bluuebunny/crossref_metadata_2025 huggingface dataset:
Bile acid diarrhoea and metabolic changes after cholecystectomy: a prospective case-control study
Authors: Farrugia Alexia , Williams Nigel , Khan Saboor , P. Arasaradnam Ramesh
Published: August 2024

Introduction

Bile acid diarrhoea (BAD) can occur due to disruption to the enterohepatic circulation such as following cholecystectomy. However, the mechanism behind this is as yet unknown. The aim of this study was to determine the rate of post-cholecystectomy diarrhoea and to assess whether FGF19 within the gallbladder was associated with the development of BAD.

Methods

This was a prospective case-control study in which patients were assessed pre- and post- cholecystectomy (study group) and compared with patients also having laparoscopic surgery but not cholecystectomy (control group). Their bowel habits and a GIQLI questionnaire was performed to compare the pre- and post-operative condition of the two groups. Gallbladder tissue sample was tested for FGF19 and PPARα in the study group patients. A subset had serum lipid levels, FGF19 and C4 measurements.

Results

Gallbladder PPAR α was found to have a significant correlation with stool consistency, with the lower the PPARα concentration the higher the Bristol stool chart number (i.e. looser stool). There were no significant correlation when assessing the effect of gallbladder FGF19 concentration on bowel habit, stool consistency, lipid levels, BMI or smoking. The study group showed a significant increase in triglycerides post-operatively, however there were no changes in cholesterol, HDL and LDL levels. Correlation of the increased triglyceride levels with stool consistency and frequency showed no significant results

Discussion and conclusion

We did not find any direct evidence that FGF19 levels within the gallbladder impact the development of post-cholecystectomy diarrhoea. There was however a significant increase in triglycerides postoperatively. There was also no correlation of bowel habits with PPARα suggesting the observed rise is independent of this pathway. Further work is required particularly relating to the gut microbiome to further investigate this condition.
Perinatal outcomes after a prenatal diagnosis of a fetal copy number variant: a retrospective population-based cohort study
Authors: Pynaker Cecilia , McCoy Jacqui , Halliday Jane , Lewis Sharon , Amor David J. , Walker Susan P. , Hui Lisa ,   On behalf of the PALM cohort study group, Kennedy Joanne , Norris Fiona , Gugasyan Lucy , Brown Emma , Svobodova Suzanne , Regan Matthew , Kincaid Helen , Vasudevan Anand , Fawcett Susan , Graetz Melissa , Said Joanne , Begg Lisa , Yuen Nicole , Frawley Natasha , Masson Geraldine
Published: August 2024

Background

There are no established guidelines for the follow up of infants born after a prenatal diagnosis of a genomic copy number variant (CNV), despite their increased risk of developmental issues. The aims of this study were (i) to determine the perinatal outcomes of fetuses diagnosed with and without a CNV, and (ii) to establish a population-based paediatric cohort for long term developmental follow up.

Methods

An Australian state-wide research database was screened for pregnant individuals who had a prenatal chromosomal microarray (CMA) between 2013–2019 inclusive. Following linkage to laboratory records and clinical referrer details, hospital records were manually reviewed for study eligibility. Eligible participants were mother–child pairs where the pregnancy resulted in a livebirth, the mother was able to provide informed consent in English (did not require a translator) and the mother was the primary caregiver for the child at hospital discharge after birth. Research invitations were sent by registered post at an average of six years after the prenatal diagnostic test. Statistical analysis was performed in Stata17.

Results

Of 1832 prenatal records examined, 1364 (74.5%) mother–child pairs were eligible for recruitment into the follow up cohort. Of the 468 ineligible, 282 (60.3%) had ‘no live pregnancy outcome’ (209 terminations of pregnancy (TOP) and 73 miscarriages, stillbirths, and infant deaths), 157 (33.5%) required a translator, and 29 (6.2%) were excluded for other reasons. TOP rates varied by the type of fetal CNV detected: 49.3% (109/221) for pathogenic CNVs, 18.2% (58/319) for variants of uncertain significance and 3.3% (42/1292) where no clinically significant CNV was reported on CMA. Almost 77% of invitation letters were successfully delivered (1047/1364), and the subsequent participation rate in the follow up cohort was 19.2% (201/1047).

Conclusions

This study provides Australia’s first population-based data on perinatal outcomes following prenatal diagnostic testing with CMA. The relatively high rates of pregnancy loss for those with a prenatal diagnosis of a CNV presented a challenge for establishing a paediatric cohort to examine long term outcomes. Recruiting a mother–child cohort via prenatal ascertainment is a complex and resource-intensive process, but an important step in understanding the impact of a CNV diagnosis in pregnancy and beyond.

Trial registration

ACTRN12620000446965p; Registered on April 6, 2020.
Impact of moderate-to-high-suicide-intent in major depressive disorder: a retrospective cohort study on patient characteristics and healthcare resource utilisation in England
Authors: Denee Tom , Kerr Cicely , Richards Sarah , Dennis Natalie , Foix-Colonier Astrid , Fischer Claire , Larkin Fintan
Published: August 2024

Background

Major depressive disorder (MDD) is a disabling mental illness that can affect all aspects of daily life and is a leading cause of healthcare resource utilisation (HCRU).

Aims

We aimed to characterise patients with MDD with moderate-to-high-suicide-intent, compare their HCRU to patients with MDD without moderate-to-high-suicide-intent, and better understand their patient pathways.

Methods

This retrospective cohort study used data collected from primary care electronic health records from Clinical Practice Research Datalink (CPRD), linked to Hospital Episode Statistics, Mental Health Services Data Set, and Office for National Statistics in England. Adults diagnosed with ≥ 1 MDD diagnosis between 04/2007 and 11/2015 were categorised by suicide intent.

Results

307,476 patients with MDD were included (294,259 patients without moderate-to-high-suicide-intent and 13,217 with moderate-to-high-suicide-intent). Patients with MDD with moderate-to-high-suicide-intent were younger on average (39.0 vs. 44.8 years) and included a lower percentage of females (58% vs. 65%) compared to patients without moderate-to-high-suicide-intent. HCRU was greater among patients with moderate-to-high-suicide-intent than patients without moderate-to-high-suicide-intent during the first follow-up year for general practitioner consultations (38.5 vs. 29.4), psychiatric outpatient visits (1.5 vs. 0.1), psychiatrist visits (3.6 vs. 0.3), emergency visits (1.5 vs. 0.3), and hospitalisations (86% vs. 26%). Overall, 56% of patients with moderate-to-high-suicide-intent had an antidepressant prescription within 30 days from the initial moderate-to-high-suicide-intent.

Conclusions

Patients with MDD and moderate-to-high-suicide-intent were younger, included more males and incurred greater HCRU than those without moderate-to-high-suicide-intent. These results suggest a greater need for effective medical care and appropriate treatments for patients with moderate-to-high-suicide-intent, which could help reduce associated symptoms, mortality, and HCRU.
Risk and protective factors associated with substance use among Puerto Rican youths after Hurricane María: a cross-sectional study
Authors: Gonzalez Juan Carlos , Feinberg Daniel K. , Stewart Regan W. , Young John , Orengo-Aguayo Rosaura
Published: August 2024

Background

Identifying factors associated with post-disaster youth substance use is a crucial element of developing evidence-based prevention and intervention efforts. Hurricane María struck Puerto Rico in September of 2017 and the wide-spread impact from this disaster, including exposure to trauma, displacement, and disrupted social supports had the potential to negatively impact levels of substance use among youth across the archipelago. However, post-disaster substance use remains under-investigated in this context. The current study sought to identify risk and protective factors associated with substance use among Puerto Rican youth in the aftermath of Hurricane Maria.

Methods

Cross-sectional, secondary data analyses were conducted using school-based survey data collected at all schools in Puerto Rico between February 1 and June 29, 2018 (5–9 months after Hurricane María). Social supports, substance use, and trauma symptoms were assessed. An ordinal regression analysis was conducted to identify student factors associated with greater likelihood of post-disaster substance use.

Results

A total of 36,485 participants (50.7% female, grades 7–12), were included in an ordinal regression analysis that compared the likelihood of respondents endorsing high, low, or no substance use after Hurricane María based on reported adult social support, counselor/teacher social support, peer social support, ptsd symptomatology, and gender. Findings showed that, when compared to students that endorsed low or no substance use, those who reported having adult social support demonstrated a 58% reduction in odds (OR = 0.42, 95% CI: 0.34-0.53) of reporting high substance use after Hurricane María, while students who reported having teacher/counselor social support demonstrated a 21% reduction in odds (OR = 0.79, 95% CI: 0.69-0.89) of reporting high substance use. Additionally, those that reported having peer social support demonstrated a 31% increase in odds (OR = 1.31, 95% CI: 1.10 to 1.58) of reporting higher substance use, compared to those that reported low or no substance use.

Conclusions

While social support was generally protective, prevention efforts to build positive family and community connections may be indicated. Evidence-based school screenings of substance use and trauma may help direct intervention to those most at risk for co-occurring issues.
Frequency of benign tumors after partial nephrectomy and the association between malignant tumor findings and preoperative clinical parameters
Authors: Lounová Veronika , Študent, Vladimír , Purová Dana , Hartmann Igor , Vidlář Aleš , Študent Vladimír
Published: August 2024

Background

Partial nephrectomy (PN) has become the dominant treatment modality for cT1 renal tumor lesions. Tumors suspected of malignant potential are indicated for surgery, but some are histologically classified as benign lesions after surgery. This study aims to analyze the number of benign findings after PN according to definitive histology and to evaluate whether there is an association between malignant tumor findings and individual factors.

Methods

The retrospective study included 555 patients who underwent open or robotic-assisted PN for a tumor in our clinic from January 2013 to December 2020. The cohort was divided into groups according to definitive tumor histology (malignant tumors vs. benign lesions). The association of factors (age, sex, tumor size, R.E.N.A.L.) with the malignant potential of the tumor was further evaluated.

Results

In total, 462 tumors were malignant (83%) and 93 benign (17%). Of the malignant tumors, 66% were clear-cell RCC (renal cell carcinoma), 12% papillary RCC, and 6% chromophobe RCC. The most common benign tumor was oncocytoma in 10% of patients, angiomyolipoma in 2%, and papillary adenoma in 1%. In univariate analysis, there was a higher risk of malignant tumor in males (OR 2.13, 95% CI 1.36–3.36, p = 0.001), a higher risk of malignancy in tumors larger than 20 mm (OR 2.32, 95% CI 1.43–3.74, p < 0.001), and a higher risk of malignancy in tumors evaluated by R.E.N.A.L. as tumors of intermediate or high complexity (OR 2.8, 95% CI 1.76–4.47, p < 0.001). In contrast, there was no association between older age and the risk of malignant renal tumor (p = 0.878).

Conclusions

In this group, 17% of tumors had benign histology. Male sex, tumor size greater than 20 mm, and intermediate or high R.E.N.A.L. complexity were statistically significant predictors of malignant tumor findings.
Comparison of the biomechanical effects of the post-core crown, endocrown and inlay crown after deep margin elevation and its clinical significance
Authors: Wu Feng , Su Xiaomin , Shi Yue , Bai Juan , Feng Jing , Sun Xilin , Wang Xuanqi , Wang Hongyan , Wen Jiayu , Kang Jie
Published: August 2024

Background

The purpose of this in vitro study was to compare and evaluate the stress distribution of maxillary first premolar residual crowns restored with post-core crowns, endocrowns and inlay crowns after deep margin elevation, to explore the fitting restoration for residual crowns using finite element analysis.

Methods

A healthy complete right maxillary first premolar from a male adult was scanned by cone beam computed tomography (CBCT). The finite element model of the tooth was established by reverse engineering software such as Mimics, Geomagic and Hypermesh. On this basis, the residual crown model after deep margin elevation was made, and the experimental group models were divided into three groups, those restored with post core crowns, endocrowns and inlay crowns. Vertical and oblique static loads were applied to the experimental models to simulate the force on the tooth during mastication (the loading position was located in the central fossa of the occipital surface, and the load was 100 N) using Abaqus software.

Results

The peak value and distribution of von Mises stress in each part of the experimental model were observed. After deep margin elevation, the peak dentin von Mises stresses were lower than the tensile strength of normal dentin in the post-core crown, endocrown, and inlay crown groups; the lowest stress results were found in the post-core crown group for the dentin, restoration, enamel, and deep margin elevation (DME) layers under vertical and oblique loading. In terms of stress distribution clouds, the peak stresses in the dentin tissue were located in the apical 1/3 of the root after postcore crown restorations for both loads, while stress concentrations were evident in the cervical and root areas after endocrown and inlay crown restorations; regardless of the load and restoration method, the corresponding stress concentration areas appeared at the junction of the DME and dentin tissue at the loading site of the restorations;

Conclusions

Post-core crowns, endocrowns and inlay crowns can be used to restore residual crowns after deep margin elevation, and post-core crowns can better protect the residual tooth tissue.
Evaluation of the effect of thermocycling on the trueness and precision of digitally fabricated complete denture bases
Authors: Zeidan Ahmed Abd El-latif , Helal Mohamed Ahmed
Published: August 2024

Background

While many denture base materials are currently available on the market, little data exists regarding their dimensional stability after exposure to the oral environment. This study aimed to evaluate the effect of thermocycling on the trueness and precision of milled, 3-dimensional (3D)-printed, and conventional digitally fabricated complete denture bases (CDBs).

Methods

A completely edentulous maxillary stone model was scanned to generate a standard tessellation language (STL) file; this was imported into metal-milling-machine software (Redon Hybrid CAD-CAM metal milling machine, Redon, Turkey) to produce a metal model for fabricating 30 CDBs. These were divided into three groups (n = 10 in each) according to the construction technique: group 1, CAD-CAM milled CDBs; group 2, 3D-printed CDBs; and group 3, conventional compression molded CDBs. All CDBs were scanned after fabrication and evaluated before and after thermocycling using superimposition. The data were analyzed using a one-way ANOVA, Tukey’s post hoc test, and a paired t-test.

Results

The level of trueness between the CAD-CAM milled, 3D-printed, and compression molded CDBs showed significant differences before and after thermocycling (P < 0.05). Group 1 showed the highest degree of trueness before and after thermocycling, group 3 exhibited a higher degree of trueness than group 2 before thermocycling, and group 2 had a higher degree of trueness than group 3 after thermocycling. There was a significant difference in the precision for each CDB type before and after thermocycling (P < 0.05).

Conclusion

The trueness of the CAD-CAM milling system in complete denture (CD) fabrication is superior to that of the 3D printing and conventional compression molding systems before and after thermocycling. Thermocycling had a significant effect on the precision of all CDB types. The compression molding system in CD construction is the most negatively affected via thermocycling with regard to the measures of trueness and precision.

Clinical trial number

Not applicable, no human participants were involved.
“Killing two birds with one stone” – a qualitative study on women’s perspectives on the dual prevention pill in Johannesburg, South Africa
Authors: Tenza Siyanda , Mampuru Lydia , Moji Mpho , Zulu Sihle , Begg Lorna , Bruce Irene V. , Reddy Krishnaveni , Friedland Barbara A. , Palanee-Phillips Thesla , Mathur Sanyukta
Published: August 2024

Background

HIV incidence remains high in South Africa, with ~ 60% of all new HIV infections among adolescent girls and women (Country factsheets HIV and AIDS Estimates, 2022). Oral pre-exposure prophylaxis (PrEP), approved for HIV prevention in South Africa since 2015, is hampered by low uptake and adherence, particularly among adolescent girls and young women (AGYW). Combining oral PrEP with oral contraceptives could increase PrEP uptake, persistence and address unmet needs for contraception. We investigated the acceptability of a dual prevention pill (DPP), combining oral PrEP and a combined oral contraceptive (COC) for HIV and pregnancy prevention among women in Johannesburg, South Africa.

Methods

Between March-July 2021, we conducted 12 focus group discussions (FGDs) with adolescent girls and women (n = 74) aged 16–40 stratified by ages (16–17, 18–24, 25–40), half of whom were COC users. We explored adolescent girls and women’s opinions about the DPP concept, existing HIV and pregnancy prevention options, and input on perceived facilitators and barriers to DPP use. FGDs were conducted in English or isiZulu, using a standardized interview guide. FGDs were audio-recorded, transcribed to English and analyzed using ethnographic content analysis.

Results

The majority viewed the DPP favorably as a multipurpose option preventing unplanned pregnancy and HIV. Most saw it as a convenient “two-in-one” solution, requiring one clinic visit for both PrEP and COCs. AGYW were viewed as the most likely to benefit from the DPP due to the likelihood of multiple partners and unplanned sex, possibly preventing school dropout from unplanned pregnancy or HIV acquisition. The DPP was perceived to be more reliable than condoms, especially when condom negotiation is limited. Benefits were also seen by participants in rape cases, protecting against pregnancy and HIV. DPP use barriers included side effect concerns, unsupportive partners and judgmental healthcare providers.

Conclusions/significance

The DPP was perceived as acceptable for HIV and pregnancy prevention to AGYW in Johannesburg and its dual indications helpful in supporting improved PrEP uptake and persistence. DPP implementation programs need to consider solutions to potential barriers, like education on DPP benefits, coupled with reliable side effect support and healthcare provider sensitization as part of routine sexual health services to encourage uptake and adherence.
Who learns more: the impact of dual-player and single-player modes in a serious game on dental students’ factual knowledge
Authors: Krause Felix , Horn Ben , Braun Andreas , Fedrowitz Sebastian , Bell Laura , Lemos Martin
Published: August 2024

Background

The use of serious games in medical education provides a bridge between rapidly developing technology and traditional health-care teaching. Building on a promising web-based serious game for reviewing and acquiring factual knowledge in dental education, the present study investigated the benefits of a dual-player mode and various game options for enhancing knowledge gain and study motivation.

Methods

Before the intervention, students’ dental knowledge and game experience were assessed using a pre-knowledge test and questionnaire-based self-assessment. Students in the clinical study phase (n = 57) were stratified based on prior knowledge and gender and then randomly assigned to two groups, with two player modes: single player (SP) and dual player (DP). In the SP group, each participant played alone, whereas in the DP group, the participants played against a previously determined peer. For a period of 4 weeks, the students were able to playfully acquire knowledge from the field of operative dentistry using METIS, a serious game application with three different game options (Marathon, Sprint, and Time). After the intervention phase, both groups completed a post-knowledge test. The usability of the serious game was evaluated with a self-assessment questionnaire.

Results

The competitive game mode (DP mode; M = 8.92, SD = 1.85) resulted in an increase in the factual knowledge test that was a mean of 2.49 points higher than the SP mode (M = 5.89, SD = 2.19; p < 0.001). The DP group also found the game significantly more helpful for learning (p = 0.04) and engaged more with the teaching content because of the app (p = 0.04). Overall, the usability of METIS was rated as excellent, and students successfully improved their knowledge of dentistry after game play with both game modes (SP, DP, p < 0.001), with the game option “Marathon,” which involves playing the largest number of questions, being the most preferred.

Conclusions

These results suggest that serious games such as METIS are a suitable educational medium for increasing students’ knowledge and interest in the field, and that competition with peers provides even greater motivation to engage with the learning content.
Prediction of midpalatal suture maturation stage based on transfer learning and enhanced vision transformer
Authors: Tang Haomin , Liu Shu , Tan Weijie , Fu Lingling , Yan Ming , Feng Hongchao
Published: August 2024

Background

Maxillary expansion is an important treatment method for maxillary transverse hypoplasia. Different methods of maxillary expansion should be carried out depending on the midpalatal suture maturation levels, and the diagnosis was validated by palatal plane cone beam computed tomography (CBCT) images by orthodontists, while such a method suffered from low efficiency and strong subjectivity. This study develops and evaluates an enhanced vision transformer (ViT) to automatically classify CBCT images of midpalatal sutures with different maturation stages.

Methods

In recent years, the use of convolutional neural network (CNN) to classify images of midpalatal suture with different maturation stages has brought positive significance to the decision of the clinical maxillary expansion method. However, CNN cannot adequately learn the long-distance dependencies between images and features, which are also required for global recognition of midpalatal suture CBCT images. The Self-Attention of ViT has the function of capturing the relationship between long-distance pixels of the image. However, it lacks the inductive bias of CNN and needs more data training. To solve this problem, a CNN-enhanced ViT model based on transfer learning is proposed to classify midpalatal suture CBCT images. In this study, 2518 CBCT images of the palate plane are collected, and the images are divided into 1259 images as the training set, 506 images as the verification set, and 753 images as the test set. After the training set image preprocessing, the CNN-enhanced ViT model is trained and adjusted, and the generalization ability of the model is tested on the test set.

Results

The classification accuracy of our proposed ViT model is 95.75%, and its Macro-averaging Area under the receiver operating characteristic Curve (AUC) and Micro-averaging AUC are 97.89% and 98.36% respectively on our data test set. The classification accuracy of the best performing CNN model EfficientnetV2_S was 93.76% on our data test set. The classification accuracy of the clinician is 89.10% on our data test set.

Conclusions

The experimental results show that this method can effectively complete CBCT images classification of midpalatal suture maturation stages, and the performance is better than a clinician. Therefore, the model can provide a valuable reference for orthodontists and assist them in making correct a diagnosis.
Analysing the intra and interregional components of spatial accessibility gravity model to capture the level of equity in the distribution of hospital services in Italy: do they influence patient mobility?
Authors: Pecoraro Fabrizio , Cellini Marco , Luzi Daniela , Clemente Fabrizio
Published: August 2024

Background

An equal distribution of hospital structures represents an important factor to achieve Universal Health Coverage. Generally, the most diffused approach to measure the potential availability to healthcare is the provider-to-population ratio based on the number of beds or professionals. However, this approach considers only the availability of resources provided at regional or local level ignoring the spatial accessibility of interregional facilities that are particularly accessed by patients living at the borders. Aim of this study is to outline the distribution of the intra and interregional services in Italy to capture the level of equity across the country. Moreover, it explores the impact of the accessibility to these resources on interregional patient’s mobility to receive care.

Methods

To compute spatial accessibility, we propose an alternative approach that applies the enhanced two-step floating catchment area (ESFCA) to capture the level of attraction of intra and interregional hospitals to a given population. Moreover, the adoption of process and outcome indices captured to what extent the quality of structures influenced patients in choosing services located inside or outside their region of residence.

Results

The study confirms that there is an unequal distribution of high-quality resources at regional and national level with a high level of inequality in the availability and accessibility of quality resources between the north and south part of Italy. This is particularly true considering the accessibility of intraregional resources in the southern part of the country that clearly influences patient choice and contribute to a significant cross border passive mobility to northern regions. This is confirmed by an econometric model that showed a significant effect of spatial accessibility with the propensity of patients of travel from the region of residence to receive care.

Conclusions

The analysis of intra and interregional components of spatial accessibility may contribute to identify to what extent patients are willing to travel outside their region of residence to access to care services. Moreover, it can contribute to gain a deeper understanding of the allocation of health resources providing input for policy makers on the basis of the principles of service accessibility in order to contain patient mobility.
Artificial intelligence in COPD CT images: identification, staging, and quantitation
Authors: Wu Yanan , Xia Shuyue , Liang Zhenyu , Chen Rongchang , Qi Shouliang
Published: August 2024

Chronic obstructive pulmonary disease (COPD) stands as a significant global health challenge, with its intricate pathophysiological manifestations often demanding advanced diagnostic strategies. The recent applications of artificial intelligence (AI) within the realm of medical imaging, especially in computed tomography, present a promising avenue for transformative changes in COPD diagnosis and management. This review delves deep into the capabilities and advancements of AI, particularly focusing on machine learning and deep learning, and their applications in COPD identification, staging, and imaging phenotypes. Emphasis is laid on the AI-powered insights into emphysema, airway dynamics, and vascular structures. The challenges linked with data intricacies and the integration of AI in the clinical landscape are discussed. Lastly, the review casts a forward-looking perspective, highlighting emerging innovations in AI for COPD imaging and the potential of interdisciplinary collaborations, hinting at a future where AI doesn’t just support but pioneers breakthroughs in COPD care. Through this review, we aim to provide a comprehensive understanding of the current state and future potential of AI in shaping the landscape of COPD diagnosis and management.
Impact of radiomics features, pulmonary emphysema score and muscle mass on the rate of pneumothorax and chest tube insertion in CT-guided lung biopsies
Authors: Leonhardi Jakob , Dahms Ulrike , Schnarkowski Benedikt , Struck Manuel Florian , Höhn Anne-Kathrin , Krämer Sebastian , Ebel Sebastian , Prasse Gordian , Frille Armin , Denecke Timm , Meyer Hans-Jonas
Published: August 2024

Iatrogenic pneumothorax is a relevant complication of computed tomography (CT)-guided percutaneous lung biopsy. The aim of the present study was to analyze the prognostic significance of texture analysis, emphysema score and muscle mass derived from CT-imaging to predict postinterventional pneumothorax after CT-guided lung biopsy. Consecutive patients undergoing CT-guided percutaneous lung biopsy between 2012 and 2021 were analyzed. Multivariate logistic regression analysis included clinical risk factors and CT-imaging features to detect associations with pneumothorax development. Overall, 479 patients (178 females, mean age 65 ± 11.7 years) underwent CT-guided percutaneous lung biopsy of which 180 patients (37.5%) developed pneumothorax including 55 patients (11.5%) requiring chest tube placement. Risk factors associated with pneumothorax were chronic-obstructive pulmonary disease (COPD) (p = 0.03), age (p = 0.02), total lung capacity (p < 0.01) and residual volume (p = 0.01) as well as interventional parameters needle length inside the lung (p < 0.001), target lesion attached to pleura (p = 0.04), and intervention duration (p < 0.001). The combined model demonstrated a prediction accuracy of the occurrence of pneumothorax with an AUC of 0.78 [95%CI: 0.70–0.86] with a resulting sensitivity 0.80 and a specificity of 0.66. In conclusion, radiomics features of the target lesion and the lung lobe CT-emphysema score are predictive for the occurrence of pneumothorax and need for chest insertion after CT-guided lung biopsy.
Dipeptide PA3264 derived from rare and endangered Squama Manis is a novel bioactive peptide for the treatment of triple-negative breast cancer
Authors: Hou Xiaorong , Bai Zhaofang , Chen Yuanyuan , Shi Wei , Yang Huijie , Li Ruisheng , Zhan Xiaoyan , Liu Youping , Zhao Xu , Xiao Xiaohe
Published: August 2024

Background

Squama Manis is a valuable traditional Chinese medicine with a long history of medicinal use in the treatment of breast-related diseases. However, owing to the excessive exploitation and utilization of the resources, Squama Manis has been included in the list of rare and endangered wild animals. The conservation of the resources of Squama Manis and continuing its clinical application has become an urgent problem, and the search for small-molecule substitutes for Squama Manis is an effective way to achieve this goal. Previous studies have identified PA3264 as a possible active ingredient in Squama Manis. In this study, we systematically investigated the pharmacological effects and mechanisms of PA3264 in the treatment of triple-negative breast cancer (TNBC), a representative breast-related disease.

Methods

Cell viability and colony formation assays were performed after treatment with the target dipeptide PA3264 in vitro. Next, 4T1 orthotopic tumors and humanized PBMC-CDX mouse models were generated to examine the antitumor effect of PA3264 in vivo. Transcriptome sequencing and molecular docking experiments were performed to predict pathways to function. Western blotting and quantitative real-time PCR were used to validate the molecular mechanisms underlying the anticancer effects of PA3264.

Results

PA3264 significantly inhibited cell viability and migration of breast cancer cells in vitro. Furthermore, PA3264 suppressed the tumor size and reduced the tumor weight in vivo. Finally, it was verified that PA3264 prevented the progression of breast cancer by inhibiting the PI3K/AKT/NF-κB pathway, causing cell cycle arrest, and promoting apoptosis.

Conclusions

This study elucidated that PA3264 derived from rare and endangered Squama Manis was a novel bioactive peptide for treating triple-negative breast cancer from a scientific research perspective.
The value of the reflective discussion in decision-making using multi-criteria decision analysis (MCDA): an example of determining the value contribution of tabelecleucel for the treatment of the Epstein Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD)
Authors: Badia Xavier , Calleja Miguel Ángel , Escudero-Vilaplana Vicente , Pérez-Martínez Antonio , Piñana José Luis , Poveda José Luis , Vallès Joan-Antoni
Published: August 2024

Background

The aim of this study was to assess the contribution of the reflective multidisciplinary discussion in determining the value contribution of innovative drugs through the multi-criteria decision analysis (MCDA). This methodology considers all relevant criteria for healthcare decision-making in a global, transparent, and systematic manner and from the perspective of relevant stakeholders. The determination of value contribution of tabelecleucel for the treatment of Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD) compared to salvage therapy was used as an example.

Results

Tabelecleucel obtained a value contribution score of 0.63 and increased to 0.75 after the reflective discussion. EBV+ PTLD was considered a life-threatening disease (5.0 ± 0.0), with a significant unmet need for an approved treatment (5.0 ± 0.0). Tabelecleucel was perceived as bringing improvements in terms of efficacy (4.2 ± 0.8) and safety (3.8 ± 0.8) compared to the salvage therapy. Most experts considered that the high efficacy and safety results could represent an improvement in the quality of life of patients (2.3 ± 1.2) along with savings in medical costs (2.3 ± 2.0) and non-medical costs (2.7 ± 1.6) compared to the salvage therapy. However, others emphasized the need of more evidence to confirm these improvements and savings over time. Tabelecleucel was regarded as potentially modifying the clinical course of the disease (4.3 ± 0.8) and supported by high-quality evidence (3.2 ± 0.4). All contextual criteria were valued highly positively for tabelecleucel. "Safety/Tolerability" and "Other medical costs" were the criteria that experienced the highest change in the re-test conducted after the reflective discussion. The reflective discussion allowed resolving doubts or misinterpretations of the experts, so the re-test obtained more accurate and consistent results of the value contribution of tabelecleucel.

Conclusions

The study shows that the MCDA methodology is a useful tool for decision-making on innovative treatments for the management of rare diseases. It also highlights the importance of reflective multidisciplinary discussion for its ability to resolve doubts or misinterpretations of experts, subsequently allowing to obtain more consistent and reliable results on the value contribution of the drug, being potentially more positive.
Protocadherin 19 regulates axon guidance in the developing Xenopus retinotectal pathway
Authors: Jung Jane , Park Jugeon , Park Sihyeon , Kim Chul Hoon , Jung Hosung
Published: August 2024

Protocadherin 19 (Pcdh19) is a homophilic cell adhesion molecule and is involved in a variety of neuronal functions. Here, we tested whether Pcdh19 has a regulatory role in axon guidance using the developing Xenopus retinotectal system. We performed targeted microinjections of a translation blocking antisense morpholino oligonucleotide to knock down the expression of Pcdh19 selectively in the central nervous system. Knocking down Pcdh19 expression resulted in navigational errors of retinal ganglion cell (RGC) axons specifically at the optic chiasm. Instead of projecting to the contralateral optic tectum, RGC axons in the Pcdh19-depleted embryo misprojected ipsilaterally. Although incorrectly delivered into the ipsilateral brain hemisphere, these axons correctly reached the optic tectum. These data suggest that Pcdh19 has a critical role in preventing mixing of RGC axons originating from the opposite eyes at the optic chiasm, highlighting the importance of cell adhesion in bundling of RGC axons.
Molecular understanding and clinical aspects of tumor-associated macrophages in the immunotherapy of renal cell carcinoma
Authors: Liu Han , Lv Zongwei , Zhang Gong , Yan Zhenhong , Bai Song , Dong Dan , Wang Kefeng
Published: August 2024

Renal cell carcinoma (RCC) is one of the most common tumors that afflicts the urinary system, accounting for 90–95% of kidney cancer cases. Although its incidence has increased over the past decades, its pathogenesis is still unclear. Tumor-associated macrophages (TAMs) are the most prominent immune cells in the tumor microenvironment (TME), comprising more than 50% of the tumor volume. By interacting with cancer cells, TAMs can be polarized into two distinct phenotypes, M1-type and M2-type TAMs. In the TME, M2-type TAMs, which are known to promote tumorigenesis, are more abundant than M1-type TAMs, which are known to suppress tumor growth. This ratio of M1 to M2 TAMs can create an immunosuppressive environment that contributes to tumor cell progression and survival. This review focused on the role of TAMs in RCC, including their polarization, impacts on tumor proliferation, angiogenesis, invasion, migration, drug resistance, and immunosuppression. In addition, we discussed the potential of targeting TAMs for clinical therapy in RCC. A deeper understanding of the molecular biology of TAMs is essential for exploring innovative therapeutic strategies for the treatment of RCC.
Association between glycemic status and all-cause mortality among individuals with dementia: a nationwide cohort study
Authors: Huh Youn , Park Kye-Yeung , Han Kyungdo , Jung Jin-Hyung , Cho Yoon Jeong , Park Hye Soon , Nam Ga Eun , Lim Soo
Published: August 2024

Background

To examine the association between glycemic status and all-cause mortality risk among individuals with dementia.

Methods

We enrolled 146,832 individuals aged 40 and older with dementia as identified through the Korean National Health Insurance Service health screening test between 2008 and 2016. Mortality status was evaluated at the end of 2019. Participants were classified into normoglycemia, prediabetes, or diabetes mellitus (DM) categories. The duration of diabetes was noted in those with DM. This study focused on the association between glycemic status and all-cause mortality.

Results

The cohort, which was predominantly elderly (average age 75.1 years; 35.5% male), had a 35.2% mortality rate over an average 3.7-year follow-up. DM was linked with increased all-cause mortality risk (hazard ratio [HR] 1.34; 95% confidence interval [CI]: 1.32–1.37) compared to non-DM counterparts. The highest mortality risk was observed in long-term DM patients (≥ 5 years) (HR 1.43; 95% CI: 1.40–1.47), followed by newly diagnosed DM (HR 1.35; 95% CI: 1.30–1.40), shorter-term DM (< 5 years) (HR 1.17; 95% CI: 1.13–1.21), and prediabetes (HR 1.03; 95% CI: 1.01–1.05). These patterns persisted across Alzheimer’s disease and vascular dementia, with more pronounced effects observed in younger patients.

Conclusions

Glucose dysregulation in dementia significantly increased mortality risk, particularly in newly diagnosed or long-standing DM. These findings suggest the potential benefits of maintaining normal glycemic levels in improving the survival of patients with dementia.
Sex-specific cardiac remodeling in aged rats after adolescent chronic stress: associations with endocrine and metabolic factors
Authors: Dearing Carley , Sanford Ella , Olmstead Nicolette , Morano Rachel , Wulsin Lawson , Myers Brent
Published: August 2024

Background

Cardiovascular disease is a leading cause of death worldwide. Rates of cardiovascular disease vary both across the lifespan and between sexes. While multiple factors, including adverse life experiences, impact the development and progression of cardiovascular disease, the potential interactions of biological sex and stress history on the aged heart are unknown. To this end, we examined sex- and stress-specific impacts on left ventricular hypertrophy (VH) after aging. We hypothesized that early-life chronic stress exposure impacts behavioral and physiologic responses that predict cardiac remodeling in a sex-specific manner.

Methods

Histological analysis was conducted on hearts of male and female rats previously exposed to chronic variable stress during the late adolescent period (postnatal days 43–62). These animals were challenged with a forced swim test and a glucose tolerance test before aging to 15 months and again being challenged. Predictive analyses were then used to isolate factors that relate to cardiac remodeling among these groups.

Results

Early-life chronic stress impacted cardiac remodeling in a sex-specific manner. Among rats with a history of chronic stress, females had increased concentric VH. However, there were few associations within the female groups among individual behavioral and physiologic parameters and cardiac remodeling. While males as a group did not have VH after chronic stress, they exhibited multiple individual associations with cardiac susceptibility. Passive coping in young males and active coping in aged males related to VH in a stress history-dependent manner. Moreover, baseline corticosterone positively correlated with VH in unstressed males, while chronically-stressed males had positive correlations between VH and visceral adiposity.

Conclusions

These results indicate that females as a group are uniquely susceptible to the effects of early-life stress on cardiac remodeling later in life. Conversely, males have more individual differences in vulnerability, where susceptibility to cardiac remodeling relates to endocrine, metabolic, and behavioral measures depending on stress history. These results ultimately support a framework for assessing cardiovascular risk based on biological sex and prior adverse experiences.
Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide
Authors: Wang Xiao-Li , Zhang Ru-Nan , Pan Yu-Lin , Li Zhi-Ming , Li Hong-Qiu , Lei Ya-Ting , Zhao Fang-Fang , Hao Xiao-Xiao , Ma Wei-Wei , Yu Cui-Ping , Yao Hong-Wei , Wang Xin-Yu , Lv Jun-Jie , Wu Yong-Hui , Wang Sheng-Yuan
Published: August 2024

Background

The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear.

Results

Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomics. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P < 0.05). Subsequent in vitro experiments using eEF2K siRNA and in vivo experiments with eEF2K-knockout mice demonstrated significant improvements in abnormal indicators related to ACR-induced learning and memory deficits (P < 0.05). Proteomic analysis of the hippocampus revealed Lpcat1 as a crucial downstream protein regulated by eEF2K. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that eEF2K may play a role in the process of ACR-induced learning and memory impairment by affecting ether lipid metabolism.

Conclusions

In summary, eEF2K as a pivotal treatment target in the mechanisms underlying ACR-induced learning and memory impairment, and studies have shown that it provides robust evidence for potential clinical interventions targeting ACR-induced impairments.
The heterogeneous effects of COVID-19 lockdowns on crime across the world
Authors: Trajtenberg N. , Fossati S. , Diaz C. , Nivette A. E. , Aguilar R. , Ahven A. , Andrade L. , Amram S. , Ariel B. , Arosemena Burbano M. J. , Astolfi R. , Baier D. , Bark H.-M. , Beijers J. E. H. , Bergman M. , Borges D. , Breetzke G. , Cano I. , Concha Eastman I. A. , Curtis-Ham S. , Davenport R. , Droppelman C. , Fleitas D. , Gerell M. , Jang K.-H. , Kääriäinen J. , Lappi-Seppälä T. , Lim W.-S. , Loureiro Revilla R. , Mazerolle L. , Mendoza C. , Meško G. , Pereda N. , Peres M. F. , Poblete-Cazenave R. , Rojido E. , Rose S. , de Ribera O. Sanchez , Svensson R. , van der Lippe T. , Veldkamp J. A. M. , Vilalta Perdomo C. J. , Zahnow R. , Eisner M. P.
Published: August 2024

There is a vast literature evaluating the empirical association between stay-at-home policies and crime during the COVID-19 pandemic. However, these academic efforts have primarily focused on the effects within specific cities or regions rather than adopting a cross-national comparative approach. Moreover, this body of literature not only generally lacks causal estimates but also has overlooked possible heterogeneities across different levels of stringency in mobility restrictions. This paper exploits the spatial and temporal variation of government responses to the pandemic in 45 cities across five continents to identify the causal impact of strict lockdown policies on the number of offenses reported to local police. We find that cities that implemented strict lockdowns experienced larger declines in some crime types (robbery, burglary, vehicle theft) but not others (assault, theft, homicide). This decline in crime rates attributed to more stringent policy responses represents only a small proportion of the effects documented in the literature.
Improved accuracy of continuum surface flux models for metal additive manufacturing melt pool simulations
Authors: Much Nils , Schreter-Fleischhacker Magdalena , Munch Peter , Kronbichler Martin , Wall Wolfgang A. , Meier Christoph
Published: August 2024

Computational modeling of the melt pool dynamics in laser-based powder bed fusion metal additive manufacturing (PBF-LB/M) promises to shed light on fundamental mechanisms of defect generation. These processes are accompanied by rapid evaporation so that the evaporation-induced recoil pressure and cooling arise as major driving forces for fluid dynamics and temperature evolution. The magnitude of these interface fluxes depends exponentially on the melt pool surface temperature, which, therefore, has to be predicted with high accuracy. The present work utilizes a diffuse interface finite element model based on a continuum surface flux (CSF) description of interface fluxes to study dimensionally reduced thermal two-phase problems representative for PBF-LB/M in a finite element framework. It is demonstrated that the extreme temperature gradients combined with the high ratios of material properties between metal and ambient gas lead to significant errors in the interface temperatures and fluxes when classical CSF approaches, along with typical interface thicknesses and discretizations, are applied. It is expected that this finding is also relevant for other types of diffuse interface PBF-LB/M melt pool models. A novel parameter-scaled CSF approach is proposed, which is constructed to yield a smoother temperature field in the diffuse interface region, significantly increasing the solution accuracy. The interface thickness required to predict the temperature field with a given level of accuracy is less restrictive by at least one order of magnitude for the proposed parameter-scaled approach compared to classical CSF, drastically reducing computational costs. Finally, we showcase the general applicability of the parameter-scaled CSF to a 3D simulation of stationary laser melting of PBF-LB/M considering the fully coupled thermo-hydrodynamic multi-phase problem, including phase change.