bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter, randomized, parallel-controlled clinical trial protocol to evaluate the safety and efficacy of irreversible electroporation compared with radiofrequency ablation for the treatment of small hepatocellular carcinoma
Authors: Cheng Chao , Xu Min , Pan Jinhua , Chen Qiang , Li Kai , Xu Dong , Jing Xiang , Lu Qiang , Yang Hong , Zhao Qiyu , Deng Zhuang , Jiang Tian’an 
Published: December 2024

Abstract
Background
At present, the main clinical application of local ablation therapy, such as radiofrequency ablation (RFA), is to heat the tissue to a certain temperature. However, high temperature will cause thermal damage. Irreversible electroporation (IRE) is a novel minimally invasive local ablation technology for tumors. By high-frequency pulse, the tumor cell membrane can be irretrievably perforated, resulting in the destruction of the intracellular environment, which can preserve important structures in the treatment area. However, there are no randomized controlled clinical trials comparing the efficacy of IRE with traditional local ablation in the treatment of liver cancer.

Aims
This study aims to conduct a randomized controlled clinical trial comparing the efficacy of IRE with RFA in the treatment of liver cancer.

Methods
We will conduct a multicenter, randomized, parallel-controlled non-inferiority clinical trial to compare the efficacy and safety of IRE and RFA for hepatocellular carcinoma (HCC). One hundred and ninety patients with HCC from five academic medical centers will be enrolled. The patients will be randomized into treatment arm (IRE) and control arm (RFA). The primary outcome is the progress -free survival (PFS) and the key secondary outcome is the Overall survival (OS).

Results
Forty-eight patients had been recruited from 5 centers, of which, 33 patients (median age, 59.1 years) with 38 tumors had completed the 1-month follow-up and 21 patients have complete the 3-month follow up, with 2.3 months median follow up period. The mean largest tumor diameter is 3.9 cm. No end point was observed for PFS or OS in both groups, and the complete ablation rate was 100% in both groups. The lesions in the IRE group showed obvious shrinkage 1 month after procedure. One major adverse event (AE) was occurred in the control group.

Conclusion
This is the first randomized controlled clinical trial to compare the clinical effects of IRE and RFA. The preliminary results suggest that both RFA and IRE are effective in the treatment of HCC, which can provide strong evidence for the use of IRE in HCC and provide more options for the treatment of patients with HCC.

Clinical Trial Registration
ClinicalTrials. gov, identifier NCT05451160.
Review of a specialist Rett syndrome clinic from 2003 to the COVID pandemic: clinic experience and carer perspectives
Authors: Sloper Emily , Hunt Megan , Clarke Angus John 
Published: December 2024

Abstract
Background
We have held a ‘trouble-shooting’ clinic for Rett syndrome patients from 2003 until the COVID pandemic in 2020. The clinic was multidisciplinary, including clinical genetics, paediatric neurology, adult learning disability psychiatry and physiotherapy. Access to specialist communication support and eye-gaze equipment was also often available. We have reviewed the files of patients seen in the clinic and conducted a survey of parents’ and carers’ satisfaction with the clinic and their experiences during COVID.

Results
Of the 117 patients seen in the clinic, records were reviewed of 103 (97 female, six male) who attended a total of 123 appointments. The records were unavailable for 14 patients. The most common reasons for referral were assessment of ‘episodes’ of uncertain nature (possibly epileptic, possibly autonomic), the wish for a general review by an experienced team, and questions about the diagnosis. We discuss the nature of the advice we were able to provide and offer some brief case vignettes. We wrote to the parents or carers of all patients seen and 63 respondents were willing to be interviewed about the clinic and their experiences during COVID. Respondents were generally complimentary about the clinic team, emphasising the value of a specialist clinic for those affected by a rare condition. Respondents gave insight into the range of problems experienced during COVID, especially the isolation resulting from the withdrawal of services, demonstrating the value of community support. Some respondents mentioned the shift to remote consultations, which they hoped would continue after COVID for its convenience. However, others talked about how difficult it is in a remote consultation to explain the problems of the affected family member to professionals who do not know the patient or know about Rett syndrome.

Conclusions
Our findings demonstrate the value of a disease-specific clinic provided by staff experienced with the particular rare condition. Meeting the needs of patients with ultra-rare conditions presents additional challenges. We have also found that the shift to holding a virtual clinic during COVID brought the benefit of convenience but was unsatisfactory in other ways, as it makes clinical assessment more difficult and fails to overcome the sense of isolation during a pandemic.
The impact of obesity on sleep, pulmonary and chest wall restriction in Osteogenesis Imperfecta: a pilot study
Authors: De Amicis Ramona , Landoni Vittorio , Bertoli Simona , Sartorio Alessandro , Aliverti Andrea , LoMauro Antonella 
Published: December 2024

Abstract
Introduction
Osteogenesis Imperfecta (OI) is characterised by brittle bones, severe skeletal deformities, low sleep quality, and restricted breathing. We aimed to distinguish how disease and obesity affect these results.

Methods
According to BMI, we considered four groups of peer adults (median age: 35.0 years): 13 subjects affected by moderate or severe OI without obesity (OIno), 14 affected by moderate or severe OI with obesity (OIob), 10 without obesity not affected by OI (OB) and 10 without obesity not affected by OI.

Results
Obstructive Sleep Apnoea Syndrome was diagnosed in 4 OIno (30%) and 9 OIob (64%). Restricted lung pattern (z-score of total lung capacity < − 1.64) was diagnosed in 10 OIno (77%); 9 OIob (65%), and 1 OB (10%) subjects. In the seated position, OIob breathed with reduced tidal volume and higher respiratory rate, resulting in hypoventilation. Both OIno and OIob were characterised by rapid and shallow breathing and lower ribcage expansion (negative in 3 (23%) OIno and 3 (21%) OIob). In the supine position, the ventilatory pattern was similar among the four groups, while both OIno and OIob were characterised by reduced ribcage contribution, which was negative in 6 (46%) OIno, 11 (78%) OIob and 1 (10%) OB.

Conclusions
This is a pilot study on a small sample, the findings and conclusions apply only to this study population. The preliminary results suggest that in subjects with moderate or severe OI per se implies (1) a 30% prevalence of obstructive sleep apnoea syndrome, (2) a restricted lung pattern, (3) a lower ribcage expansion, and (4) rapid and shallow breathing in the seated position. The additional impacts of obesity on OI seem to determine (1) a higher incidence of obstructive sleep apnoea syndrome, (2) hypoventilation in the seated position, and (3) a higher incidence of paradoxical breathing lying supine. Reversing obesity in OI is even more challenging as knowledge of the diet and the physical activity suited for these patients is still scarce.
Myasthenia gravis: understanding treatment patterns and direct medical costs in the Czech Republic
Authors: Donin Gleb , Mothejlová Karla , Horáková Magda , Vohanka Stanislav 
Published: December 2024

Abstract
Background
Myasthenia gravis (MG) is a rare autoimmune disorder with significant clinical implications, including life-threatening myasthenic crises and exacerbations. Understanding real-world treatment patterns, especially associated direct medical costs, is essential for the effective management of healthcare delivery.

Methods
We conducted a descriptive cohort study using health administrative claims data from the Czech Republic covering more than 1,500 prevalent MG patients. Data were analysed for healthcare resource utilization, medication costs, and hospitalization rates related to MG and its complications.

Results
Acetylcholine inhibitors and corticosteroids were widely prescribed, with 91.1% and 75.2% of patients receiving them at least once, respectively. Immunosuppressive therapy was given to 45.2% of patients. Myasthenic crises occurred in 2% of patients, with a mean hospitalization cost of 21,020 EUR, while exacerbations occurred in 9.2% of patients, with lower costs (5,951 EUR per hospitalization). Outpatient intravenous immunoglobulin and plasma exchange therapies incurred additional costs of 20,700 EUR and 18,206 EUR per person-year, respectively. The mean total cost per patient-year was 1,271 EUR, with significant cost differences among patients with different treatment patterns.

Conclusion
This study offers real-world insights into the treatment patterns and associated direct medical costs of MG in the Czech Republic. Myasthenic crises and exacerbations pose considerable cost burdens, while outpatient therapies and common pharmacotherapies are less costly. These findings are vital for healthcare planning, economic evaluation, and resource allocation, potentially leading to enhanced patient care and outcomes.
Cilengitide sensitivity is predicted by overall integrin expression in breast cancer
Authors: Girnius Nomeda , Henstridge Aylin Z. , Marks Benjamin , Yu Jeffrey K. , Gray G. Kenneth , Sander Chris , Zervantonakis Ioannis K. , Luna Augustin 
Published: December 2024

Abstract
Background
Treatment options for triple-negative breast cancer (TNBC) are limited and patients face a poor prognosis. Here, we sought to identify drugs that target TNBC vulnerabilities and understand the biology underlying these responses. We analyzed the Broad Institute DepMap to identify recurrent TNBC vulnerabilities and performed a 45-compound screen on vulnerability-related pathways on a set of up to 8 TNBC cell lines. We identified a subset of cell lines with an ITGAV vulnerability and a differential sensitivity to cilengitide, an integrin inhibitor targeting ITGAV:ITGB3 and ITGAV:ITGB5. Next, we sought to understand cilengitide resistance and response biomarkers. Clinical trials targeting integrins continue enrolling patients, necessitating an understanding of how these drugs affect tumors.

Methods
We combined in vitro assays with computational approaches to systematically explore the differential sensitivity to cilengitide and resistance mechanisms. We tested an additional pan-ITGAV inhibitor (GLPG0187) to determine how generalizable our findings on cilengitide sensitivity might be to integrin inhibition. ITGB4, ITGA3, and ITGA6 knockdown experiments assessed the importance of integrin monomers in cell attachment during cilengitide treatment. Additionally, we explored the role of extracellular matrix (ECM) proteins in cilengitide response by performing cell replating experiments and by culturing on collagen, fibronectin, or laminin coated plates.

Results
We discovered that cell-derived ECM modulates cilengitide sensitivity and exogenous fibronectin addition conferred resistance to all sensitive TNBC cell lines, though fibronectin expression did not correlate with sensitivity. Instead, elevated overall integrin protein levels, not specific integrins, in TNBC cells positively correlated with resistance. This suggested that high pan-integrin expression promotes cilengitide resistance. Thus, we tested cilengitide in six luminal breast cancer cell lines (which have low integrin levels); all were sensitive. Also, pan-ITGAV inhibitor, GLPG0187, showed the same sensitivity profile across our TNBC cell lines, suggesting our findings apply to other integrin inhibitors.

Conclusions
Integrin inhibitors are appealing candidates to pursue as anti-cancer drugs because they are generally well-tolerated, but their efficacy is mixed, possibly due to the absence of predictive markers. Cilengitide induces death in breast cancer cells with low integrin abundance, where complementary ECM promotes survival. Thus, integrin inhibition in breast cancer warrants further study.
Integrative in-silico and in-vitro analysis of taurine and vitamin B12 in modulating PPARγ and Wnt signaling in hyperhomocysteinemia-induced osteoporosis
Authors: Adhish Mazumder , Manjubala I. 
Published: December 2024

AbstractPeroxisome proliferator-activated receptor-γ (PPARγ) is a critical regulator of adipogenesis and bone metabolism, playing complex roles in osteoporosis. This study investigates the effects of taurine and homocysteine on PPARγ, focusing on their roles in osteoclastogenesis and bone health. In-silico analyses, including molecular docking and molecular dynamic simulations, revealed that both taurine and homocysteine bind competitively to the PPARγ ligand-binding domain, exhibiting distinctive antagonistic modes, including destabilization of PPARγ’s key helices H3, H4/5, H11, and H12. In-vitro experiments further supported these results, demonstrating that taurine protects against oxidative damage, enhances bone mineralization, and reduces the expression levels of PPARγ, while also downregulating negative regulators of the Wnt signaling pathway, such as SOST and DKK1. Homocysteine, on the other hand, was observed to increase the expression of these regulators and impair bone formation. Vitamin B12 was included in the study due to its known role in mitigating hyperhomocysteinemia, a condition linked to impaired bone health and reduced taurine levels. While vitamin B12 alone demonstrated some beneficial effects, it did not achieve the same level of efficacy as taurine. However, a combination of taurine and vitamin B12 showed greater efficacy in ameliorating hyperhomocysteinemia-induced osteoporosis. Overall, this study highlights taurine’s therapeutic potential in counteracting the adverse effects of hyperhomocysteinemia on bone health and underscores the need for further research into taurine’s mechanisms in osteoporosis treatment.
Graphical abstract
Leucinostatins target Plasmodium mitochondria to block malaria transmission
Authors: Niu Guodong , Wang Xiaohong , Li Jun 
Published: December 2024

Abstract
Background
Malaria remains a critical disease. Leucinostatins from the fungus Purpureocillium lilacinum inhibited the transmission of Plasmodium falciparum to mosquitoes via contact.

Methods
Here, we modified the leucinostatin B (LB) C-terminus to make derivatives and examined their inhibition against malaria transmission to mosquitoes. Fluorescence-labeled leucinostatins were incubated with intact gametocytes and were examined under microscopy to detect the targets of leucinostatins. We also analyzed leucinostatins’ general cytotoxicity and hemolysis.

Results
The results showed that the derivatives with –H, –CH3, –Atto495, and –Biotin at C-terminus had EC50 of 1.5 nM, 0.2 nM, 4.2 nM, and 42 nM, respectively. Atto495 and biotin are similar in size and much bigger than -CH3 and -H. Based on reverse-phase HPLC elution time, we found that LB-Biotin had much higher hydrophobicity than the others, consistent with its lowest malaria transmission-blocking activity. Fluorescence microscopy showed that LB-Atto495 colocalized with mitochondria inside intact P. falciparum gametocytes. We found that leucinostatin A significantly inhibited the proliferation of human nucleated cells with IC50 around 47 nM and it did not lyse erythrocytes at 100 μM.

Conclusions
We conclude that the leucinostatins pass through the cytoplasmic membrane without lysing cells and interact with molecules specifically in mitochondria. Therefore, leucinostatins should be ideal inhibitors against mobile parasites, such as ookinetes and sporozoites, during malaria transmission.

Graphical Abstract
Task-aware image quality estimators for face detection
Authors: Singh Praneet , Reibman Amy R. 
Published: December 2024

AbstractUnderstanding the quality of face images plays a critical role in enhancing the efficiency of end-to-end face analytics systems, which perform tasks such as face detection, alignment, and recognition in a sequential manner. Recently, the development of face quality estimators (QEs) specifically for face recognition has received significant attention. However, in end-to-end face analytics systems, the performance of the face detector directly affects the face recognizer. Thus, assessing the suitability of an image for face detection before passing it on to face recognition can improve the resource utilization in such systems. In this research, we first introduce the detectability (DET) score of an image, a novel quality metric that links image quality to face detection performance. We use this DET score to design two novel QEs for face detection: supervised face detection quality estimator (SFDQE) and unsupervised face detection quality estimator (UFDQE). We also propose the mAP vs. reject protocol (mvR), a systematic evaluation protocol for assessing QEs in the context of face detection. In our experiments, we illustrate the effectiveness of SFDQE and UFDQE in determining the suitability of an image for face detection. Furthermore, we show the ability of our QEs to generalize; each is a powerful tool for image quality estimation in general object detection scenarios.
Response of circulating fatty acid binding protein 4 concentration to low-intensity acute aerobic exercise is amplified in an exercise duration-dependent manner in healthy men
Authors: Numao Shigeharu , Uchida Ryota , Nakagaichi Masaki 
Published: December 2024

Abstract
Background
Circulating fatty acid-binding protein 4 (FABP4) influences cardiovascular disease and glucose metabolism. Acute aerobic exercise increases circulating FABP4 concentrations, but the factors underlying this effect in humans are unclear. We investigated the effect of exercise duration on circulating FABP4 concentrations in healthy men.

Methods
This randomized crossover study enrolled healthy young men randomly assigned to two trials, short-duration (SE) and long-duration (LE) aerobic exercises trials. Both involved acute aerobic exercise followed by 60 min of bed rest. The exercise intensity was the same (40% peak oxygen uptake); however, the duration was 40 and 70 min for the SE and LE trials, respectively. Venous blood samples were collected to measure hormones, metabolites, and FABP4 concentrations.

Results
Twelve healthy young men completed both trials. Changes in hormone levels did not differ significantly between the SE and LE trials (p > 0.05). However, the circulating FABP4 concentration increased significantly only in the LE trial immediately after exercise (p = 0.018). It increased significantly 30–60 min post-exercise in both the SE and LE trials (p < 0.018), with the extent of the increase being significantly higher in the LE trial than in the SE trial (p < 0.001). In each trial, the total incremental area under the curve of circulating FABP4 concentration was significantly positively correlated with body fat percentage (SE trial: rs = 0.699, p = 0.019; LE trial: rs = 0.643, p = 0.024).

Conclusion
Our findings suggest that exercise duration is associated with the magnitude of increased FABP4 secretion into the blood circulation. Body fat accumulation may also be involved in the magnitude of FABP4 secretion induced by acute aerobic exercise.

Trial registration
The study was pre-registered with the University Hospital Medical Information Network Center (UMIN), a clinical trial registration system (ID: UMIN000051068).
In vivo evaluation of selenium-tellurium based nanoparticles as a novel treatment for bovine mastitis
Authors: Kosaristanova Ludmila , Bytesnikova Zuzana , Fialova Tatiana , Pekarkova Jana , Svec Pavel , Ondreas Frantisek , Jemelikova Vendula , Ridoskova Andrea , Makovicky Peter , Sivak Ladislav , Dolejska Monika , Zouharova Monika , Slama Petr , Adam Vojtech , Smerkova Kristyna 
Published: December 2024

Abstract
Background
Bovine mastitis is one of the main causes of reduced production in dairy cows. The infection of the mammary gland is mainly caused by the bacterium Staphylococcus aureus, whose resistant strains make the treatment of mastitis with conventional antibiotics very difficult and result in high losses. Therefore, it is important to develop novel therapeutic agents to overcome the resistance of mastitis-causing strains. In this study, novel selenium-tellurium based nanoparticles (SeTeNPs) were synthesized and characterized. Their antibacterial activity and biocompatibility were evaluated both in vitro and in vivo using a bovine model. A total of 10 heifers were divided into experimental and control groups (5 animals each). After intramammary infection with methicillin resistant S. aureus (MRSA) and the development of clinical signs of mastitis, a dose of SeTeNPs was administered to all quarters in the experimental group.

Results
Based on in vitro tests, the concentration of 149.70 mg/L and 263.95 mg/L of Se and Te, respectively, was used for application into the mammary gland. Three days after SeTeNPs administration, MRSA counts in the experimental group showed a significant reduction (P < 0.01) compared to the control group. The inhibitory effect observed within the in vitro experiments was thus confirmed, resulting in the suppression of infection in animals. Moreover, the superior biocompatibility of SeTeNPs in the organism was demonstrated, as the nanoparticles did not significantly alter the inflammatory response or histopathology at the site of application, i.e., mammary gland, compared to the control group (P > 0.05). Additionally, the metabolic profile of the blood plasma as well as the histology of the main organs remained unaffected, indicating that the nanoparticles had no adverse effects on the organism.

Conclusions
Our findings suggest that SeTeNPs can be used as a promising treatment for bovine mastitis in the presence of resistant bacteria. However, the current study is limited by its small sample size, making it primarily a proof of the concept for the efficacy of intramammary-applied SeTeNPs. Therefore, further research with a larger sample size is needed to validate these results.