ig), and the isotypes IgG4/7 and IgG3/5 were quantified for each protein spot and then compared between asthmatic and healthy horses.

Results and discussion

For 21 out of 289 spots serum immunoglobulin (Ig) binding was different between the two groups for Pan-Ig or the isotypes. If differences were detected, Pan-Ig and IgG4/7 binding to the proteins were lower, while IgG3/5 binding was higher in asthmatic than healthy horse sera. Proteins were extracted from the 21 spots of interest and analyzed by liquid chromatography mass spectrometry. Eight prioritized proteins (candidate antigens) were expressed as recombinant proteins. Some of these have been previously described as major or minor A. fumigatus allergens, alongside other proteins, most with hydrolase activity. Recombinant candidate antigens were tested on 1D immunoblots to confirm their relevance as antigens by serum antibody binding. Four proteins (beta-hexosaminidase, class II aldolase/adducin domain protein, glucoamylase, peptide hydrolase B0XX53) showed different antibody binding characteristics between asthmatic and healthy horses and are likely relevant antigens in SEA. Their identification can provide the basis for innovative diagnostics, prevention, or therapeutic approaches. Additionally, a more profound understanding of SEA and its potential underlying mechanisms can be established. Elevated serum IgG3/5 antibodies correlate with T helper cell 2 responses in other equine pathologies, and the recombinant SEA antigens developed here can become instrumental in analyzing the involvement of SEA-specific T cell responses and Ig responses in future studies.
Peritumoral brain zone in glioblastoma: biological, clinical and mechanical features
Authors: Ballestín Alberto , Armocida Daniele , Ribecco Valentino , Seano Giorgio
Published: February 2024

Glioblastoma is a highly aggressive and invasive tumor that affects the central nervous system (CNS). With a five-year survival rate of only 6.9% and a median survival time of eight months, it has the lowest survival rate among CNS tumors. Its treatment consists of surgical resection, subsequent fractionated radiotherapy and concomitant and adjuvant chemotherapy with temozolomide. Despite the implementation of clinical interventions, recurrence is a common occurrence, with over 80% of cases arising at the edge of the resection cavity a few months after treatment. The high recurrence rate and location of glioblastoma indicate the need for a better understanding of the peritumor brain zone (PBZ). In this review, we first describe the main radiological, cellular, molecular and biomechanical tissue features of PBZ; and subsequently, we discuss its current clinical management, potential local therapeutic approaches and future prospects.
Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy
Authors: Bar Jair , Leibowitz Raya , Reinmuth Niels , Ammendola Astrid , Jacob Eyal , Moskovitz Mor , Levy-Barda Adva , Lotem Michal , Katsenelson Rivka , Agbarya Abed , Abu-Amna Mahmoud , Gottfried Maya , Harkovsky Tatiana , Wolf Ido , Tepper Ella , Loewenthal Gil , Yellin Ben , Brody Yehuda , Dahan Nili , Yanko Maya , Lahav Coren , Harel Michal , Raveh Shoval Shani , Elon Yehonatan , Sela Itamar , Dicker Adam P. , Shaked Yuval
Published: February 2024

Introduction

Immune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.

Methods

Pre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using clinical benefit and overall survival as endpoints. Bioinformatic analyses of upregulated proteins were performed to determine potential cell origins and enriched biological processes.

Results

The levels of 142 proteins were significantly increased in the plasma of NSCLC patients following ICI-based treatments. Soluble PD-1 exhibited the highest increase, with a positive correlation to tumor PD-L1 status, and, in the ICI monotherapy dataset, an association with improved overall survival. Bioinformatic analysis of the ICI monotherapy dataset revealed a set of 30 upregulated proteins that formed a single, highly interconnected network, including CD8A connected to ten other proteins, suggestive of T cell activation during ICI treatment. Notably, the T cell-related network was detected regardless of clinical benefit. Lastly, circulating proteins of alveolar origin were identified as potential biomarkers of limited clinical benefit, possibly due to a link with cellular stress and lung damage.

Conclusions

Our study provides insights into the biological processes activated during ICI-based therapy, highlighting the potential of plasma proteomics to identify mechanisms of therapy resistance and biomarkers for outcome.
Biological testing of ships’ ballast water indicates challenges for the implementation of the Ballast Water Management Convention
Authors: Outinen Okko , Bailey Sarah A. , Casas-Monroy Oscar , Delacroix Stephanie , Gorgula Sonia , Griniene Evelina , Kakkonen Jenni E. , Srebaliene Greta
Published: February 2024

Ships’ ballast water and sediments are vectors that contribute to the unintentional spread of aquatic non-native species globally. Ballast water management, as well as commissioning testing of ballast water management systems and compliance monitoring under the regulations of the International Maritime Organization (IMO) aim at minimizing the unwanted spread of organisms. This study compiles data for treated ballast water samples collected and analyzed from 228 ships during 2017–2023. The samples were collected from the ballast discharge line or directly from the ballast tank for enumeration of living organism concentrations in the categories of ≥50µm and <50 to ≥10µm -sized organisms, as well as indicator microbes in comparison to the ballast water performance standard of the IMO (Regulation D-2). In addition, several ship-specific factors were examined to infer potential factors affecting compliance rates. Nearly all ships were compliant with the ballast water performance standard for indicator microbes and <50 to ≥10µm -sized organisms, whereas almost half of all samples exceeded the limit of ten viable organisms m-3 for the ≥50µm -sized organisms. Compliance testing results did not differ significantly between sampling years, indicating that compliance rate did not change through time. The rate of compliance was higher for commissioning testing than compliance testing. Clear ship- or system-specific factors that lead to compliance or non-compliance were not detected, even though type of ballast water management system, filter mesh size associated with the system and source of ballast water affected compliance significantly either for the samples taken from the discharge line, or ballast tank. As compliance did not improve significantly over time, compliance testing of ships’ ballast water should be undertaken to ensure that the systems remain operational after commissioning and ships meet requirements of the D-2 standard. Furthermore, the study outcomes promote further research on the efficiency of filter mesh sizes and different filtration units associated with ballast water management systems, to improve mechanical removal of larger organisms. Finally, as several ships exceeded the compliance limit by hundreds or thousands of living organisms, technological advancements and operational measures may be needed to improve the overall reliability of ballast water management.
Spatial–temporal distribution characteristics of Harpadon nehereus in the Yangtze River Estuary and its relationship with environmental factors
Authors: Li Yu , Gao Chunxia , Chen Jinhui , Wang Qing , Zhao Jing
Published: February 2024

To investigate the spatial–temporal distribution characteristics of Harpadon nehereus in the Yangtze River Estuary (YRE) and its relationship with environmental factors, this study used the data from resource and environmental surveys conducted in the YRE and adjacent waters during August (summer) and November (autumn), 2017–2022. Generalized additive models (GAM) were employed to analyze the relationships between the relative resources of H. nehereus and environmental factors and to predict the spatial–temporal distribution of H. nehereus resources in 2022. Our results revealed that the best model deviance explained in summer and autumn was 64.89% and 49.90%, with average effect sizes of 0.75 and 0.70, respectively, for cross-validated regression slopes. Water temperature and salinity were identified as the key environmental factors influencing the relative resources of H. nehereus in the YRE. Overall, there were notable seasonal differences in the relationship between the relative resources of H. nehereus and environmental factors. The relative resources of H. nehereus in the YRE were higher in the summer than in autumn. In summer, both water temperature and salinity exhibited multi-wave nonlinear relationships with the relative resources of H. nehereus, while in autumn, the relative resources of H. nehereus showed a positive linear relationship with water temperature and a non-linear relationship with salinity. Additionally, the predicted and observed values of the relative resources of H. nehereus in 2022 showed similar spatial distribution patterns. The relative resources of H. nehereus was higher in the northern branch than in the southern branch and the offshore regions compared to the near-estuary regions. Altogether, our study provides a scientific basis for conservation management and sustainable utilization of H. nehereus resources in the YRE, thereby contributing to the restoration and management of fishery resources in the region.
Distribution and influencing factors of macrobenthos on three seagrass beds in the intertidal zone of Shandong province, China
Authors: Ji Yinglu , Song Bo , Xu Jiangling , Jiang Shaoyu , Chen Linlin , Li Baoquan
Published: February 2024

Introduction

The macrobenthos plays a vital role within the ecosystem of seagrass beds, with its characteristics and spatial distribution serving as indicators of the well-being of the seagrass beds.

Methods

In August 2018, three seagrass beds located in the Yellow River Estuary of Dongying, the west coast of Yantai, and Swan Lake of Weihai, were investigated to compare the ecological influences of seagrass habitat on the benthic environment and macrobenthic community. Within each seagrass bed, porewater, sediment, and macrobenthos were sampled from three separate stations (center of seagrass bed, edge of seagrass bed and bare area).

Results and discussion

One-way ANOVA showed significant differences (p < 0.05) in environmental factors and macrobenthos species, abundance, biomass and diversity indices among the three seagrass beds. The present data did not show significant impacts on habitat and macrobenthos in the different coverage areas of seagrass beds at the investigated spatial scales, though crustacea and some carnivores were relatively more inclined to inhabit areas with higher seagrass densities. Aquaculture and eutrophication may trigger the loss of seagrass bed habitats, that affects macrobenthic biodiversity, and conservation measures are needed to protect seagrass bed habitats.
Relation between beluga whale aggregations and sea temperature on climate change forecasts
Authors: Rivas Marga L. , Guirado Emilio , Ortega Zaida
Published: February 2024

Climate change has been shown to alter the spatial distribution of whales and other marine mammals. Fast changing ocean temperatures may also affect the spatial distribution of whales at a finer scale, namely within populations, including aggregation behaviour. Our ability to analyze the impact of climate change on whale aggregation behavior, however, has been limited by our ability to collect spatial observation data over large areas. To overcome this limitation, this study analyzed open-access satellite imagery obtained between 2007 and 2020 in Canada, Russia, and Alaska using Deep Convolutional Neural Networks (CNN) to detect 1,980 beluga whales in 11 populations and to quantify their aggregation patterns within their populations. Subsequently, we examined the relationship between sea surface temperature (SST) and the intra-population spatial patterns of beluga whales during summer seasons, when these whales normally aggregate. We detected a negative correlation between SST and the frequency of beluga whale aggregation, suggesting that warming temperatures may impact beluga whale spatio-behavioral dynamics. Considering that the relative abundance of beluga whales is declining and the future SST projections in these Arctic Ocean locations, climate change may pose yet another threat to beluga whales and other ice-dependent species.
Potential role of physical labor and cultural views of menstruation in high incidence of pelvic organ prolapse in Nepalese women: a comparative study across the menstrual cycle
Authors: Biswokarma Yvonne , Brandon Karen , Lohman Everett , Stafford Ryan , Daher Noha , Petrofsky Jerold , Thapa Uma , Berk Lee , Hitchcock Robert , Hodges Paul W.
Published: February 2024

Introduction

Pelvic organ prolapse (POP) is a significant health concern for young Nepali women, with potential risk factors including pelvic floor trauma from vaginal delivery and heavy lifting. The prevalence of symptomatic POP (SPOP) among nulliparous women in Nepal is 6%, while the general population of Nepali women aged 15–49 years reports a prevalence of 7%. Surprisingly, the average age of SPOP onset in Nepal is 27 years, challenging the assumption that postmenopausal age and vaginal delivery are the sole risk factors. This study aims to investigate the influence of increased intra-abdominal pressure (IAP) during lifting tasks on pelvic organ descent in Nepali women across different menstrual cycle stages.

Methods

The study included 22 asymptomatic Nepali women aged 18–30 years who regularly engage in heavy lifting. Intra-abdominal pressure was measured intra-vaginally during typical and simulated lifting tasks, which encompassed various scenarios such as ballistic lifting, ramped lifting, and pre-contraction of pelvic floor muscles, as well as coughing, Valsalva maneuver, and pelvic floor contractions. Pelvic floor displacement was recorded using transperineal ultrasound during menstruation, ovulation, and the mid-luteal phase.

Results

Results indicated that pelvic floor displacement was greater during menstruation than ovulation when performing a simulated ballistic lifting task (6.0 ± 1.6 mm vs. 5.1 ± 1.5 mm, p = 0.03, d = 0.6). However, there was no significant difference in pelvic floor displacement during lifting when the pelvic muscles were pre-contracted.

Conclusion

These findings suggest that lifting heavy loads during menstruation may increase the risk of stretching and injuring pelvic floor supportive tissues, potentially contributing to SPOP in young Nepali women. Pre-contracting pelvic floor muscles during lifting tasks may offer a protective effect. Understanding these factors could aid in developing targeted preventive measures and raising awareness about the impact of heavy lifting on pelvic floor health among Nepali women.
Efficacy of vestibular rehabilitation and its facilitating and hindering factors from real-world clinical data
Authors: Kim Min-Ku , Yun So-Yeon , Lee Seonkyung , Lee Ja-Ok , Sung Soo-Yun , Lee Ju-Young , Kim Hyo-Jung , Park Hye Youn , Choi Jeong-Yoon , Song Jae-Jin , Choi Byung Yoon , Koo Ja-Won , Kim Ji-Soo
Published: February 2024

Background and purpose

Customized vestibular rehabilitation improved dizziness and imbalance in several randomized controlled trials. In the present study, we determined the efficacy of customized vestibular rehabilitation using real-world observational data.

Methods

In this retrospective observational study, we recruited 64 patients (median age = 60, interquartile range = 48–66.3) who completed the customized vestibular rehabilitation from January to December 2022. The outcomes of rehabilitation were evaluated using the dizziness handicap inventory (DHI) or vestibular disorders activities of daily living scale (VADL). The factors associated with outcomes were assessed with a generalized linear model, of which covariates included patients’ age, sex, duration of illness, type of vestibular disorders, initial DHI and VADL scores, exercise compliance, and initial hospital anxiety and depression scale (HADS) scores.

Results

After the median of 6 (4–6) weeks of rehabilitation, DHI and VADL scores significantly improved in patients with either peripheral or central vestibular disorders (Wilcoxon signed-rank test, p < 0.05). The initial DHI and VADL scores showed a positive while the sum of HADS scores showed a negative correlation with the outcome. In contrast, the age, sex, duration of illness, types of vestibular disorders, and exercise compliance did not affect the outcome.

Discussion and conclusion

Customized vestibular rehabilitation is effective for central as well as peripheral disorders, especially when the symptoms are severe and the psychological distress is mild.
Establishing an MSU service in a medium-sized German urban area—clinical and economic considerations
Authors: Rink Johann S. , Tollens Fabian , Tschalzev Andrej , Bartelt Christian , Heinzl Armin , Hoffmann Jens , Schoenberg Stefan O. , Marzina Annika , Sandikci Vesile , Wiegand Carla , Hoyer Carolin , Szabo Kristina
Published: February 2024

Background and purpose

Mobile stroke units (MSU) have been demonstrated to improve prehospital stroke care in metropolitan and rural regions. Due to geographical, social and structural idiosyncrasies of the German city of Mannheim, concepts of established MSU services are not directly applicable to the Mannheim initiative. The aim of the present analysis was to identify major determinants that need to be considered when initially setting up a local MSU service.

Methods

Local stroke statistics from 2015 to 2021 were analyzed and circadian distribution of strokes and local incidence rates were calculated. MSU patient numbers and total program costs were estimated for varying operating modes, daytime coverage models, staffing configurations which included several resource sharing models with the hospital. Additional case-number simulations for expanded catchment areas were performed.

Results

Median time of symptom onset of ischemic stroke patients was 1:00 p.m. 54.3% of all stroke patients were admitted during a 10-h time window on weekdays. Assuming that MSU is able to reach 53% of stroke patients, the average expected number of ischemic stroke patients admitted to MSU would be 0.64 in a 10-h shift each day, which could potentially be increased by expanding the MSU catchment area. Total estimated MSU costs amounted to € 815,087 per annum. Teleneurological assessment reduced overall costs by 11.7%.

Conclusion

This analysis provides a framework of determinants and considerations to be addressed during the design process of a novel MSU program in order to balance stroke care improvements with the sustainable use of scarce resources.
Successful switch to ofatumumab after liver injury associated with ocrelizumab treatment in multiple sclerosis: a case report
Authors: Mariottini Alice , Barilaro Alessandro , Lotti Antonio , Marra Fabio , Massacesi Luca
Published: February 2024

Drug-induced liver injury (DILI) is a potential adverse event of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS), as well as of methylprednisolone pulsed therapy used in case of MS relapse. DILI may be induced by different mechanisms, including idiosyncratic reaction, autoimmune hepatitis or viral reactivation. In patients receiving the humanized anti-CD20 monoclonal antibody (mAb) ocrelizumab, DILI has been rarely reported and was mostly associated with hepatitis B virus (HBV) reactivation. Here we present the case of a woman with highly active relapsing–remitting MS who had experienced two episodes of DILI while receiving different DMTs, and was successfully switched to ofatumumab, a fully human anti-CD20 mAb, after a further event associated with ocrelizumab treatment and unrelated to HBV reactivation. Despite sharing the mechanism of action, differences in structure, pharmacokinetic/pharmacodynamic profile, and use of ancillary drugs (only needed for ocrelizumab) may have accounted for the successful switch. To our knowledge, this is the first report of a successful switch from ocrelizumab to ofatumumab due to DILI. Ofatumumab may therefore represent a valid therapeutic option for patients experiencing DMTs- and ocrelizumab-induced liver injury, providing that HBV reactivation has been ruled out.
Slowing gait during turning: how volition of modifying walking speed affects the gait pattern in healthy adults
Authors: Madrid Julian , Benning Leo , Selig Mischa , Ulrich Baptiste , Jolles Brigitte M. , Favre Julien , Benninger David H.
Published: February 2024

Background

Turning during walking and volitionally modulating walking speed introduces complexity to gait and has been minimally explored.

Research question

How do the spatiotemporal parameters vary between young adults walking at a normal speed and a slower speed while making 90°, 180°, and 360° turns?

Methods

In a laboratory setting, the spatiotemporal parameters of 10 young adults were documented as they made turns at 90°, 180°, and 360°. A generalized linear model was utilized to determine the effect of both walking speed and turning amplitude.

Results

Young adults volitionally reducing their walking speed while turning at different turning amplitudes significantly decreased their cadence and spatial parameters while increasing their temporal parameters. In conditions of slower movement, the variability of certain spatial parameters decreased, while the variability of some temporal parameters increased.

Significance

This research broadens the understanding of turning biomechanics in relation to volitionally reducing walking speed. Cadence might be a pace gait constant synchronizing the rhythmic integration of several inputs to coordinate an ordered gait pattern output. Volition might up-regulate or down-regulate this pace gait constant (i.e., cadence) which creates the feeling of modulating walking speed.
Caregiver self-efficacy providing nutritional support for pediatric patients undergoing hematopoietic stem cell transplant is associated with psychosocial factors
Authors: LaLonde Leah , Neenan Alexandra , Byrd Michelle , Hoodin Flora , Bouma Sandra , Choi Sung Won
Published: February 2024

Introduction

Caregiver self-efficacy in providing nutritional support to pediatric hematopoietic stem cell transplantation (HSCT) patients has been little studied despite the increased risk of these children potentially being over- or under-nourished after HSCT, and nutritional status could possibly affect treatment outcomes. The current study aimed to describe caregiver dietary self-efficacy and its associated psychosocial factors and barriers to following dietary recommendations.

Methods

Caregivers completed questionnaires pre-HSCT and 30 days, 100 days, and one year post-HSCT. A subset provided a 24-h recall of food intake.

Results

Results showed generally high caregiver confidence and low difficulty supporting their child nutritionally. However, lower confidence was associated with higher caregiver depression, anxiety, and stress 30 days post-HSCT. Further, higher difficulty at various time points was correlated with lower income, higher depression and anxiety, stress, and miscarried helping (i.e., negative caregiver-child interactions surrounding eating), as well as child overweight status and failure to meet protein intake guidelines. Nutritional criteria for protein, fiber, added sugar, and saturated fat were met by 65%, 0%, 75%, and 75%, respectively. Caregiver attitudes and child behavior were the most frequently reported barriers to healthy eating.

Discussion

Results suggest that directing resources to caregivers struggling emotionally, economically, or transactionally could support pediatric patients undergoing HSCT in maintaining optimal nutritional status.
Expert consensus on nutrition and lower-carbohydrate diets: An evidence- and equity-based approach to dietary guidance
Authors: Volek Jeff S. , Yancy William S. , Gower Barbara A. , Phinney Stephen D. , Slavin Joanne , Koutnik Andrew P. , Hurn Michelle , Spinner Jovonni , Cucuzzella Mark , Hecht Frederick M.
Published: February 2024

There is a substantial body of clinical evidence supporting the beneficial effects of lower-carbohydrate dietary patterns on multiple established risk factors associated with insulin resistance and cardiovascular diseases in adult populations. Nutrition and health researchers, clinical practitioners, and stakeholders gathered for, “The Scientific Forum on Nutrition, Wellness, and Lower-Carbohydrate Diets: An Evidence- and Equity-Based Approach to Dietary Guidance” to discuss the evidence base around lower-carbohydrate diets, health outcomes, and dietary guidance. Consensus statements were agreed upon to identify current areas of scientific agreement and spotlight gaps in research, education, and practice to help define and prioritize future pathways. Given the evidence base and considering that most American adults are living with at least one nutrition-related chronic disease, there was consensus that including a lower-carbohydrate dietary pattern as one part of the Dietary Guidelines for Americans could help promote health equity among the general population.
Amide proton transfer imaging has added value for predicting extraprostatic extension in prostate cancer patients
Authors: Qin Xiaoyan , Lv Jian , Zhang Jianmei , Mu Ronghua , Zheng Wei , Liu Fuzhen , Huang Bingqin , Li Xin , Yang Peng , Deng Kan , Zhu Xiqi
Published: February 2024

Background

Prostate cancer invades the capsule is a key factor in selecting appropriate treatment methods. Accurate preoperative prediction of extraprostatic extension (EPE) can help achieve precise selection of treatment plans.

Purpose

The aim of this study is to verify the diagnostic efficacy of tumor size, length of capsular contact (LCC), apparent diffusion coefficient (ADC), and Amide proton transfer (APT) value in predicting EPE. Additionally, the study aims to investigate the potential additional value of APT for predicting EPE.

Method

This study include 47 tumor organ confined patients (age, 64.16 ± 9.18) and 50 EPE patients (age, 61.51 ± 8.82). The difference of tumor size, LCC, ADC and APT value between groups were compared. Binary logistic regression was used to screen the EPE predictors. The receiver operator characteristic curve analysis was performed to assess the diagnostic performance of variables for predicting EPE. The diagnostic efficacy of combined models (model I: ADC+LCC+tumor size; model II: APT+LCC+tumor size; and model III: APT +ADC+LCC+tumor size) were also analyzed.

Results

APT, ADC, tumor size and the LCC were independent predictors of EPE. The area under the curve (AUC) of APT, ADC, tumor size and the LCC were 0.752, 0.665, 0.700 and 0.756, respectively. The AUC of model I, model II, and model III were 0.803, 0.845 and 0.869, respectively. The cutoff value of APT, ADC, tumor size and the LCC were 3.65%, 0.97×10−3mm2/s, 17.30mm and 10.78mm, respectively. The sensitivity/specificity of APT, ADC, tumor size and the LCC were 76%/89.4.0%, 80%/59.6%, 54%/78.9%, 72%/66%, respectively. The sensitivity/specificity of model I, Model II and Model III were 74%/72.3%, 82%/72.5% and 84%/80.9%, respectively.

Data conclusion

Amide proton transfer imaging has added value for predicting EPE. The combination model of APT balanced the sensitivity and specificity.
Optimizing aspirin dose for colorectal cancer patients through deep phenotyping using novel biomarkers of drug action
Authors: Patrignani Paola , Tacconelli Stefania , Contursi Annalisa , Piazuelo Elena , Bruno Annalisa , Nobili Stefania , Mazzei Matteo , Milillo Cristina , Hofling Ulrika , Hijos-Mallada Gonzalo , Sostres Carlos , Lanas Angel
Published: February 2024

Background: Low-dose aspirin’s mechanism of action for preventing colorectal cancer (CRC) is still debated, and the optimal dose remains uncertain. We aimed to optimize the aspirin dose for cancer prevention in CRC patients through deep phenotyping using innovative biomarkers for aspirin’s action.

Methods: We conducted a Phase II, open-label clinical trial in 34 CRC patients of both sexes randomized to receive enteric-coated aspirin 100 mg/d, 100 mg/BID, or 300 mg/d for 3 ± 1 weeks. Biomarkers were evaluated in blood, urine, and colorectal biopsies at baseline and after dosing with aspirin. Novel biomarkers of aspirin action were assessed in platelets and colorectal tissues using liquid chromatography-mass spectrometry to quantify the extent of cyclooxygenase (COX)-1 and COX-2 acetylation at Serine 529 and Serine 516, respectively.

Results: All aspirin doses caused comparable % acetylation of platelet COX-1 at Serine 529 associated with similar profound inhibition of platelet-dependent thromboxane (TX)A2 generation ex vivo (serum TXB2) and in vivo (urinary TXM). TXB2 was significantly reduced in CRC tissue by aspirin 300 mg/d and 100 mg/BID, associated with comparable % acetylation of COX-1. Differently, 100 mg/day showed a lower % acetylation of COX-1 in CRC tissue and no significant reduction of TXB2. Prostaglandin (PG)E2 biosynthesis in colorectal tumors and in vivo (urinary PGEM) remained unaffected by any dose of aspirin associated with the variable and low extent of COX-2 acetylation at Serine 516 in tumor tissue. Increased expression of tumor-promoting genes like VIM (vimentin) and TWIST1 (Twist Family BHLH Transcription Factor 1) vs. baseline was detected with 100 mg/d of aspirin but not with the other two higher doses.

Conclusion: In CRC patients, aspirin 300 mg/d or 100 mg/BID had comparable antiplatelet effects to aspirin 100 mg/d, indicating similar inhibition of the platelet’s contribution to cancer. However, aspirin 300 mg/d and 100 mg/BID can have additional anticancer effects by inhibiting cancerous tissue’s TXA2 biosynthesis associated with a restraining impact on tumor-promoting gene expression. EUDRACT number: 2018-002101-65.

Clinical Trial Registration:ClinicalTrials.gov, identifier NCT03957902.
Translational frontiers: insight from lymphatics in skin regeneration
Authors: Jiang Yujia , Perez-Moreno Mirna
Published: February 2024

The remarkable regenerative ability of the skin, governed by complex molecular mechanisms, offers profound insights into the skin repair processes and the pathogenesis of various dermatological conditions. This understanding, derived from studies in human skin and various model systems, has not only deepened our knowledge of skin regeneration but also facilitated the development of skin substitutes in clinical practice. Recent research highlights the crucial role of lymphatic vessels in skin regeneration. Traditionally associated with fluid dynamics and immune modulation, these vessels are now recognized for interacting with skin stem cells and coordinating regeneration. This Mini Review provides an overview of recent advancements in basic and translational research related to skin regeneration, focusing on the dynamic interplay between lymphatic vessels and skin biology. Key highlights include the critical role of stem cell-lymphatic vessel crosstalk in orchestrating skin regeneration, emerging translational approaches, and their implications for skin diseases. Additionally, the review identifies research gaps and proposes potential future directions, underscoring the significance of this rapidly evolving research arena.
The prognostic value of preoperative D-dimer to albumin ratio for overall survival and progression-free survival in colorectal cancer
Authors: Wei Lishuang , Xie Hailun , Wang Qiwen , Tang Shuangyi , Gan Jialiang
Published: February 2024

Introduction: This study aimed to explore the predictive value of the D-dimer-to-albumin ratio (DAR) for progression-free survival (PFS) and overall survival (OS) in patients with colorectal cancer (CRC).

Methods: The Kaplan-Meier method was used to plot survival curves for PFS and OS. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive efficacy of the DAR for PFS and OS in patients with CRC. Cox proportional hazards regression analysis was used to analyze prognostic factors influencing outcomes. A nomogram based on the DAR was constructed to predict 1-, 3-, and 5-year prognoses of patients with CRC; its predictive ability was evaluated using the concordance index (C-index) and calibration curves. Additionally, the clinical utility of the DAR-based nomogram was validated using an internal randomized validation cohort.

Results: A total of 1,339 patients with CRC who underwent surgery were enrolled. The optimal cut-off value for DAR was determined to be 3.320, dividing patients into low (<3.320 [n = 470]) and high (≥3.320 [n = 869]) DAR groups. Compared with other composite immune inflammatory markers, DAR exhibited superior prognostic predictive efficacy. Patients with a high DAR had a significantly worse prognosis than those with a low DAR (PFS, 50.9% versus [vs.] 69.4%, p < 0.001; OS, 52.9% vs. 73.8%, p < 0.001). DAR also demonstrated significant prognostic stratification for most tumor subgroups, particularly in the stage III-IV subgroup and normal carcinoembryonic antigen subgroup. DAR has been identified as an independent predictive indicator of PFS/OS in patients with CRC. For every standard deviation increase in DAR, the risk for PFS/OS in patients with CRC was reduced by 9.5% (hazard ratio [HR] 1.095 [95% confidence interval (CI) 1.013–1.185]; p = 0.022) and 9.3% (HR 1.093 [95% CI 1.012–1.180]; p = 0.024), respectively. The DAR-based nomogram was confirmed to demonstrate good prognostic prediction accuracy and achieved high evaluation in the internal validation cohort.

Conclusion: Preoperative DAR is a promising biomarker for predicting PFS and OS among patients with CRC. The DAR-based prognostic prediction nomogram may serve as an effective tool for the comprehensive assessment of prognosis in patients with CRC.