bluuebunny/crossref_metadata_2025_split huggingface dataset:
PARP1-targeted fluorescence molecular endoscopy as novel tool for early detection of esophageal dysplasia and adenocarcinoma
Authors: Marcazzan Sabrina , Braz Carvalho Marcos J. , Nguyen Nghia T. , Strangmann Julia , Slotta-Huspenina Julia , Tenditnaya Anna , Tschurtschenthaler Markus , Rieder Jonas , Proaño-Vasco Andrea , Ntziachristos Vasilis , Steiger Katja , Gorpas Dimitris , Quante Michael , Kossatz Susanne 
Published: February 2024

Abstract
Background
Esophageal cancer is one of the 10 most common cancers worldwide and its incidence is dramatically increasing. Despite some improvements, the current surveillance protocol with white light endoscopy and random untargeted biopsies collection (Seattle protocol) fails to diagnose dysplastic and cancerous lesions in up to 50% of patients. Therefore, new endoscopic imaging technologies in combination with tumor-specific molecular probes are needed to improve early detection. Herein, we investigated the use of the fluorescent Poly (ADP-ribose) Polymerase 1 (PARP1)-inhibitor PARPi-FL for early detection of dysplastic lesions in patient-derived organoids and transgenic mouse models, which closely mimic the transformation from non-malignant Barrett’s Esophagus (BE) to invasive esophageal adenocarcinoma (EAC).

Methods
We determined PARP1 expression via immunohistochemistry (IHC) in human biospecimens and mouse tissues. We also assessed PARPi-FL uptake in patient- and mouse-derived organoids. Following intravenous injection of 75 nmol PARPi-FL/mouse in L2-IL1B (n = 4) and L2-IL1B/IL8Tg mice (n = 12), we conducted fluorescence molecular endoscopy (FME) and/or imaged whole excised stomachs to assess PARPi-FL accumulation in dysplastic lesions. L2-IL1B/IL8Tg mice (n = 3) and wild-type (WT) mice (n = 2) without PARPi-FL injection served as controls. The imaging results were validated by confocal microscopy and IHC of excised tissues.

Results
IHC on patient and murine tissue revealed similar patterns of increasing PARP1 expression in presence of dysplasia and cancer. In human and murine organoids, PARPi-FL localized to PARP1-expressing epithelial cell nuclei after 10 min of incubation. Injection of PARPi-FL in transgenic mouse models of BE resulted in the successful detection of lesions via FME, with a mean target-to-background ratio > 2 independently from the disease stage. The localization of PARPi-FL in the lesions was confirmed by imaging of the excised stomachs and confocal microscopy. Without PARPi-FL injection, identification of lesions via FME in transgenic mice was not possible.

Conclusion
PARPi-FL imaging is a promising approach for clinically needed improved detection of dysplastic and malignant EAC lesions in patients with BE. Since PARPi-FL is currently evaluated in a phase 2 clinical trial for oral cancer detection after topical application, clinical translation for early detection of dysplasia and EAC in BE patients via FME screening appears feasible.
The impact of clinical and laboratory parameters on clinical pregnancy and live birth rates in fresh cycles: a retrospective study of 9608 high-quality cleavage-stage embryos
Authors: Zhao Haijing , Gan Keer , Ji Xiaohui , Zheng Lingyan , Ou Songbang , Mei Mei , Zhang Qingxue , Chen Hui , Yuan Ping , Wang Wenjun 
Published: February 2024

Abstract
Background
Evidence from the Istanbul consensus workshop suggests correlations between morphological parameters and embryo developments. 8-cell embryos are the best blastomere stage on day 3. No good quality evidence exists to support high-quality embryonic selection following blastulation and clinical outcomes. This study aimed to investigate the factors that affect blastocyst formation, blastocyst quality, and clinical outcomes of high-quality cleavage-stage embryos in fresh cycles.

Methods
This study was a retrospective analysis of 9608 high-quality cleavage-stage embryos from 2987 couples between January 2017 to June 2021, namely 1520 embryos categorized as “812” (8-cell, grade 2, mild fragmentation), 2961 as “821” (8-cell, grade 2, mild asymmetry), 896 as “711” (7-cell, grade 1), and 517 as “911” (9-cell, grade 1) compared with 3714 embryos categorized as “811” (8-cell, grade 1). The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR). Blastulation rate (BR), available late blastocyst rate (ABR) and high-quality late blastocyst rate (HBR) were secondary outcome measures.

Results
BR, ABR, and HBR had significant differences among the five groups (P < 0.001), while CPR and LBR were also significantly different in cleavage-stage fresh transfer (P < 0.01). The multivariable multilevel logistic regression analysis revealed a significant association between cell number, cell size, blastocyst development and clinical outcomes. For 7 to 9-cell highest-quality embryo, mild fragmentation and more blastomeres were more conducive to blastocyst formation and clinical outcomes. While cleavage-stage embryos developed into blastocysts, the negative impact of their initial morphology on clinical outcomes would be erased.

Conclusions
Our study firstly evaluated blastocyst development and clinical outcomes of high-quality cleavage-stage embryos in fresh cycles, with rankings of 811, 812, 911, 821, and 711. We found the initial morphological characteristics of the high-quality cleavage-stage embryos did not adversely impact clinical outcomes, even as they progressed to the blastocyst stage.
Application of α-bromination reaction on acetophenone derivatives in experimental teaching: a chemical innovation experiment engaging junior undergraduates
Authors: Gao Yongguang , Chen Na , Jiang Xiaoye , Yang Xiaochun 
Published: February 2024

AbstractThe α-bromination reaction of carbonyl compounds is a significant topic in the field of organic chemistry. However, due to the lack of suitable brominating reagents, the application of this reaction in undergraduate organic chemistry experiments is limited. In this study, three junior undergraduates successfully conducted an innovative experiment under the guidance of teachers. The bromination of various acetophenone derivatives was investigated by employing pyridine hydrobromide perbromide as the brominating agent, with a focus on exploring the effects of reaction time, reaction temperature, and dosage of the brominating agent. The results demonstrated that 4-chloro-α-bromo-acetophenone could be synthesized at 90 ℃ using 4-chloroacetophenone as a substrate and acetic acid as a solvent with a molar ratio of substrate to brominator being 1.0:1.1. Through the experimental teaching of 18 junior undergraduates, it was observed that all the students successfully completed the experiment within a time frame of 4–5 h, with a notable achievement yield exceeding 80% observed in 14 students. This innovative experiment exhibits significant advantages in terms of safety, high yield, cost-effectiveness, and repeatability. Furthermore, while reinforcing fundamental skills in chemistry experimentation among students, it enhances their scientific literacy levels and fosters innovation consciousness as well as practical aptitude. Consequently, this approach is highly suitable for widespread implementation and integration into undergraduate experimental pedagogy.
Development and application of a home-based exercise program for patients with cardiovascular disease: a feasibility study
Authors: Lee Mi Kyung , Lee Chan Joo , Goo Seon Young , Lee Tae Ho , Moon Jin Young , Jung Jiyoung , Kim Min Jung , Shin Sang Hee , Kim Jong Nam , Han Sung Nim , Lee Jung Eun , Lee Jong Young , Chung Ick-Mo , Jeon Justin Y. 
Published: February 2024

Abstract
Background
Cardiac rehabilitation (CR) is recommended for patients with cardiovascular disease. However, the participation and completion rates for hospital-based CR are low, and home-based CR has been suggested as an alternative. This study aimed to develop a home-based CR program and assess the feasibility of the program over a 6-week period in patients with left ventricular dysfunction or a history of myocardial infarction.

Methods
This feasibility study consisted of two phases. The initial phase (Study 1) focused on developing the home-based exercise protocol. Systematic approaches to developing evidence-based home-based exercise intervention were implemented including systematic review, patient surveys, and expert consensus. Study 2 aimed to evaluate the feasibility of a 6-week home-based CR program that was based on the results of Study 1. Study 2 included two exercise education sessions and four telephone counseling sessions. During this stage of the exercise program, the participants exercised on two separate days and their experiences while performing the aerobic and resistance exercises were surveyed. Eight participants participated in Study 1 and 16 participated in Study 2.

Results
Participants expressed overall satisfaction with the exercise program in Study 1. Heart rate increased in response to exercise, but this did not correspond with perceived exertion. The aim of the home-based CR exercise program was for participants to achieve exercise goals (≥150 min/week of aerobic type exercises as well as at least twice weekly resistance exercise using own body weights). We aimed to increase compliance and adherence to the home-based CR program. In Study 2, 13 out of 16 participants (81.3%) completed the 6-week home-based CR program, with a participation rate of 100% in both exercise education and phone counseling sessions. Adherence to the home-based exercise protocol was 83.1% and no serious adverse events were observed. At the beginning of the study, only three out of 13 participants (23.1%) met the requirements for both aerobic and resistance exercises, but at the end of the 6-week program, 10 out of 13 participants (76.9%) fulfilled the requirements.

Conclusion
The exercise program developed in this study was safe and feasible, and the 6-week home-based CR program was feasible for patients with cardiovascular disease without any reported adverse effects.
How much do Europeans know about the link between alcohol use and cancer? Results from an online survey in 14 countries
Authors: Neufeld Maria , Kokole Daša , Correia Daniela , Ferreira-Borges Carina , Olsen Aleksandra , Tran Alexander , Rehm Jürgen 
Published: February 2024

Abstract
Objective
In the EU, which has the highest drinking levels worldwide, cancer is the primary cause of alcohol-attributable deaths. Existing studies show gaps in public knowledge, but there is lack of systematic appraisal. The report presents original data from a cross-sectional survey conducted within the framework of an online experimental study in 14 European countries, which among other things assessed baseline knowledge of the alcohol-NCD link, particularly cancer.

Methods
Online questionnaire among adults who consume alcohol conducted in 14 countries in 2022–2023 using different recruitment strategies and applying population weights for the final sample. Baseline assessments measured participants’ knowledge of alcohol-attributable health issues (with a specific focus on cancer).

Results
Baseline knowledge assessment showed that 90% indicated a causal role of alcohol for liver disease, 68% for heart diseases, and only 53% for cancer. Knowledge of specific alcohol-attributable cancer types was lower, with 39% aware of the link between alcohol use and colon cancer, 28% regarding oral cancer, and only 15% regarding female breast cancer. Knowledge levels varied across different countries and population groups.

Conclusion
Most Europeans do not know which cancers can be caused by alcohol use and knowledge is low specifically for female breast cancer. More awareness raising and prevention efforts are needed, such as the placement of cancer-specific health warnings on alcohol container labels.
Reinvent 4: Modern AI–driven generative molecule design
Authors: Loeffler Hannes H. , He Jiazhen , Tibo Alessandro , Janet Jon Paul , Voronov Alexey , Mervin Lewis H. , Engkvist Ola 
Published: February 2024

AbstractREINVENT 4 is a modern open-source generative AI framework for the design of small molecules. The software utilizes recurrent neural networks and transformer architectures to drive molecule generation. These generators are seamlessly embedded within the general machine learning optimization algorithms, transfer learning, reinforcement learning and curriculum learning. REINVENT 4 enables and facilitates de novo design, R-group replacement, library design, linker design, scaffold hopping and molecule optimization. This contribution gives an overview of the software and describes its design. Algorithms and their applications are discussed in detail. REINVENT 4 is a command line tool which reads a user configuration in either TOML or JSON format. The aim of this release is to provide reference implementations for some of the most common algorithms in AI based molecule generation. An additional goal with the release is to create a framework for education and future innovation in AI based molecular design. The software is available fromhttps://github.com/MolecularAI/REINVENT4and released under the permissive Apache 2.0 license.Scientific contribution. The software provides an open–source reference implementation for generative molecular design where the software is also being used in production to support in–house drug discovery projects. The publication of the most common machine learning algorithms in one code and full documentation thereof will increase transparency of AI and foster innovation, collaboration and education.
Production of low emission briquettes from carbonized faecal sludge as an alternative source of cooking energy
Authors: Sanka Paulo Martin , Germain Olivier , Khalifa Leyla , Komakech Hans , Magambo Hezron 
Published: February 2024

Abstract
Background
In Tanzania, firewood, charcoal, and agricultural waste play a crucial role in daily life as sources of cooking energy, especially in rural areas. Using these energy sources contributes to deforestation and the emission of harmful substances, leading to health problems. This study highlights the potential of faecal sludge briquettes as an innovative, environmentally friendly, and sustainable alternative to traditional energy sources to meet the increasing demand for cooking energy in Tanzania. The process involved sludge characterization, drying, sorting, carbonization, milling, briquette making, and characterization.

Results
A study was conducted to assess the presence of zinc (Zn), cadmium (Cd), and lead (Pb) in faecal sludge collected from households. The results indicates that the levels of these metals were all within the acceptable limits set by the Tanzanian Standards (TZS) for sludge disposal and use in the environment, which are 5.00 mg/L, 5.00 mg/L, and 30.00 mg/L, respectively. Septic tanks and pit latrines sludge had a concentration of 0.5 mg/L and 0.5 mg/L for Zn, 0.55 mg/L, and 0.6 mg/L for Cd, and 10.01 mg/L and 4.87 mg/L for Pb, respectively. Adding 75% charcoal dust improved the gross and net heating values from 10.47 and 10.16 to 19.29 and 18.86 MJ/kg, respectively. Similarly, adding 50% charcoal dust improved the gross and net heating values to 19.24 and 18.78 MJ/kg. The emission of particulate matter (micrograms/m3) was reduced from 30.4 and 35 to 10.3 and 11.8 for PM2.5 and 7 and 8 for PM10, while carbon monoxide emission decreased from 51.2 to 19.7 ppm.

Conclusion
The results strongly suggest that briquettes made of carbonized faecal sludge mixed with other biomass materials could offer an alternative to traditional solid fuels, with the added benefits of reducing greenhouse gas emissions, deforestation, and longer burning times.
α-Synuclein oligomers potentiate neuroinflammatory NF-κB activity and induce Cav3.2 calcium signaling in astrocytes
Authors: Leandrou Emmanouela , Chalatsa Ioanna , Anagnostou Dimitrios , Machalia Christina , Semitekolou Maria , Filippa Vicky , Makridakis Manousos , Vlahou Antonia , Anastasiadou Ema , Vekrellis Kostas , Emmanouilidou Evangelia 
Published: February 2024

Abstract
Background
It is now realized that Parkinson’s disease (PD) pathology extends beyond the substantia nigra, affecting both central and peripheral nervous systems, and exhibits a variety of non-motor symptoms often preceding motor features. Neuroinflammation induced by activated microglia and astrocytes is thought to underlie these manifestations. α-Synuclein aggregation has been linked with sustained neuroinflammation in PD, aggravating neuronal degeneration; however, there is still a lack of critical information about the structural identity of the α-synuclein conformers that activate microglia and/or astrocytes and the molecular pathways involved.

Methods
To investigate the role of α-synuclein conformers in the development and maintenance of neuroinflammation, we used primary quiescent microglia and astrocytes, post-mortem brain tissues from PD patients and A53T α-synuclein transgenic mice that recapitulate key features of PD-related inflammatory responses in the absence of cell death, i.e., increased levels of pro-inflammatory cytokines and complement proteins. Biochemical and -omics techniques including RNAseq and secretomic analyses, combined with 3D reconstruction of individual astrocytes and live calcium imaging, were used to uncover the molecular mechanisms underlying glial responses in the presence of α-synuclein oligomers in vivo and in vitro.

Results
We found that the presence of SDS-resistant hyper-phosphorylated α-synuclein oligomers, but not monomers, was correlated with sustained inflammatory responses, such as elevated levels of endogenous antibodies and cytokines and microglial activation. Similar oligomeric α-synuclein species were found in post-mortem human brain samples of PD patients but not control individuals. Detailed analysis revealed a decrease in Iba1Low/CD68Low microglia and robust alterations in astrocyte number and morphology including process retraction. Our data indicated an activation of the p38/ATF2 signaling pathway mostly in microglia and a sustained induction of the NF-κB pathway in astrocytes of A53T mice. The sustained NF-κB activity triggered the upregulation of astrocytic T-type Cav3.2 Ca2+ channels, altering the astrocytic secretome and promoting the secretion of IGFBPL1, an IGF-1 binding protein with anti-inflammatory and neuroprotective potential.

Conclusions
Our work supports a causative link between the neuron-produced α-synuclein oligomers and sustained neuroinflammation in vivo and maps the signaling pathways that are stimulated in microglia and astrocytes. It also highlights the recruitment of astrocytic Cav3.2 channels as a potential neuroprotective mediator against the α-synuclein-induced neuroinflammation.

Graphical Abstract
Lactiplantibacillus plantarum FRT4 attenuates high-energy low-protein diet-induced fatty liver hemorrhage syndrome in laying hens through regulating gut-liver axis
Authors: Li Daojie , Cai Hongying , Liu Guohua , Han Yunsheng , Qiu Kai , Liu Weiwei , Meng Kun , Yang Peilong 
Published: February 2024

Abstract
Background
Fatty liver hemorrhage syndrome (FLHS) becomes one of the most major factors resulting in the laying hen death for caged egg production. This study aimed to investigate the therapeutic effects of Lactiplantibacillus plantarum (Lp. plantarum) FRT4 on FLHS model in laying hen with a focus on liver lipid metabolism, and gut microbiota.

Results
The FLHS model of laying hens was established by feeding a high-energy low-protein (HELP) diet, and the treatment groups were fed a HELP diet supplemented with differential proportions of Lp. plantarum FRT4. The results indicated that Lp. plantarum FRT4 increased laying rate, and reduced the liver lipid accumulation by regulating lipid metabolism (lipid synthesis and transport) and improving the gut microbiota composition. Moreover, Lp. plantarum FRT4 regulated the liver glycerophospholipid metabolism. Meanwhile, “gut-liver” axis analysis showed that there was a correlation between gut microbiota and lipid metabolites.

Conclusions
The results indicated that Lp. plantarum FRT4 improved the laying performance and alleviated FLHS in HELP diet-induced laying hens through regulating “gut-liver” axis. Our findings reveal that glycerophospholipid metabolism could be the underlying mechanism for the anti-FLHS effect of Lp. plantarum FRT4 and for future use of Lp. plantarum FRT4 as an excellent additive for the prevention and mitigation of FLHS in laying hens.
Seed tuber imprinting shapes the next-generation potato microbiome
Authors: Song Yang , Spooren Jelle , Jongekrijg Casper D. , Manders Ellen J. H. H. , de Jonge Ronnie , Pieterse Corné M. J. , Bakker Peter A. H. M. , Berendsen Roeland L. 
Published: February 2024

Abstract
Background
Potato seed tubers are colonized and inhabited by soil-borne microbes, that can affect the performance of the emerging daughter plant in the next season. In this study, we investigated the intergenerational inheritance of microbiota from seed tubers to next-season daughter plants under field condition by amplicon sequencing of bacterial and fungal microbiota associated with tubers and roots, and tracked the microbial transmission from different seed tuber compartments to sprouts.

Results
We observed that field of production and potato genotype significantly (P < 0.01) affected the composition of the seed tuber microbiome and that these differences persisted during winter storage of the seed tubers. Remarkably, when seed tubers from different production fields were planted in a single trial field, the microbiomes of daughter tubers and roots of the emerging plants could still be distinguished (P < 0.01) according to the production field of the seed tuber. Surprisingly, we found little vertical inheritance of field-unique microbes from the seed tuber to the daughter tubers and roots, constituting less than 0.2% of their respective microbial communities. However, under controlled conditions, around 98% of the sprout microbiome was found to originate from the seed tuber and had retained their field-specific patterns.

Conclusions
The field of production shapes the microbiome of seed tubers, emerging potato plants and even the microbiome of newly formed daughter tubers. Different compartments of seed tubers harbor distinct microbiomes. Both bacteria and fungi on seed tubers have the potential of being vertically transmitted to the sprouts, and the sprout subsequently promotes proliferation of a select number of microbes from the seed tuber. Recognizing the role of plant microbiomes in plant health, the initial microbiome of seed tubers specifically or planting materials in general is an overlooked trait. Elucidating the relative importance of the initial microbiome and the mechanisms by which the origin of planting materials affect microbiome assembly will pave the way for the development of microbiome-based predictive models that may predict the quality of seed tuber lots, ultimately facilitating microbiome-improved potato cultivation.