bluuebunny/crossref_metadata_2025 huggingface dataset:
GGT5: a potential immunotherapy response inhibitor in gastric cancer by modulating GSH metabolism and sustaining memory CD8+ T cell infiltration
Authors: Zhao Wenjing , Liang Ziwei , Yao Yongshi , Ge Yang , An Guangyu , Duan Ling , Yao Jiannan
Published: May 2024

Purpose

The variable responses to immunotherapy observed in gastric cancer (GC) patients can be attributed to the intricate nature of the tumor microenvironment. Glutathione (GSH) metabolism significantly influences the initiation and progression of gastric cancer. Consequently, targeting GSH metabolism holds promise for improving the effectiveness of Immune checkpoints inhibitors (ICIs).

Methods

We investigated 16 genes related to GSH metabolism, sourced from the MSigDB database, using pan-cancer datasets from TCGA. The most representative prognosis-related gene was identified for further analysis. ScRNA-sequencing analysis was used to explore the tumor heterogeneity of GC, and the results were confirmed by  Multiplex immunohistochemistry (mIHC).

Results

Through DEGs, LASSO, univariate and multivariate Cox regression analyses, and survival analysis, we identified GGT5 as the hub gene in GSH metabolism with the potential to promote GC. Combining CIBERSORT, ssGSEA, and scRNA analysis, we constructed the immune architecture of GC. The subpopulations of T cells were isolated, revealing a strong association between GGT5 and memory CD8+ T cells. Furthermore, specimens from 10 GC patients receiving immunotherapy were collected. mIHC was used to assess the expression levels of GGT5 and memory CD8+ T cell markers. Our results established a positive correlation between GGT5 expression, the enrichment of memory CD8+ T cells, and a suboptimal response to immunotherapy.

Conclusions

Our study identifies GGT5, a hub gene in GSH metabolism, as a potential therapeutic target for inhibiting the response to immunotherapy in GC patients. These findings offer new insights into strategies for optimizing immunotherapy of GC.
Signal enhancement ratio of multi-phase contrast-enhanced MRI: an imaging biomarker for survival in pancreatic adenocarcinoma
Authors: Xia Cong , Qu Jin-rong , Jiao Yi-ping , Lu Chun-qiang , Zhao Ben , Ge Rong-jun , Qiu Yue , Cao Bu-yue , Yu Qian , Xia Tian-yi , Meng Xiang-pan , Song Yang , Zhang Li-hua , Long Xue-ying , Ye Jing , Ding Zhi-min , Cai Wu , Ju Sheng-hong
Published: May 2024

Objectives

To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard.

Methods

This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015–2021). SER is defined as (SIlt − SIpre)/(SIea − SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan–Meier curves.

Results

The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29–0.74, all p < 0.001) and epithelium (r = −0.23 to −0.71, all p < 0.001) across a wide post-injection time window (range, 25–300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17–2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25–2.41), p = 0.001).

Conclusion

SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC.

Clinical relevance statement

The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC.

Key Points

Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma.

Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers.

Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.

Graphical Abstract
Clinicopathologic features and genomic profiling of female axillary lymph node metastases from adenocarcinoma or poorly differentiated carcinoma of unknown primary
Authors: Tang Liansha , Zhu Yueting , Du Yang , Long Xiangyu , Long Yixiu , Tang Yuan , Liu Jiyan
Published: May 2024

Purpose

Axillary lymph node metastases from adenocarcinoma or poorly differentiated carcinoma of unknown primary (CUPAx) is a rare disease in women. This retrospective study intended to examine the clinicopathological features of CUPAx and compared CUPAx genetically with axillary lymph node metastases from breast cancer (BCAx), investigating differences in their biological behavior.

Methods

We conducted the clinical and prognostic analysis of 58 CUPAx patients in West China Hospital spanning from 2009 to 2021. Gemonic profiling of 12 CUPAx patients and 16 BCAx patients was conducted by the FoundationOne CDx (F1CDx) platform. Moreover, we also compared the gene mutation spectrum and relevant pathways between the two groups and both TCGA and COSMIC databases.

Results

The majority of the 58 CUPAx patients were HR-/HER2- subtype. Most patients received mastectomy combined radiotherapy (50 Gy/25f). CUPAx patients who received mastectomy instead of breast-conserving surgery had a more favorable overall prognosis. Radiotherapy in chest wall/breast and supraclavicular/infraclavicular fossa was the independent prognostic factor (HR = 0.05, 95%CI = 0.00–0.93, P = 0.04). In 28 sequencing samples (CUPAx, n = 12, BCAx, n = 16) and 401 TCGA-BRCA patients, IRS2 only mutated in CUPAx (33.33%) but amplified in BCAx (11.11%) and TCGA-BRCA (1.5%). Pathway analysis revealed that BCAx had more NOTCH pathway mutations than CUPAx. Enrichment analysis showed that CUPAx enriched more in mammary development and PML bodies than BCAx, but less in the positive regulation of kinase activity.

Conclusions

More active treatment methods, like chemotherapy, mastectomy and postoperative radiotherapy, could improve the prognosis of CUPAx. The differential mutation genes of CUPAx and BCAx might be associated with their respective biological behaviors like invasiveness and prognosis.
A study of the effect of half-day climatotherapy on changes in salivary cortisol levels
Authors: Kanayama Hitomi , Kusaka Yukinori , Inoue Hiroyuki , Hirai Takayoshi , Schuh Angela
Published: May 2024

In our previous study setting, climatotherapy programme consisted of six sessions – four in the mid-mountain area and two in a flat park. For all sessions, the subjects underwent climatotherapy in the morning under slightly cool conditions. During each session, the subjects’ blood pressure, pulse rate, skin temperature, blood lactate, salivary cortisol and mood profile were recorded, and meteorological data were collected at the sites. We hypothesised that exercise habits, changes in mood profile and effective temperatures during the session, and physical exertion during the climatic terrain cure would affect salivary cortisol levels. Subjects were 30 (spring) and 29 (autumn). Multiple linear regression analyses were performed to examine the determinants of the change in salivary cortisol levels. In the mountain setting, salivary cortisol was elevated, even though the sessions took place in the descending phase of the circadian salivary cortisol variation; however, the post-session cortisol increase was not significant. Increased post-session salivary cortisol was significantly associated with female gender, older age, higher BMI, lower body fat, less daily physical activity, increased blood lactate, increased ‘Tension-Anxiety’ and ‘Depression-Dejection’ moods, and decreased ‘Anger-Hostility’ mood. The increase in cortisol may have been due to older age, a predominance of females, and the increased blood lactate due to the mountainous terrain. In the flat park, the significant decrease in postsession salivary cortisol was related to the descending circadian phase of circadian cortisol variation and the low physical demands of the sessions.
Damage and Fragmentation of Rock Under Multi-Long-Hole Blasting with Large Empty Holes
Authors: Lan Riyan , Cheng Ruishan , Zhou Zilong , Chen Lu , Wang Peiyu , Wang Zhen
Published: May 2024

The technique of multi-long-hole blasting with large empty holes has been used in practice to break rock mass. However, the damage mechanism of rock mass surrounded by empty holes and boreholes under this type of blasting has not yet been well-understood and identified, which may lead to inappropriate design of the configurations of empty holes for multi-long-hole blasting. The present study investigates the damage modes and mechanism of rock mass under multi-long-hole blasting with large empty holes by conducting a field test and numerical simulations. The results show that multi-long-hole blasting with empty holes mainly causes compressive damage of rock mass around boreholes, reflected tensile damage near empty holes and ground surface, bending-induced tensile damage between empty holes and boreholes, shear damage along the side tangents and bottom of empty holes and boreholes, and tensile damage along the connection of boreholes caused by the superposition of stress waves. In addition, parametric studies are conducted to examine the effects of depths and diameters of empty holes and the spacing between boreholes and empty holes on the damage and fragmentation of rock mass under blast loads. It is found that the flexural stiffness and confined levels of rock mass can be greatly influenced by the variation of configurations of empty holes, which thus induces different damage and fragmentation under multi-long-hole blasting. Analytical formulas for the evaluation of shear and bending-induced damage of rock mass under multi-long-hole blasting are finally proposed to provide references for the design of empty holes in multi-long-hole blasting.
Utility of diffusion tensor imaging and generalized q-sampling imaging for predicting short-term clinical effect of deep brain stimulation in Parkinson’s disease
Authors: Yuzkan Sabahattin , Hasimoglu Ozan , Balsak Serdar , Mutlu Samet , Karagulle Mehmet , Kose Fadime , Altinkaya Ayca , Tugcu Bekir , Kocak Burak
Published: May 2024

Purpose

To assess whether diffusion tensor imaging (DTI) and generalized q-sampling imaging (GQI) metrics could preoperatively predict the clinical outcome of deep brain stimulation (DBS) in patients with Parkinson’s disease (PD).

Methods

In this single-center retrospective study, from September 2021 to March 2023, preoperative DTI and GQI examinations of 44 patients who underwent DBS surgery, were analyzed. To evaluate motor functions, the Unified Parkinson’s Disease Rating Scale (UPDRS) during on- and off-medication and Parkinson’s Disease Questionnaire-39 (PDQ-39) scales were used before and three months after DBS surgery. The study population was divided into two groups according to the improvement rate of scales: ≥ 50% and < 50%. Five target regions, reported to be affected in PD, were investigated. The parameters having statistically significant difference were subjected to a receiver operating characteristic (ROC) analysis.

Results

Quantitative anisotropy (qa) values from globus pallidus externus, globus pallidus internus (qa_Gpi), and substantia nigra exhibited significant distributional difference between groups in terms of the improvement rate of UPDRS-3 scale during on-medication (p = 0.003, p = 0.0003, and p = 0.0008, respectively). In ROC analysis, the best parameter in predicting DBS response included qa_Gpi with a cut-off value of 0.01370 achieved an area under the ROC curve, accuracy, sensitivity, and specificity of 0.810, 73%, 62.5%, and 85%, respectively. Optimal cut-off values of ≥ 0.01864 and ≤ 0.01162 yielded a sensitivity and specificity of 100%, respectively.

Conclusion

The imaging parameters acquired from GQI, particularly qa_Gpi, may have the ability to non-invasively predict the clinical outcome of DBS surgery.
Digital manufacturing techniques and the in vitro biocompatibility of acrylic-based occlusal device materials
Authors: Haugli Ketil Hegerstrøm , Alkarra Dimitri , Samuelsen Jan T.
Published: May 2024

Objectives

Material chemistry and workflow variables associated with the fabrication of dental devices may affect the biocompatibility of the dental devices. The purpose of this study was to compare digital and conventional workflow procedures in the manufacturing of acrylic-based occlusal devices by assessing the cytotoxic potential of leakage products.

Methods

Specimens were manufactured by 3D printing (stereolithography and digital light processing), milling, and autopolymerization. Print specimens were also subjected to different post-curing methods. To assess biocompatibility, a human tongue epithelial cell line was exposed to material-based extracts. Cell viability was measured by MTT assay while Western blot assessed the expression level of selected cytoprotective proteins.

Results

Extracts from the Splint 2.0 material printed with DLP technology and post-cured with the Asiga Flash showed the clearest loss of cell viability. The milled and autopolymerized materials also showed a significant reduction in cell viability. However, by storing the autopolymerized material in dH2O for 12 h, no significant viability loss was observed. Increased levels of cytoprotective proteins were seen in cells exposed to extracts from the print materials and the autopolymerized material. Similarly to the effect on viability loss, storing the autopolymerized material in dH2O for 12 h reduced this effect.

Conclusions/Clinical relevance

Based on the biocompatibility assessments, clinical outcomes of acrylic-based occlusal device materials may be affected by the choice of manufacturing technique and workflow procedures.
Influence of an allogenic collagen scaffold on implant sites with thin supracrestal tissue height: a randomized clinical trial
Authors: Solderer A , Hicklin SP , Aßenmacher M , Ender A , Schmidlin PR
Published: May 2024

Objectives

This randomized clinical trial focused on patients with thin peri-implant soft-tissue height (STH) (≤ 2.5 mm) and investigated the impact of an allogenic collagen scaffold (aCS) on supracrestal tissue height and marginal bone loss (MBL).

Material & methods

Forty patients received bone level implants and were randomly assigned to the test group with simultaneous tissue thickening with aCS or the control group. After three months, prosthetic restoration occurred. STH measurements were taken at baseline (T0) and reopening surgery (TR), with MBL assessed at 12 months (T1). Descriptive statistics were calculated for continuous variables, and counts for categorical variables (significance level, p = 0.05).

Results

At T1, 37 patients were available. At T0, control and test groups had mean STH values of 2.3 ± 0.3 mm and 2.1 ± 0.4 mm. TR revealed mean STH values of 2.3 ± 0.2 mm (control) and 2.6 ± 0.7 mm (test), with a significant tissue thickening of 0.5 ± 0.6 mm in the test group (p < 0.03). At T1, control and test groups showed MBL mean values of 1.1 ± 0.8 mm and 1.0 ± 0.6 mm, with a moderate but significant correlation with STH thickening (-0.34), implant position (0.43), history of periodontitis (0.39), and smoking status (0.27).

Conclusion

The use of an aCS protocol resulted in soft tissue thickening but did not reach a threshold to reliably reduce MBL compared to the control group within the study’s limitations.

Clinical relevance

Peri-implant STH is crucial for maintaining peri-implant marginal bone stability. Marginal bone stability represents a crucial factor in prevention of peri-implantitis development.

German register of clinical trial registration number DRKS00033290.
In “Tone” with dogs: exploring canine musicality
Authors: Pinelli Claudia , Scandurra Anna , Giacoma Cristina , Di Lucrezia Alfredo , D’Aniello Biagio
Published: May 2024

This study investigates the musical perception skills of dogs through playback experiments. Dogs were trained to distinguish between two different target locations based on a sequence of four ascending or descending notes. A total of 16 dogs of different breeds, age, and sex, but all of them with at least basic training, were recruited for the study. Dogs received training from their respective owners in a suitable environment within their familiar home settings. The training sequence consisted of notes [Do-Mi-Sol#-Do (C7-E7-G7#-C8; Hz frequency: 2093, 2639, 3322, 4186)] digitally generated as pure sinusoidal tones. The training protocol comprised 3 sequential training levels, with each level consisting of 4 sessions with a minimum of 10 trials per session. In the test phase, the sequence was transposed to evaluate whether dogs used relative pitch when identifying the sequences. A correct response by the dog was recorded as 1, while an incorrect response, occurring when the dog chose the opposite zone of the bowl, was marked as 0. Statistical analyses were performed using a binomial test. Among 16 dogs, only two consistently performed above the chance level, demonstrating the ability to recognize relative pitch, even with transposed sequences. This study suggests that dogs may have the ability to attend to relative pitch, a critical aspect of human musicality.
Looking backwards to move forwards: insights for climate change adaptation from historical Māori relocation due to natural hazards in Aotearoa New Zealand
Authors: Bailey-Winiata Akuhata P. , Gallop Shari L. , White Iain , Wotherspoon Liam , Fa’aui Tūmanako , Dickson Mark , Ellis Joanne
Published: May 2024

Climate change relocation of Indigenous communities is increasing globally. For Māori (the Indigenous peoples of Aotearoa New Zealand), many pā (complexes of significant structures) are at risk to climate change impacts with relocation as one potential adaptation option. For Indigenous peoples, this step is not taken lightly, as connection to place is imperative. The aim of this research is to highlight some histories of Māori communities relocating in response to natural hazards, providing insights from the past to help plan for future adaptation. To do this, we undertook a national-scale textual analysis and identified 51 examples of pā relocating in response to natural hazards since pre-1840. We then focused on a case study with members of two iwi (tribes), who relocated following the 1886 eruption of Mount Tarawera to identify enablers and barriers to relocation, and to draw insights to assist with Māori-led responses to climate change adaptation. We found that key enablers of relocation included whānau (family)-level decision-making, cultural norms of awhi (support), whanaungatanga (relationships), whakapapa (genealogical connection), koha (donation), tuku whenua (gifts of land), and mātauranga Māori (Māori knowledge). In summary, Māori and other Indigenous peoples have rich histories of relocations, utilising their own Indigenous knowledge, local implementation, and adaptability to natural hazards that can be implemented in our modern context.
Intercontinental invasion dynamics of Cercopagis pengoi, an IUCN-listed planktonic invasive species
Authors: Macêdo Rafael L. , Klippel Gabriel , Silva Daniel P. , Haubrock Phillip J. , Vilela Bruno , Mammola Stefano , Rocha Odete , Franco Ana Clara S.
Published: May 2024

Predicting the spread of invasive species and understanding the role of niche dynamics in niche transferability are critical challenges in the management of biological invasions, both theoretically and practically. We used complementary species distribution modelling approaches, such as multivariate niche analysis and reciprocal distribution models, to test the niche conservatism hypothesis and to predict the potential distribution of the fishhook waterflea, Cercopagis pengoi. Our analysis indicated a significant similarity between its native and invasive ranges, suggesting that a subset of the Ponto-Caspian propagules may have been the founders of European populations. However, our results contradict the niche conservatism hypothesis, showing that C. pengoi has not fully occupied the available niche within its current invasive ranges. Moreover, we observed a notable niche expansion, reflecting a significant shift in niche following its intercontinental introduction in North America. Given the suitability of new environments for the expansion of C. pengoi and its tendency to evade detection prior to population surges, we recommend a focus on early detection through monitoring of both water columns and bottom sediments. This should be complemented by strict enforcement of ballast water regulations to curtail its spread in North America, Europe, and other suitable non-native regions globally.
Markov switching stereotype logit models for longitudinal ordinal data affected by unobserved heterogeneity in responding behavior
Authors: Colombi Roberto , Giordano Sabrina
Published: May 2024

When asked to assess their opinion about attitudes or perceptions on Likert-scale, respondents often endorse the midpoint or extremes of the scale and agree or disagree regardless of the content. These responding behaviors are known in the psychometric literature as middle, extremes, aquiescence and disacquiescence response styles that generally introduce bias in the results. One of the key motivations behind our approach is to account for these attitudes and how they evolve over time. The novelty of our proposal, in the context of longitudinal ordered categorical data, is in considering simultaneously the temporal dynamics of the responses (observable ordinal variables) and unobservable answering behaviors, possibly influenced by response styles, through a Markov switching logit model with two latent components. One component accommodates serial dependence and respondent’s unobserved heterogeneity, the other component determines the responding attitude (due to response styles or not). The dependence of the responses on covariates is modelled by a stereotype logit model with parameters varying according to the two latent components. The stereotype logit model is adopted because it is a flexible extension of the proportional odds logit model that retains the advantage of using a single parameter to describe a regressor effect. In the paper, a new interpretation of the parameters of the stereotype model is given by defining the allocation sets as intervals of values of the linear predictor that identify the most probable response. Unobserved heterogeneity, serial dependence and tendency to response style are modelled through our approach on longitudinal data, collected by the Bank of Italy.
CD3, CD8, IFN-γ, tumor and stroma inflammatory cells as prognostic indicators for surgically resected SCLC: evidences from a 10-year retrospective study and immunohistochemical analysis
Authors: Fu Meng , Feng Chunmei , Wang Jialiang , Guo Chang , Wang Yongguang , Gao Rong , Wang Jiexiao , Zhu Qizhi , Zhang Xiaopeng , Qi Jian , Zhang Yani , Bian Yuting , Wang Zhipeng , Fang Yuan , Cao Lejie , Hong Bo , Wang Hongzhi
Published: May 2024

Current clinical guidelines limit surgical intervention to patients with cT1-2N0M0 small cell lung cancer (SCLC). Our objective was to reassess the role of surgery in SCLC management, and explore novel prognostic indicators for surgically resected SCLC. We reviewed all patients diagnosed with SCLC from January 2011 to April 2021 in our institution. Survival analysis was conducted using the Kaplan–Meier method, and independent prognostic factors were assessed through the Cox proportional hazard model. In addition, immunohistochemistry (IHC) staining was performed to evaluate the predictive value of selected indicators in the prognosis of surgically resected SCLC patients. In the study, 177 SCLC patients undergoing surgical resection were ultimately included. Both univariate and multivariate Cox analysis revealed that incomplete postoperative adjuvant therapy emerged as an independent risk factor for adverse prognosis (p < 0.001, HR 2.96). Survival analysis revealed significantly superior survival among pN0-1 patients compared to pN2 patients (p < 0.0001). No significant difference in postoperative survival was observed between pN1 and pN0 patients (p = 0.062). Patients with postoperative stable disease (SD) exhibited lower levels of tumor inflammatory cells (TIC) (p = 0.0047) and IFN-γ expression in both area and intensity (p < 0.0001 and 0.0091, respectively) compared to those with postoperative progressive disease (PD). Conversely, patients with postoperative SD showed elevated levels of stromal inflammatory cells (SIC) (p = 0.0453) and increased counts of CD3+ and CD8+ cells (p = 0.0262 and 0.0330, respectively). Survival analysis indicated that high levels of SIC, along with low levels of IFN-γ+ cell area within tumor tissue, may correlate positively with improved prognosis in surgically resected SCLC (p = 0.017 and 0.012, respectively). In conclusion, the present study revealed that the patients with pT1-2N1M0 staging were a potential subgroup of SCLC patients who may benefit from surgery. Complete postoperative adjuvant therapy remains an independent factor promoting a better prognosis for SCLC patients undergoing surgical resection. Moreover, CD3, CD8, IFN-γ, TIC, and SIC may serve as potential indicators for predicting the prognosis of surgically resected SCLC.
Validation and Application of a Dried Blood Spot Amoxicillin Assay
Authors: Page-Sharp Madhu , Yoo Okhee , Salman Sam , Davis Timothy M. E. , Moore Brioni R. , Manning Laurens , Batty Kevin T.
Published: May 2024

Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK) investigations in situations where venous blood sampling is logistically and/or ethically challenging. The aim of this study was to establish, validate and demonstrate the application of a DBS amoxicillin assay for PK studies in vulnerable populations. The matrix effect, process efficiency (84–104%) and recovery (85–110%) of the liquid chromatography–mass spectrometry (LC–MS/MS) assay for amoxicillin in DBS was determined at 1, 10 and 100 µg/mL, and three different haematocrits. Thermal stability studies of amoxicillin in DBS were performed and a bridging study comprising 26 paired plasma and DBS samples was conducted in four healthy individuals. The limits of detection and quantification were 0.02 and 0.05 µg/mL for plasma and DBS amoxicillin assays, respectively. Accuracy and interday precision of amoxicillin in DBS (0.1–100 µg/mL) were 88–103% and 4.5–9.2%, respectively. At room temperature (22 °C) and 4 °C, amoxicillin was stable in DBS for ≈4 and 26 h, respectively. There was no degradation of amoxicillin in DBS at −20 °C for > 6 months. When comparing DBS and plasma collected from healthy volunteers, the slope of the Deming regression was 0.74. Amoxicillin CL/F estimates from DBS and plasma concentration data were 40.8 and 30.7 L/h/70 kg, respectively; V/F was 43.2 and 37.4 L/70 kg, respectively. In conclusion, amoxicillin can be reliably assayed from DBS in research studies but may have limited application in therapeutic drug monitoring. Due to poor stability at room temperature, amoxicillin DBS samples should be promptly dried and placed in frozen storage.
The association of resilience and physical activity in older adults: cross-sectional analyses from the NICOLA study
Authors: O’Doherty Maeve , Cunningham Conor , Neill Ruth D. , Tully Mark A.
Published: May 2024

Aim

As more of the world’s population are living longer, supporting the mental and physical health of older adults is becoming increasingly important in public health. Resilience is a dynamic process encompassing positive adaptation in the face of adverse experiences that would otherwise lead to poor outcomes. The aim of the study is to explore the association between physical activity and resilience in older adults.

Subject and methods

The data used in this study was taken from the results of the Self Completed Questionnaires and Computer Assisted Personal Interviews from the Northern Ireland Cohort for the Longitudinal Study of Ageing. A secondary analysis was conducted on a sample of 4040 participants to examine the association between resilience (Brief Resilience Scale) and on moderate/vigorous physical activity (International Physical Activity Questionnaire – Short Form) through chi-square and Mann–Whitney U tests and an ordinal regression being conducted.

Results

Data was included for 4040 participants, of whom 90% did not meet the recommended moderate physical activity guidelines. The findings of this study indicated that higher resilience levels are associated with higher levels of moderate and vigorous physical activity levels.

Conclusion

Worryingly, a large percentage of the older adult population are not sufficiently active and this is something that needs to be addressed. The findings suggest that with these low levels of physical activity, interventions should be created to target this population.
Development and Delphi consensus validation of the Medication-Related Fall screening and scoring tool
Authors: Saeed Dima , Carter Gillian , Miller Ruth , Darcy Carmel , Miller Karen , Madden Kevin , McKee Hilary , Agnew Jayne , Crawford Paula , Parsons Carole
Published: May 2024

Background

Falls are a significant public health problem and constitute a major cause of injuries and mortality. Risk factors for falls are multifactorial and include medication use.

Aim

To develop and investigate the content validity of the Medication-Related fall (MRF) screening and scoring tool.

Method

The MRF tool was developed from clinical practice guidelines addressing medication-related problems, and additional medications identified by specialist pharmacists across a region of the United Kingdom (Northern Ireland). Medication classes were categorised according to their ‘potential to cause falls’ as: high-risk (three points), moderate-risk (two points) or low-risk (one point). The overall medication-related falls risk for the patient was determined by summing the scores for all medications. The MRF was validated using Delphi consensus methodology, whereby three iterative rounds of surveys were conducted using SurveyMonkey®. Twenty-two experts from 10 countries determined their agreement with the falls risk associated with each medication on a 5-point Likert scale. Only medications with at least 75% of respondents agreeing or strongly agreeing were retained in the next round.

Results

Consensus was reached for 19 medications/medication classes to be included in the final version of the MRF tool; ten were classified as high-risk, eight as moderate-risk and one as low-risk.

Conclusion

The MRF tool is simple and has the potential to be integrated into medicines optimisation to reduce falls risk and negative fall-related outcomes. The score from the MRF tool can be used as a clinical parameter to assess the need for medication review and clinical interventions.
Energy-information trade-off induces continuous and discontinuous phase transitions in lateral predictive coding
Authors: Huang Zhen-Ye , Zhou Ruyi , Huang Miao , Zhou Hai-Jun
Published: May 2024

Lateral predictive coding is a recurrent neural network that creates energy-efficient internal representations by exploiting statistical regularity in sensory inputs. Here, we analytically investigate the trade-off between information robustness and energy in a linear model of lateral predictive coding and numerically minimize a free energy quantity. We observed several phase transitions in the synaptic weight matrix, particularly a continuous transition that breaks reciprocity and permutation symmetry and builds cyclic dominance and a discontinuous transition with the associated sudden emergence of tight balance between excitatory and inhibitory interactions. The optimal network follows an ideal gas law over an extended temperature range and saturates the efficiency upper bound of energy use. These results provide theoretical insights into the emergence and evolution of complex internal models in predictive processing systems.
Shape completion in the dark: completing vertebrae morphology from 3D ultrasound
Authors: Gafencu Miruna-Alexandra , Velikova Yordanka , Saleh Mahdi , Ungi Tamas , Navab Nassir , Wendler Thomas , Azampour Mohammad Farid
Published: May 2024

Purpose

Ultrasound (US) imaging, while advantageous for its radiation-free nature, is challenging to interpret due to only partially visible organs and a lack of complete 3D information. While performing US-based diagnosis or investigation, medical professionals therefore create a mental map of the 3D anatomy. In this work, we aim to replicate this process and enhance the visual representation of anatomical structures.

Methods

We introduce a point cloud-based probabilistic deep learning (DL) method to complete occluded anatomical structures through 3D shape completion and choose US-based spine examinations as our application. To enable training, we generate synthetic 3D representations of partially occluded spinal views by mimicking US physics and accounting for inherent artifacts.

Results

The proposed model performs consistently on synthetic and patient data, with mean and median differences of 2.02 and 0.03 in Chamfer Distance (CD), respectively. Our ablation study demonstrates the importance of US physics-based data generation, reflected in the large mean and median difference of 11.8 CD and 9.55 CD, respectively. Additionally, we demonstrate that anatomical landmarks, such as the spinous process (with reconstruction CD of 4.73) and the facet joints (mean distance to ground truth (GT) of 4.96 mm), are preserved in the 3D completion.

Conclusion

Our work establishes the feasibility of 3D shape completion for lumbar vertebrae, ensuring the preservation of level-wise characteristics and successful generalization from synthetic to real data. The incorporation of US physics contributes to more accurate patient data completions. Notably, our method preserves essential anatomical landmarks and reconstructs crucial injections sites at their correct locations.
Depth over RGB: automatic evaluation of open surgery skills using depth camera
Authors: Zuckerman Ido , Werner Nicole , Kouchly Jonathan , Huston Emma , DiMarco Shannon , DiMusto Paul , Laufer Shlomi
Published: May 2024

Purpose

In this paper, we present a novel approach to the automatic evaluation of open surgery skills using depth cameras. This work is intended to show that depth cameras achieve similar results to RGB cameras, which is the common method in the automatic evaluation of open surgery skills. Moreover, depth cameras offer advantages such as robustness to lighting variations, camera positioning, simplified data compression, and enhanced privacy, making them a promising alternative to RGB cameras.

Methods

Experts and novice surgeons completed two simulators of open suturing. We focused on hand and tool detection and action segmentation in suturing procedures. YOLOv8 was used for tool detection in RGB and depth videos. Furthermore, UVAST and MSTCN++ were used for action segmentation. Our study includes the collection and annotation of a dataset recorded with Azure Kinect.

Results

We demonstrated that using depth cameras in object detection and action segmentation achieves comparable results to RGB cameras. Furthermore, we analyzed 3D hand path length, revealing significant differences between experts and novice surgeons, emphasizing the potential of depth cameras in capturing surgical skills. We also investigated the influence of camera angles on measurement accuracy, highlighting the advantages of 3D cameras in providing a more accurate representation of hand movements.

Conclusion

Our research contributes to advancing the field of surgical skill assessment by leveraging depth cameras for more reliable and privacy evaluations. The findings suggest that depth cameras can be valuable in assessing surgical skills and provide a foundation for future research in this area.
Treat and release: an observational study of non-conveyed high-acuity dispatches in a Danish emergency medical system
Authors: Wolthers Signe Amalie , Mikaelsson Tor Jerker , Holgersen Mathias Geldermann , Blomberg Stig Nikolaj Fasmer , Andersen Lars Bredevang , Mikkelsen Søren , Christensen Helle Collatz
Published: May 2024

Non-conveyance refers to the practice of treating a patient on-site without transporting them to a medical facility. It may decrease unnecessary hospital transfers and improve patient satisfaction. Nonetheless, ensuring patient safety remains paramount. The objective of the study was to assess admission to hospital and mortality in non-conveyed patients. This population-based cohort study included all high-acuity dispatches in Region Zealand, Denmark between 2019 and 2022. The primary outcome was admission within 48 h, and the secondary outcome was 30-day mortality. Descriptive statistical analyses were conducted, and logistic regression models were used to estimate adjusted odds ratios and 95% confidence intervals. A non-conveyance rate of 14% was identified in 95,238 transports. Admission within 48 h was seen in 22% of non-conveyed patients vs. 95% in conveyed patients, p < 0.001. The adjusted analysis showed a decreased likelihood of admission within 48 h within non-conveyed patients, with an aOR of 0.01 95% CI (0.01–0.01). Non-conveyed patients had a crude 30-day mortality rate of 2 vs. 6% among conveyed patients, p < 0.001. The adjusted analysis showed an increased likelihood of 30-day mortality in non-conveyed patients with an odds ratio of 1.21, 95% CI (1.05–1.40). Non-conveyed patients constitute a substantial proportion of patients assessed by ambulances following high-acuity dispatch. Less than one in four non-conveyed patients were admitted within 48 h. Despite the low crude mortality in this study, an increased likelihood of mortality was found within the non-conveyed population. However, additional investigation is warranted in future research.
Simulation of process forces and topographical characteristics of single grains in microfinishing processes
Authors: Heining Ines , Bergmann Jim A. , Tilger Meik , Biermann Dirk , Wiederkehr Petra
Published: May 2024

Honing operations, e.g. microfinishing, are resulting in high quality surfaces with a roughness values, e.g., average roughness Ra, of only a few micro- to nanometer [1]. The simulation of honing processes can be beneficial to reduce experimental effort in terms of determining suitable process parameters for such processes. Various aspects of the finishing process can be investigated with the aid of process models, such as tool wear, tool life, the resulting surface quality or shape deviation. In addition, process simulations can be used to assist in the design of components with regard to desired functional properties. In order to model processes with such high accuracy, it is necessary to be aware of process influences on a microscropic scale. Such influences can be analyzed separately, for instance, by means of analogy experiments to reduce the complexity and dependencies of the occurring effects. In this work, a process force model was developed based on single-grain scratch tests, which takes into account the process-inherent kinematic variations. The occurring single grain forces in dependence of the orientation of the grains and in relation to the cutting direction were analyzed and modeled. This is important for a further analysis of the influences on tool wear to increase the accuracy of corresponding models.
Relation Between Exposure to Tobacco Smoke Assessed by Serum Cotinine Concentration and Questionnaire Method, and Serum Renalase Concentration—the Importance of the Coexistence of Arterial Hypertension and Other Cardiovascular Diseases
Authors: Żórawik Aleksandra , Hajdusianek Wojciech , Kusnerż Agnieszka , Markiewicz-Górka Iwona , Jaremków Aleksandra , Martynowicz Helena , Pawlas Krystyna , Mazur Grzegorz , Poręba Rafał , Gać Paweł
Published: May 2024

Exposure to tobacco smoke (ETS) is one of the main risk factors for cardiovascular disease (CVD). Renalase is a protein that may play a role in the pathogenesis of CVD. The aim of the study was to assess the relationship between ETS and serum renalase concentration. A group of 109 patients was recruited for this study (49.7 ± 14.7 years). In accordance with the questionnaire, patients were divided into the following subgroups: subgroup A– declaring themselves active smokers (n = 36), subgroup B– declaring themselves non-smokers and exposed to environmental tobacco smoke (n = 35), subgroup C– declaring themselves non-smokers and not exposed to environmental tobacco smoke (n = 38). The same patients were divided based on cotinine concentration into the following subgroups: subgroup D– active smokers (n = 42), subgroup E– non-smokers exposed to environmental tobacco smoke (n = 66), and subgroup F– non-smokers not exposed to environmental tobacco smoke (n = 1). Serum cotinine concentration and serum renalase concentration were measured using ELISA tests. Serum renalase concentration was statistically significantly higher in subgroup C than in subgroups A and B and in subgroup E and F than in D. There was a negative correlation between serum cotinine concentration and serum renalase concentration (r = −0.41, p < 0.05). Regression analysis showed that higher BMI, higher diastolic blood pressure, coronary artery disease and higher serum cotinine concentration are independent risk factors of lower serum renalase concentration. The questionnaire method of assessing exposure to tobacco smoke was characterized by high sensitivity, but only moderate specificity, especially in terms of assessing environmental exposure to tobacco smoke. In summary, the study showed an independent relationship between exposure to tobacco smoke and lower serum renalase concentration.
GH provocative tests stimulate the growth in children with idiopathic short stature
Authors: Tortora Anna , Marotta Vincenzo , Izzo Giulia , Rocco Domenico , Clemente Gennaro , Vitale Mario
Published: May 2024

Context

Growth hormone (GH) deficiency in a child with short stature is diagnosed by GH secretion provocative tests. When the test response is considered adequate, the short stature is considered idiopathic (ISS).

Objective

To determine the effect of GH provocative tests on the growth rate in children with idiopathic short stature.

Design

Children with short stature with a normal response to at least one GH provocative test were enrolled. Height and growth velocity were measured prior to and after stimulus tests during the follow-up.

Methods

Height, mid-parental height, body weight, and body mass index were measured. The height and growth rate were converted to percentiles and Standard Deviation Scores (SDS) using reference ranges standardized by age and sex. GH provocative tests employed arginine or clonidine as secretagogues.

Results

Fourty-six children of both genders were enrolled. In thirty-six children, height was measured at the time of testing and on an average time prior to and after the tests of 210 days and 180 days respectively. After testing the children displayed a 3.4-fold increase in their estimated 90-day growth rate. The median (inter-quartile range, IQR) 90 days growth of children pre-and post-tests were 0.7 (0.2–1.0) cm and 2.4 (1.7–3.1) cm respectively with a mean 3,4-fold increase (p < 0.0001). The median (IQR) 90 days growth of children pre- and post-tests calculated as standard deviation scores (SDS) were −4.0 (−5.4–−2.1) SDS and 0.1 (−1.9–1.4) SDS respectively (p < 0.0001). Ten children with ISS were observed for about 5 months before the GH provocative tests. A small increase in the growth rate was seen only in 2 out of 10 children before testing while it increased in all of them after the tests. The difference in the median growth rate at the first and the second observation was not significant (p = 0.219).

Conclusions

Two sequential somatotropic axis provocative tests increase the growth rate in children with idiopathic short stature. The duration of this effect is yet to be determined.
Geospatial technologies for landslide monitoring: a case study of Sighetu Marmației, Romania
Authors: Kalmar Tiberiu Mihai , Dîrja Marcel , Rădulescu Adrian Traian G. M. , Măran Petru Daniel , Rădulescu Gheorghe M. T. , Nychvyd Mariya , Kalynych Ivan , Rădulescu Virgil Mihai G. M. , Zaharia Gelu , Danku Gelu
Published: May 2024

Landslides are a significant geological phenomenon with the potential for catastrophic consequences. There are numerous potential causes of landslides, including both natural and man-made ones. Their growing frequency raises alarm due to the often catastrophic consequences of these events. The monitoring of regions prone to landslides is a multifaceted undertaking that involves the use of several technologies and approaches, such as geospatial technology and modeling. The primary objective of this work is to construct a spatial analysis model for a region in north-western Romania that is susceptible to landslides. A case study was conducted to estimate the susceptibility of landslides in a monitored region located near Sighetu Marmației, Romania. To achieve this objective, a combination of several technologies and approaches were used, such as remote sensing, land surveying, aerial photogrammetry, geographic information systems, and spatial modeling. The research region underwent landslide susceptibility evaluation by processing geo-information data using Geographic Information Systems (GIS) and developing a prediction model based on the MaxEnt (Maximum Entropy) approach. The research’s distinctive contribution is integrating geo-information data acquired from the hazardous site utilizing geomatics methods into a novel geo-monitoring system. The research offers valuable insights into the monitoring of landslides, adding to the current body of literature by introducing an expanded paradigm. The study’s theoretical and practical implications might be valuable for professionals, local authorities, emergency response agencies, and other parties involved in mitigating the danger of landslides.