bluuebunny/crossref_metadata_2025 huggingface dataset:
Intralesional combined digoxin and furosemide versus intralesional 5-flurouracil for the treatment of recalcitrant plantar warts: a prospective, randomized study
Authors: khattab Fathia , Essam Reham , Elhadidy Reham F. , Anis Nourhan
Published: June 2024

There are many therapeutic modalities for plantar warts, however treating it remains challenging. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide were observed to be effective and safe, however no comparison study between them was done. Our study was conducted to evaluate the efficacy of both therapies in the treatment of plantar warts. 90 adult patients with multiple recalcitrant plantar warts were included in our study. They were randomly allocated to one of three groups; combined digoxin and furosemide, 5-fluorouarcil, or normal saline group. Fortnightly injections were done into all studied warts till complete clearance or up to 5 sessions. Warts were evaluated clinically and dermoscopically. Clinical response was reported in 24 patients (80%) of the combined digoxin and furosemide group with 40% complete response and in 24 patients (80%) of the 5-fluorouarcil group with 33.3% complete response. No statistically significant difference was observed between the two groups concerning efficacy and safety. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide are nearly equivalent in efficacy and safety for plantar wart treatment. Dermoscopy helps to take the truthful judgment about complete clearance of warts.
Effectiveness of fractional erbium–YAG laser, microneedling, platelet-rich plasma in localized stable vitiligo patients: randomized clinical trial
Authors: Abdel-Hamid Soheir , Ibrahim Hassan M. , Hameed Aya M. , Hegazy Eisa M.
Published: June 2024

Vitiligo is considered an autoimmune disease, and its treatment is challenging. We assessed and compared the effect of fractional erbium:yttrium–aluminum–garnet (Er:YAG) laser-assisted delivery of platelet-rich plasma versus microneedling (Mn) with platelet-rich plasma (PRP) in enhancing skin repigmentation in localized stable vitiligo patients. In total, 40 patients with localized stable vitiligo were selected in a random manner into two similar groups (20 each). Group (A) was subjected to fractional Er:YAG laser combined with platelet-rich plasma and Group (B) was subjected to microneedling combined with platelet-rich plasma. The procedure was repeated every 2 weeks for up to 6 months. Each individual was assessed clinically utilizing Vitiligo Area Scoring Index (VASI). Fractional Er:YAG + PRP group achieved better pigmentation100% (excellent 30%, very good 15%, good 30% and satisfactory 25%) which is comparable to Mn + PRP where 80% of cases demonstrate repigmentation (20% very good, 10% good and 50% mild). When comparing the VASI scores for both groups after therapy to the baseline VASI, there was a statistically significant decrease [p = 0.001 for group(A) and 0.003 for group(B)]. Regarding the treatment side effects, there was significantly (p = 0.048) side effects among cases treated with microneedling group(B) (25%) than those fractional Er:Yag laser therapy group(A) (5%). Both forms of therapy demonstrated induction of repigmentation of vitiligo, but fractional Er:YAG laser efficacy is greater when combined with platelet-rich plasma.

Clinical trials.gov identifier: NCT05511493.
Prevention of peritoneal adhesions after gynecological surgery: a systematic review
Authors: Schaefer Sebastian D. , Alkatout Ibrahim , Dornhoefer Nadja , Herrmann Joerg , Klapdor Ruediger , Meinhold-Heerlein Ivo , Meszaros Jozsef , Mustea Alexander , Oppelt Peter , Wallwiener Markus , Kraemer Bernhard
Published: June 2024

Importance

The formation of adhesions after gynecological surgery not only has detrimental impacts on those affected, including pain, obstruction, and infertility, but also imposes a high economic burden on healthcare systems worldwide.

Objective

The aim of this review was to evaluate the adhesion prevention potential of all currently available adhesion barriers for gynecological surgery.

Evidence acquisition

We systematically searched MEDLINE and CENTRAL databases for randomized controlled trials (RCTs) on the use of adhesion barriers as compared with peritoneal irrigation or no treatment in gynecological surgery. Only RCTs with second-look surgery to evaluate adhesions in the pelvic/abdominal (but not intrauterine) cavity were included.

Results

We included 45 RCTs with a total of 4,120 patients examining a total of 10 unique types of barriers in second-look gynecological surgery. While RCTs on oxidized regenerated cellulose (significant improvement in 6 of 14 trials), polyethylene glycol with/without other agents (4/10), hyaluronic acid and hyaluronate + carboxymethylcellulose (7/10), icodextrin (1/3), dextran (0/3), fibrin-containing agents (1/2), expanded polytetrafluoroethylene (1/1), N,O-carboxymethylchitosan (0/1), and modified starch (1/1) overall showed inconsistent findings, results for expanded polytetrafluoroethylene, hyaluronic acid, and modified starch yielded the greatest improvements regarding adhesion reduction at 75%, 0–67%, and 85%, respectively.

Conclusions and relevance

Best results for adhesion prevention were reported after applying Gore-Tex Surgical Membrane, hyaluronic acid, and 4DryField®. As Gore-Tex Surgical Membrane is nonabsorbable, it is associated with a greater risk of new adhesion formation due to second-look surgery to remove the product. 4DryField® yielded the greatest improvement in adhesion score compared to all other barrier agents (85%). For better comparability, future studies should use standardized scores and put more emphasis on patient-reported outcome measures, such as pain and infertility.
Genetics of suicide ideation. A role for inflammation and neuroplasticity?
Authors: Turiaco Fabrizio , Iannuzzo Fiammetta , Bruno Antonio , Drago Antonio
Published: June 2024

Suicide is a leading cause of death worldwide. Suicide ideation (SI) is a known risk factor for suicide behaviour (SB). The current psychobiology and genetic predisposition to SI and SB are poorly defined. Despite convincing relevance of a genetic background for SI, there is no current implementable knowledge about the genetic makeup that identifies subjects at risk for it. One of the possible reasons for the absence of a clear-cut evidence is the polygenetic nature of SI along with the very large sample sizes that are needed to observe significant genetic association result. The CATIE sample was instrumental to the analysis. SI was retrieved as measured by the Calgary test. Clinical possible covariates were identified by a nested regression model. A principal component analysis helped in defining the possible genetic stratification factors. A GWAS analysis, polygenic risk score associated with a random forest analysis and a molecular pathway analysis were undertaken to identify the genetic contribution to SI. As a result, 741 Schizophrenic individuals from the CATIE were available for the genetic analysis, including 166,325 SNPs after quality control and pruning. No GWAS significant result was found. The random forest analysis conducted by combining the polygenic risk score and several clinical variables resulted in a possibly overfitting model (OOB error rate < 1%). The molecular pathway analysis revealed several molecular pathways possibly involved in SI, of which those involved in microglia functioning were of particular interest. A medium-small sample of SKZ individuals was analyzed to shed a light on the genetic of SI. As an expected result from the underpowered sample, no GWAS positive result was retrieved, but the molecular pathway analysis indicated a possible role of microglia and neurodevelopment in SI.
A deep-learning-based model for assessment of autoimmune hepatitis from histology: AI(H)
Authors: Ercan Caner , Kordy Kattayoun , Knuuttila Anna , Zhou Xiaofei , Kumar Darshan , Koponen Ville , Mesenbrink Peter , Eppenberger-Castori Serenella , Amini Parisa , Pedrosa Marcos C. , Terracciano Luigi M.
Published: June 2024

Histological assessment of autoimmune hepatitis (AIH) is challenging. As one of the possible results of these challenges, nonclassical features such as bile-duct injury stays understudied in AIH. We aim to develop a deep learning tool (artificial intelligence for autoimmune hepatitis [AI(H)]) that analyzes the liver biopsies and provides reproducible, quantifiable, and interpretable results directly from routine pathology slides. A total of 123 pre-treatment liver biopsies, whole-slide images with confirmed AIH diagnosis from the archives of the Institute of Pathology at University Hospital Basel, were used to train several convolutional neural network models in the Aiforia artificial intelligence (AI) platform. The performance of AI models was evaluated on independent test set slides against pathologist’s manual annotations. The AI models were 99.4%, 88.0%, 83.9%, 81.7%, and 79.2% accurate (ratios of correct predictions) for tissue detection, liver microanatomy, necroinflammation features, bile duct damage detection, and portal inflammation detection, respectively, on hematoxylin and eosin-stained slides. Additionally, the immune cells model could detect and classify different immune cells (lymphocyte, plasma cell, macrophage, eosinophil, and neutrophil) with 72.4% accuracy. On Sirius red-stained slides, the test accuracies were 99.4%, 94.0%, and 87.6% for tissue detection, liver microanatomy, and fibrosis detection, respectively. Additionally, AI(H) showed bile duct injury in 81 AIH cases (68.6%). The AI models were found to be accurate and efficient in predicting various morphological components of AIH biopsies. The computational analysis of biopsy slides provides detailed spatial and density data of immune cells in AIH landscape, which is difficult by manual counting. AI(H) can aid in improving the reproducibility of AIH biopsy assessment and bring new descriptive and quantitative aspects to AIH histology.
CRISPR/Cas9-based genome-wide screening for metastasis ability identifies FCGR1A regulating the metastatic process of ovarian cancer by targeting LSP1
Authors: Qi Yingying , Zhu Weiyan , Mo Kexin , Jiang Hui
Published: June 2024

Background

Metastasis is a main cause of death from ovarian cancer (OC). Identifying key markers involved in OC metastasis can aid in the effective detection of early postoperative metastasis. However, the role of FCGR1A in OC metastasis has yet to be fully established. A genome-wide CRISPR/Cas9-based screening system was used to identify regulatory factors involved in metastasis.

Methods

The expression of FCGR1A and LSP1 in ovarian cancer cell lines was examined by quantitative real-time polymerase chain reaction (qRT‒PCR). The functions of FCGR1A and LSP1 in OC cell migration, invasion and proliferation were determined using wound healing, Transwell invasion and CKK-8 assays. A transcription-activated library was used to identify the potential downstream genes of FCGR1A. FCGR1A expression was detected by immunohistochemistry and the immunity risk score (IRS) scores were calculated.

Results

FCGR1A was upregulated in OC cells compared with normal ovarian cells. Downregulation of FCGR1A inhibited metastasis, proliferation and epithelial–mesenchymal transition (EMT) progression in OC cells in vitro and intraperitoneal metastasis in vivo. Moreover, downregulation of FCGR1A was accompanied by decreased LSP1 expression. Overexpression of LSP1 partially reversed the tumor suppressive effect of FCGR1A downregulation. Higher FCGR1A expression was related to metastasis, higher grade, higher stage, and lymph node metastasis in OC. Survival analysis suggested that the group with higher FCGR1A expression had a lower tumor-free survival rate and a lower overall survival rate than did the group with low FCGR1A expression.

Conclusions

FCGR1A enhances OC metastasis by regulating LSP1, and FCGR1A is associated with poor prognosis, suggesting that FCGR1A is a potential predictive factor for detecting early postoperative metastasis.
Pharmacological treatment of cancer pain and opioid induced nausea and vomiting: online survey and comparison with current guidelines
Authors: Gaertner Jan , Boehlke Christopher , Kreye Gudrun , Fusi-Schmidhauser Tanja , Mueller Evelyn , Roch Carmen
Published: June 2024

Purpose

We assumed that in Palliative Care, even in common clinical situations, the choice of drugs differs substantially between physicians. Therefore, we assessed the practice of pharmaceutical treatment choices of physicians for cancer pain and opioid-induced nausea and vomiting (OINV) and the rationale for their choices.

Methods

An online survey was conducted with physicians covering the following domains: i) Cancer pain therapy: non-opioids in addition to opioids: choice of drug ii) prevention of OINV: choice of drug and mode of application. Current guidelines concerning cancer pain therapy and prevention of OINV were compared.

Results

Two-hundred-forty European physicians responded to our survey. i) Use of non-opioids in addition to opioids for the treatment of cancer pain: Only 1.3% (n = 3) of respondents never used an additional non-opioid. Others mostly used: dipyrone/metamizole (49.2%, n = 118), paracetamol/acetaminophen (34.2%, n = 82), ibuprofen / other NSAIDs (11.3%, n = 27), specific Cox2-inhibitors (2.1%, n = 5), Aspirin (0.4%, n = 1), no answer (2.9%, n = 7). ii) Antiemetics to prevent OINV: The drugs of choice were metoclopramide (58.3%, n = 140), haloperidol (26.3%, n = 63), 5-HT3 antagonists (9.6%, n = 23), antihistamines (1.3%, n = 3) and other (2.9%, n = 7); no answer (1.7%, n = 4). Most respondents prescribed the substances on-demand (59.6%, n = 143) while others (36.3%, n = 87) provided them as around the clock medication. Over both domains, most physicians answered that their choices were not based on solid evidence from randomized controlled trials (RCTs). Guidelines were inconsistent regarding if and what non-opioid to use for cancer pain and recommend anti-dopaminergic drugs for prevention or treatment of OINV.

Conclusions

Physician’s practice in palliative care for the treatment of cancer pain and OINV differed substantially. Respondents expressed the lack of high-quality evidence- based information from RCTs. We call for evidence from methodologically high-quality RCTs to be available to inform physicians about the benefits and harms of pharmacological treatments for common symptoms in palliative care.
P-move: a randomized control trial of exercise in patients with advanced pancreatic or biliary tract cancer (aPBC) receiving beyond first-line chemotherapy
Authors: De Lazzari Nico , Götte Miriam , Kasper Stefan , Meier Eileen , Schuler Martin , Pogorzelski Michael , Siveke Jens T. , Tewes Mitra
Published: June 2024

Purpose

Patients with advanced pancreatic and biliary tract cancer (aPBC) frequently suffer from high symptom burden. Exercise can reduce treatment side effects and improve patient-related outcomes (PROMs). However, evidence from prospective studies regarding feasibility and efficacy in advanced settings are sparse. The primary aim of this prospective, randomized-controlled study was to evaluate the feasibility and effects of exercise (ET) in patients with aPBC.

Methods

Patients with aPBC beyond first-line therapy were randomized according to the minimization procedure with stratification by gender, age, and loss of body weight in the past six months. The intervention group (IG) completed 3 training units/week for 8 weeks (1x supervised strength sessions, 2x individualized home-based sessions). Control group (CG) received recommendations on physical activity during cancer.

Results

41 patients (stage IV pancreatic or biliary tract cancer) were included no adverse events related to exercise occurred during the trial. Physical function increased significantly in IG in 5 out of 7 physical domains. Comparison of IG and CG at 8 weeks (t2) showed significant differences in favour of IG in leg press (p=0.001), bench press (p=0.011), sit-to-stand (p=0.001) and crunch (0.006). Constipation revealed a significant difference in favour of IG at t2 (p=0.033). Quality of life stabilized/increased in IG during the study period compared to a decrease in CG. Throughout/Over the 8 weeks, fatigue notably reduced in the IG (p=0.028).

Conclusion

Exercise is safe and feasible in patients with aPBC undergoing further line therapy. Significant improvements in physical functioning and increased quality of life were achieved.

German Clinical Trials Register ID: DRKS00021179; Registration date 15.05.2020
Orthodontic maxillary molar movement-induced zygomatic pillar remodeling and its consequences on occlusal characteristics and stress distribution
Authors: Li Size , Bao Han , Su Xiaojie , Xiong Liping , Yin Qianwen , Gu Deao , Miao Leiying , Liu Chao
Published: June 2024

Objective

We aimed to evaluate changes in the zygomatic pillar during orthodontic treatment involving premolar extraction, analyze the effects of maxillary first molar movement on zygomatic pillar remodeling, and examine occlusal characteristics and stress distribution after remodeling.

Methods

Twenty-five patients who underwent premolar extraction were included in the study. The zygomatic pillar measurement range was defined, and cross-sectional areas, surface landmark coordinates, alveolar and cortical bone thicknesses, and density changes were assessed using Mimics software based on the cone-beam computed tomography scans taken before (T0) and after the treatment (T1). Multiple linear regression analysis was performed to determine the correlation between changes in the zygomatic pillar and maxillary first molar three-dimensional (3D) movement and rotation. Additionally, the correlation between pillar remodeling and occlusal characteristics was analyzed by Teetester. Pre- and post-reconstruction 3D finite element models were constructed and loaded with an average occlusal force of two periods.

Results

The morphological and structural remodeling of the zygomatic pillar after orthodontic treatment involving premolar extraction showed a decreased cross-sectional area of the lower segment of the zygomatic pillar. The zygomatic process point moved inward and backward, whereas the zygomatico-maxillary suture point moved backward. The thicknesses of the zygomatic pillar alveolar and cortical bones were thinner, and reduced alveolar bone density was observed. Simultaneously, the movement and angle change of the maxillary first molar could predict zygomatic pillar reconstruction to a certain extent. With decreasing the total occlusal force and the occlusal force of the first molar, occlusal force distribution was more uniform. With zygomatic pillar remodeling, occlusal stress distribution in the zygomatic alveolar ridge decreased, and occlusal stress was concentrated at the junction of the vertical and horizontal parts of the zygomatic bone and the posterior part of the zygomatic arch.

Conclusions

Orthodontic treatment involving premolar extraction led to zygomatic pillar remodeling, making it more fragile than before and reducing the occlusal force of the maxillary first molar and the entire dentition with stress concentrated in weak areas.

Clinical relevance

No other study has focused on the effects of orthodontics on pillar structures. The present study indicates that the mesial movement of the maxillary first molar weakened the zygomatic pillar and reduced occlusal function, thereby providing insights for inserting anchorage screws and facial esthetics.
Risk factors for PTSD symptoms following PICU admission for childhood septic shock
Authors: Corbet Burcher Georgina J. , O’Dea Lisa A. , Cooper Mehrengise K. , Lancaster Rebecca , McCutcheon Robert A. , Garralda M. Elena , Nadel Simon
Published: June 2024

Objective

Paediatric intensive care unit (PICU) admission represents a traumatic event for many children. Follow-up studies have found post-traumatic stress disorder (PTSD) rates of 10–30%, with a particular prevalence following admission for sepsis. Dysregulated inflammatory responses are associated with PTSD. Sepsis involves a marked inflammatory response but the relationship between this and PTSD have not been clearly established. In this study we investigate associations between the inflammatory response, psychosocial risk factors, and PTS symptoms following PICU admission for septic shock.

We investigate the outcomes for children aged > 3 years, discharged from one PICU following admission for septic shock between 2010 and 2017. The study was a retrospective analysis of PICU-specific PTS symptoms reported by parents at any time since discharge via the Trauma and Behavior Health screen. Demographics, pre-morbid health characteristics, and exposure to other traumatic events were assessed. Clinical characteristics and blood test results at admission and at 48 h were recorded from clinical records. Multiple linear regression was used to investigate relationships between PTS symptom scores and predictor variables.

Data for 65 participants (48% male, median assessment age 8.0 years) was available. Median time since admission was 5.1 years. 30.8% children scored at risk of PTSD at any time since discharge Symptoms were significantly associated with acute CRP rise (p 0.03), other trauma exposures (p = 0.01), and female gender (p =0.04).

PTS symptoms in children who have survived septic shock are prevalent. These findings support a possible contribution of acute inflammatory changes, cumulative traumatic exposure, and female gender in post-PICU PTSD development.
Effects of different mesh materials on complications after prophylactic placement for stoma formation: a systematic review and network meta-analysis
Authors: Meng C. , Wei Q. , Sun L. , Zhang X. , Liu Y. , Gao J. , Wei P. , Yang Z. , Yao H. , Zhang Z.
Published: June 2024

Purpose

We primary aimed to synthesise the available data, assess the effectiveness of different mesh materials in prophylactic mesh placement, and rank these materials according to the incidence of parastomal hernia (PSH) and other stoma complications.

Method

This network meta-analysis performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Four databases were searched for randomised controlled trials of prophylactic mesh placement. The aggregated results were performed in the STATA routine for Bayesian hierarchical random effects models.

Result

Thirteen randomised controlled trials from 1203 articles, met the inclusion criteria, including 681 cases without meshes, 65 cases with mesh material of xenogeneic acellular dermis (porcine/bovine), 27 cases with polypropylene/PG910, 114 cases with polypropylene/polyglecaprone (Monocryl), 117 cases with polypropylene/cellulose (ORC), 233 cases with polypropylene, and 35 cases with polypropylene/PVDF. In network A, compared with no mesh, only polypropylene (RR 0.24, 95% CI 0.04–0.80) were significantly associated with a reduction in the incidence of PSH. In network B, no statistical difference regarding stoma complications was found between mesh and no mesh.

Conclusion

Based on the network meta-analysis and ranking results, the polypropylene mesh material exhibited the best performance. However, this conclusion needs to be confirmed with larger sample sizes and high-quality randomised controlled trials.
Handwritten stenography recognition and the LION dataset
Authors: Heil Raphaela , Nauwerck Malin
Published: June 2024

In this paper, we establish the first baseline for handwritten stenography recognition, using the novel LION dataset, and investigate the impact of including selected aspects of stenographic theory into the recognition process. We make the LION dataset publicly available with the aim of encouraging future research in handwritten stenography recognition. A state-of-the-art text recognition model is trained to establish a baseline. Stenographic domain knowledge is integrated by transforming the target sequences into representations which approximate diplomatic transcriptions, wherein each symbol in the script is represented by its own character in the transliteration, as opposed to corresponding combinations of characters from the Swedish alphabet. Four such encoding schemes are evaluated and results are further improved by integrating a pre-training scheme, based on synthetic data. The baseline model achieves an average test character error rate (CER) of 29.81% and a word error rate (WER) of 55.14%. Test error rates are reduced significantly (p< 0.01) by combining stenography-specific target sequence encodings with pre-training and fine-tuning, yielding CERs in the range of 24.5–26% and WERs of 44.8–48.2%. An analysis of selected recognition errors illustrates the challenges that the stenographic writing system poses to text recognition. This work establishes the first baseline for handwritten stenography recognition. Our proposed combination of integrating stenography-specific knowledge, in conjunction with pre-training and fine-tuning on synthetic data, yields considerable improvements. Together with our precursor study on the subject, this is the first work to apply modern handwritten text recognition to stenography. The dataset and our code are publicly available via Zenodo.
Dynamic minimisation of the commute time for a one-dimensional diffusion
Authors: Hernández-Hernández Ma. Elena , Jacka Saul D.
Published: June 2024

Motivated in part by a problem in simulated tempering (a form of Markov chain Monte Carlo) we seek to minimise, in a suitable sense, the time it takes a (regular) diffusion with instantaneous reflection at 0 and 1 to travel to 1 and then return to the origin (the so-called commute time from 0 to 1). Substantially extending results in a previous paper, we consider a dynamic version of this problem where the control mechanism is related to the diffusion’s drift via the corresponding scale function. We are only able to choose the drift at each point at the time of first visiting that point and the drift is constrained on a set of the form $$[0,\ell )\cup (i,1]$$

[
0
,
ℓ
)
∪
(
i
,
1
]

. This leads to a type of stochastic control problem with infinite dimensional state.
Will senior adults accept being cognitively assessed by a conversational agent? a user-interaction pilot study
Authors: Pacheco-Lorenzo Moisés R. , Anido-Rifón Luis E. , Fernández-Iglesias Manuel J. , Valladares-Rodríguez Sonia M.
Published: June 2024

Background: early detection of dementia and Mild Cognitive Impairment (MCI) have an utmost significance nowadays, and smart conversational agents are becoming more and more capable. DigiMoCA, an Alexa-based voice application for the screening of MCI, was developed and tested. Objective: to evaluate the acceptability and usability of DigiMoCA, considering the perception of end-users and cognitive assessment administrators, through standard evaluation questionnaires. Method: a sample of 46 individuals and 24 evaluators participated in this study. End-users were fairly heterogeneous considering demographic and neuro-psychological characteristics. Evaluators were mostly health and social care professionals, relatively well-balanced in terms of gender, career background and years of experience. Results: end-users acceptability ratings were generally positive (rating above 3 in a 5-point scale for all dimensions) and it improved significantly after the interaction with DigiMoCA. Administrators also rated the usability of DigiMoCA, with an average score of 5.86/7 and with high internal consistency ($$\alpha $$
α
= 0.95). Conclusion: although there is still room for improvement in terms of user satisfaction and voice interface, DigiMoCA is perceived as an acceptable, accessible and usable cognitive screening tool, both by individuals being tested and test administrators.

Graphical abstract
The Garden of Forking Paths: Reinterpreting Haseman-Elston Regression for a Genotype-by-Environment Model
Authors: Chen Guo-Bo
Published: June 2024

Haseman-Elston regression (HE-reg) has been known as a classic tool for detecting an additive genetic variance component. However, in this study we find that HE-reg can capture GxE under certain conditions, so we derive and reinterpret the analytical solution of HE-reg. In the presence of GxE, it leads to a natural discrepancy between linkage and association results, the latter of which is not able to capture GxE if the environment is unknown. Considering linkage and association as symmetric designs, we investigate how the symmetry can and cannot hold in the absence and presence of GxE, and consequently we propose a pair of statistical tests, Symmetry Test I and Symmetry Test II, both of which can be tested using summary statistics. Test statistics, and their statistical power issues are also investigated for Symmetry Tests I and II. Increasing the number of sib pairs is important to improve statistical power for detecting GxE.
3D bioprinted mesenchymal stem cell laden scaffold enhances subcutaneous vascularization for delivery of cell therapy
Authors: Bo Tommaso , Pascucci Elia , Capuani Simone , Campa-Carranza Jocelyn Nikita , Franco Letizia , Farina Marco , Secco Jacopo , Becchi Sara , Cavazzana Rosanna , Joubert Ashley L. , Hernandez Nathanael , Chua Corrine Ying Xuan , Grattoni Alessandro
Published: June 2024

Subcutaneous delivery of cell therapy is an appealing minimally-invasive strategy for the treatment of various diseases. However, the subdermal site is poorly vascularized making it inadequate for supporting engraftment, viability, and function of exogenous cells. In this study, we developed a 3D bioprinted scaffold composed of alginate/gelatin (Alg/Gel) embedded with mesenchymal stem cells (MSCs) to enhance vascularization and tissue ingrowth in a subcutaneous microenvironment. We identified bio-ink crosslinking conditions that optimally recapitulated the mechanical properties of subcutaneous tissue. We achieved controlled degradation of the Alg/Gel scaffold synchronous with host tissue ingrowth and remodeling. Further, in a rat model, the Alg/Gel scaffold was superior to MSC-embedded Pluronic hydrogel in supporting tissue development and vascularization of a subcutaneous site. While the scaffold alone promoted vascular tissue formation, the inclusion of MSCs in the bio-ink further enhanced angiogenesis. Our findings highlight the use of simple cell-laden degradable bioprinted structures to generate a supportive microenvironment for cell delivery.

Graphical Abstract
CMR-based cardiac phenotyping in different forms of heart failure
Authors: Lange Torben , Backhaus Sören J. , Schulz Alexander , Hashemi Djawid , Evertz Ruben , Kowallick Johannes T. , Hasenfuß Gerd , Kelle Sebastian , Schuster Andreas
Published: June 2024

Heart failure (HF) is a heterogenous disease requiring precise diagnostics and knowledge of pathophysiological processes. Since structural and functional imaging data are scarce we hypothesized that cardiac magnetic resonance (CMR)-based analyses would provide accurate characterization and mechanistic insights into different HF groups comprising preserved (HFpEF), mid-range (HFmrEF) and reduced ejection fraction (HFrEF). 22 HFpEF, 17 HFmrEF and 15 HFrEF patients as well as 19 healthy volunteers were included. CMR image assessment contained left atrial (LA) and left ventricular (LV) volumetric evaluation as well as left atrioventricular coupling index (LACI). Furthermore, CMR feature-tracking included LV and LA strain in terms of reservoir (Es), conduit (Ee) and active boosterpump (Ea) function. CMR-based tissue characterization comprised T1 mapping as well as late-gadolinium enhancement (LGE) analyses. HFpEF patients showed predominant atrial impairment (Es 20.8%vs.25.4%, p = 0.02 and Ee 8.3%vs.13.5%, p = 0.001) and increased LACI compared to healthy controls (14.5%vs.23.3%, p = 0.004). Patients with HFmrEF showed LV enlargement but mostly preserved LA function with a compensatory increase in LA boosterpump (LA Ea: 15.0%, p = 0.049). In HFrEF LA and LV functional impairment was documented (Es: 14.2%, Ee: 5.4% p < 0.001 respectively; Ea: 8.8%, p = 0.02). This was paralleled by non-invasively assessed progressive fibrosis (T1 mapping and LGE; HFrEF > HFmrEF > HFpEF). CMR-imaging reveals insights into HF phenotypes with mainly atrial affection in HFpEF, ventricular affection with atrial compensation in HFmrEF and global impairment in HFrEF paralleled by progressive LV fibrosis. These data suggest a necessity for a personalized HF management based on imaging findings for future optimized patient management.
Why Do Learners (Under)Utilize Interleaving in Learning Confusable Categories? The Role of Metastrategic Knowledge and Utility Value of Distinguishing
Authors: Abel Roman , de Bruin Anique , Onan Erdem , Roelle Julian
Published: June 2024

Distinguishing easily confusable categories requires learners to detect their predictive differences. Interleaved sequences — switching between categories — help learners to detect such differences. Nonetheless, learners prefer to block — switching within a category — to detect commonalities. Across two 2 × 2-factorial experiments, we investigated why learners scarcely engage in interleaving when learning confusable categories. In Experiment 1 (N = 190), we investigated the role of the utility value of being able to distinguish confusable mushroom doubles on their spontaneous study sequence choices and of the conditional knowledge component that for distinguishing, the detection of differences (between the doubles) matters. In Experiment 2 (N = 134), we again investigated the role of the latter and additionally of the conditional knowledge component that interleaving highlights differences. Results showed that combining two factors — increasing the utility value of distinguishing and informing learners that for distinguishing, the detection of differences matters — fostered learners’ use of interleaving. In conclusion, learners are more aware that interleaving highlights differences than previously thought. Nonetheless, learners prefer blocking because they do not recognize the utility value of distinguishing, and they lack the conditional knowledge that distinguishing requires finding predictive differences. Their blocked study sequence choices reflect a deliberate investment of effort to find commonalities rather than just avoiding effort. To make learners shift their effort allocation from finding commonalities to finding differences and engage them in spontaneous interleaving, we recommend highlighting the utility value of distinguishing and informing learners about the importance of finding differences for distinguishing.
A biogas-fired cogeneration (cooling and power) system combined with biomethane facilities: 3E evaluation, sensitivity analyses and optimization
Authors: Gholizadeh Towhid , Ghiasirad Hamed , Rostami Saeed , Skorek-Osikowska Anna
Published: June 2024

The increasing demand for power and cooling generation presents a dual challenge: an unavoidable increase in carbon emissions from fossil fuel combustion and the associated difficulties in meeting the escalating investment requirements for power plant generation. As a result, there is an urgent call for the advancement of innovative cycles that not only improve performance, but also play a role in mitigating carbon emissions. This study presents a novel approach to biogas-powered cogeneration with the objective of concurrently producing electricity and cooling while utilizing heat from liquefied natural gas. The primary objective is to achieve a reduction in carbon emissions compared to similar existing work. The innovative system combines an open-loop Brayton cycle (gas turbine cycle) powered by biogas, a closed-loop Brayton cycle, a liquefied natural gas open power generation cycle, and a dual-stage combined cooling and power unit consisting of an organic Rankine cycle integrated with an ejector refrigeration cycle. A thermodynamic and economic analysis was conducted to assess the performance of the current study in comparison to previous models. To achieve optimum conditions, a comprehensive multi-objective optimization has been used, taking into account crucial decision variables, energy and exergy indicators, the carbon emission per energy ratio of the product, and the overall cost of the unit product. The results obtained underscore the environmental superiority of this system over other proposals. In the most optimal state, this system demonstrates a remarkable 48% reduction in carbon emissions. Optimization reveals that the developed unit can generate 1860 kW of net electricity and 427.3 kW of cooling. Achieving an energetic efficiency of 80.79%, an exergetic efficiency of 41.5%, a carbon emission per energy ratio of product of 9.902 kg/kW per day, and a unit cost of products of 9.816 $/GJ. In particular, the energy efficiency of the integrated gas turbine closed-loop Brayton cycle system experiences a remarkable 71.17% improvement under optimal conditions. Among the various components of the developed cogeneration system, the combustion chamber contributes the most to the overall exergy destruction rate, closely followed by the condenser, the first heat exchanger of the liquefied natural gas power system. Proposed CCP system fueled by biogas and LNG.

Graphical abstract
Nitrous oxide and methane fluxes from plasma-treated pig slurry applied to winter wheat
Authors: Lloyd I. L. , Grayson R. P. , Galdos M. V. , Morrison R. , Chapman P. J.
Published: June 2024

The use of livestock waste as an organic fertiliser releases significant greenhouse gas emissions, exacerbating climate change. Innovative fertiliser management practices, such as treating slurry with plasma induction, have the potential to reduce losses of carbon and nitrogen to the environment. The existing research on the effectiveness of plasma-treated slurry at reducing nitrous oxide (N2O) and methane (CH4) emissions, however, is not comprehensive, although must be understood if this technology is to be utilised on a large scale. A randomised block experiment was conducted to measure soil fluxes of N2O and CH4 from winter wheat every two hours over an 83-day period using automated chambers. Three treatments receiving a similar amount of plant-available N were used: (1) inorganic fertiliser (IF); (2) pig slurry combined with inorganic fertiliser (PS); (3) plasma-treated pig slurry combined with inorganic fertiliser (TPS). Cumulative N2O fluxes from TPS (1.14 g N m−2) were greater than those from PS (0.32 g N m−2) and IF (0.13 g N m−2). A diurnal pattern in N2O fluxes was observed towards the end of the experiment for all treatments, and was driven by increases in water-filled pore space and photosynthetically active radiation and decreases in air temperature. Cumulative CH4 fluxes from PS (3.2 g C m−2) were considerably greater than those from IF (− 1.4 g C m−2) and TPS (− 1.4 g C m−2). The greenhouse gas intensity of TPS (0.2 g CO2-eq kg grain−1) was over twice that of PS (0.07 g CO2-eq kg grain−1) and around six times that of IF (0.03 g CO2-eq kg grain−1). Although treating pig slurry with plasma induction considerably reduced CH4 fluxes from soil, it increased N2O emissions, resulting in higher non-CO2 emissions from this treatment. Life-cycle analysis will be required to evaluate whether the upstream manufacturing and transport emissions associated with inorganic fertiliser usage are outweighed by the emissions observed following the application of treated pig slurry to soil.
Pathways of scientific input into intergovernmental negotiations: a new agreement on marine biodiversity
Authors: Tessnow-von Wysocki Ina , Vadrot Alice B. M.
Published: June 2024

A new legally binding agreement for the conservation and sustainable use of marine biodiversity beyond national jurisdiction (BBNJ) was adopted by consensus on 19th June, 2023. Setting new regulations and filling regulatory gaps of the United Nations Convention on the Law of the Sea are expected to be informed by “best available science”. It is critical to understand how science entered the negotiations, which defined the global scientific knowledge base of decision-makers. This paper presents various pathways over which scientific input entered the BBNJ negotiations, using empirical data, collected through collaborative event ethnography, including participant observation and semi-structured interviews at the BBNJ negotiation site. Results show that scientific input in the BBNJ negotiations was not systematic and transparent but dependent on (a) available national scientific capacity, (b) financial resources, (c) established contacts and (d) active involvement of actors. Results of the study call for formalised science-policy interfaces, initiated by the UN Secretariat to guarantee a global knowledge base for decision-making. Keywords: international negotiations; United Nations; marine biodiversity; BBNJ; ocean protection; science-policy interfaces.
Exploring the Unique and Interactive Effects Between Callous-Unemotional and Autistic Traits with Parental Practices, Care, and Distress in a Community Sample
Authors: Georgiou Giorgos , Demetriou Chara A. , Fanti Kostas A.
Published: June 2024

Parental practices and stress are associated with both CU and autistic traits, with parents of children with these traits facing challenges that other parents do not encounter. However, the majority of available studies focused mainly on the unique effects of CU and autistic traits with parental stress and practices without exploring their interaction. The current study examines the distinct associations and interactions between CU and autistic traits with parental practices (parental involvement, poor monitoring, inconsistent discipline, and corporal punishment), care, and distress after considering the effect of conduct problems (CPs), age and sex in a Greek-Cypriot sample (N = 146, Mage = 7.30, SD = 1.43). Hierarchical multiple regression analysis revealed that children with CU traits were more likely to experience negative parenting, while parents showed heightened levels of distress. Notably, the study found no association between CU traits and positive parental practices. Further analysis indicated no significant relation between autistic traits and interactions with the target variables, signifying that these traits are not associated with difficulties in parenting and distress. No sex differences were found in all analyses. Age was negatively significant only in relation to parental distress These findings provide valuable insights into the impact of CU traits and underscore the need for additional studies investigating the impact of autistic traits, possibly within clinical samples.
A Brief Report on Empowering Children and Young People through Participation: Giving Space and Voice to Childhood Experiences of Domestic Violence and Abuse
Authors: Costello Áine , Holt Stephanie
Published: June 2024

Purpose

Understanding children’s experiences of living with domestic violence and abuse (DVA) is central to a child-centered, rights-based approach to working with children and young people. However, the tension between children’s right to be heard and their need to be protected from harm can often mean that those opportunities are experienced as tokenistic. In response to this concern about the reality of children’s participation in the context of DVA, the Empower Kids Project (EKP) was initiated by Barnardos [Ireland] in 2020. The EKP collaborates with partner agencies who collectively come together to provide children with a supported environment to give voice to their experiences of domestic violence and abuse. The children participate in this work within the safe and trusted relationship of their keyworker, through one to one or group work or through their support group in their local area service.

Methods

Located primarily within Lundy’s (British Educ Res J 33:927–942, 2007) model of participation, this brief report charts the journey of the EKP over the last four years across Lundy’s four quadrants of Voice, Space, Audience and Influence.

Results

Beginning with just 12 children in 2020, the EKP has to date included the voices of 74 children in its work. Analysis of the children’s journey of participation illustrates poignantly how meaningful participation is possible when scaffolded space is provided to elevate the voices of young survivors of childhood DVA. Employing child friendly multi-modal methodologies resulted in a potent sense of ownership and impact, encapsulated by one child articulating that she felt she was part of a ‘movement’.

Conclusions

The testimonies of the children and young people participating in the EKP challenge any concern that children who have experienced an adversity such as DVA may be too vulnerable to participate. Rather, the EKP participants felt part of a ‘movement’ that was influencing and creating change. Importantly, participating in the EKP has provided an otherwise marginalized and silenced group, a platform to share their experiences of living with such abuse.
Healthy, family-friendly apartment kitchen design: a study of practice in Melbourne, Australia
Authors: Kreutz A. , Sal Moslehian A. , Bower I. S. , Warner E. , Andrews F. J.
Published: June 2024

This study explored constraints and opportunities in apartment kitchen design for family home cooking and dining. An online audit of 115 two-bedroom apartments in three Melbourne suburbs of Australia was conducted, with images collected from the audit guiding photo-elicitation interviews on the kitchen designs, with architects from firms involved in apartment complex design. Affordance theory provided a conceptual lens to thematically analyse the design process and outcome in relation to architectural practice. Based on previously developed criteria, results from the audit revealed that only 18 (16%) had adequate kitchen design for families with children across five features assessed, with four themes emerging from interviews that identified constraints and facilitators to kitchen design practice: “Limited policy standards”; Architect assumptions align with market-led preferences”; “Built environment and apartment typology constraints”; and “Small scale design opportunities”. Findings provide unique insights into architects’ perspectives on apartment design, deepening understandings of how to support healthy family home food preparation and dining.
Microcalorimeter Absorber Optimization for ATHENA and LEM
Authors: Wassell Edward , Adams Joseph , Bandler Simon , Chervenak James , Cumbee Renata , Finkbeiner Fred , Fuhrman Joshua , Hull Samuel , Kelley Richard , Kilbourne Caroline , Mateo Jennette , Muramatsu Haruka , Porter Frederick , Rani Asha , Sakai Kazuhiro , Smith Stephen , Wakeham Nicholas , Yoon Sang
Published: June 2024

High quantum efficiency (QE) X-ray absorbers are needed for future X-ray astrophysics telescopes. The Advanced Telescope for High ENergy Astrophysics (ATHENA) mission requirements for the X-ray Integral Field Unit (X-IFU) instrument dictate, at their most stringent, that the absorber achieve vertical QE > 90.6% at 7 keV and low total heat capacity, 0.731 pJ/K. The absorber we have designed is 313 µm square composed of 1.05 μm Au and 5.51 μm electroplated Bi films (Barret et al. in Exp Astron 55:373–426, 2023). Overhanging the TES, the absorber is mechanically supported by 6 small legs whose 5 μm diameter is tuned to the target thermal conductance for the device. Further requirements for the absorber for X-IFU include a > 40% reflectance at wavelengths from 1 to 20 μm to reduce shot noise from infrared radiation from higher temperature stages in the cryostat. We meet this requirement by capping our absorbers with an evaporated Ti/Au thin film. Additionally, narrow gaps between absorbers are required for high fill fraction, as well as low levels of fine particulate remaining on the substrate and zero shorts between absorbers that may cause thermal crosstalk. The Light Element Mapper (LEM) is an X-ray probe concept optimized to explore the soft X-ray emission from 0.2 to 2.0 keV. These pixels for LEM require high residual resistance ratio (RRR) thin 0.5 µm Au absorbers to thermalize uniformly and narrow < 2 μm gaps between pixels for high areal fill fraction. This paper reports upon technology developments required to successfully yield arrays of pixels for both mission concepts and presents first testing results of devices with these new absorber recipes.