bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laminin fragments conjugated with perlecan’s growth factor-binding domain differentiate human induced pluripotent stem cells into skin-derived precursor cells
Authors: Sugiyama-Nakagiri Yoriko , Yamashita Shiho , Taniguchi Yukimasa , Shimono Chisei , Sekiguchi Kiyotoshi 
Published: September 2023

AbstractDeriving stem cells to regenerate full-thickness human skin is important for treating skin disorders without invasive surgical procedures. Our previous protocol to differentiate human induced pluripotent stem cells (iPSCs) into skin-derived precursor cells (SKPs) as a source of dermal stem cells employs mouse fibroblasts as feeder cells and is therefore unsuitable for clinical use. Herein, we report a feeder-free method for differentiating iPSCs into SKPs by customising culture substrates. We immunohistochemically screened for laminins expressed in dermal papillae (DP) and explored the conditions for inducing the differentiation of iPSCs into SKPs on recombinant laminin E8 (LM-E8) fragments with or without conjugation to domain I of perlecan (PDI), which binds to growth factors through heparan sulphate chains. Several LM-E8 fragments, including those of LM111, 121, 332, 421, 511, and 521, supported iPSC differentiation into SKPs without PDI conjugation. However, the SKP yield was significantly enhanced on PDI-conjugated LM-E8 fragments. SKPs induced on PDI-conjugated LM111-E8 fragments retained the gene expression patterns characteristic of SKPs, as well as the ability to differentiate into adipocytes, osteocytes, and Schwann cells. Thus, PDI-conjugated LM-E8 fragments are promising agents for inducing iPSC differentiation into SKPs in clinical settings.
Conversational agents enhance women's contribution in online debates
Authors: Hadfi Rafik , Okuhara Shun , Haqbeen Jawad , Sahab Sofia , Ohnuma Susumu , Ito Takayuki 
Published: September 2023

AbstractThe advent of Artificial Intelligence (AI) is fostering the development of innovative methods of communication and collaboration. Integrating AI into Information and Communication Technologies (ICTs) is now ushering in an era of social progress that has the potential to empower marginalized groups. This transformation paves the way to a digital inclusion that could qualitatively empower the online presence of women, particularly in conservative and male-dominated regions. To explore this possibility, we investigated the effect of integrating conversational agents into online debates encompassing 240 Afghans discussing the fall of Kabul in August 2021. We found that the agent leads to quantitative differences in how both genders contribute to the debate by raising issues, presenting ideas, and articulating arguments. We also found increased ideation and reduced inhibition for both genders, particularly females, when interacting exclusively with other females or the agent. The enabling character of the conversational agent reveals an apparatus that could empower women and increase their agency on online platforms.
Impact of prolonged carbapenem use-focused antimicrobial stewardship on antimicrobial consumption and factors affecting acceptance of recommendations: a quasi-experimental study
Authors: Yoo Jin Sae , Park Jeong Yong , Chun Ha-Jin , Kim Young Rong , Kim Eun Jin , Choi Young Hwa , Ha Kyoung Hwa , Heo Jung Yeon 
Published: September 2023

AbstractThis study aimed to assess the impact of a prolonged carbapenem use-focused antimicrobial stewardship program (ASP) on antimicrobial consumption and clinical outcomes and to analyze factors affecting adherence to interventions. Patients prescribed carbapenems for ≥ 2 weeks received intervention. Interrupted time-series analysis was performed to compare antimicrobial consumption before and after intervention. Factors associated with non-adherence to intervention were investigated. Of 273 patients who were eligible for intervention, discontinuation or de-escalation was recommended in 256 (94.1%) and intervention was accepted in 136 (53.1%) patients. Before intervention, carbapenem consumption significantly increased to 1.14 days of therapy (DOT)/1000 patient days (PD)/month (P = 0.018). However, it significantly declined by − 2.01 DOT/1000 PD/month without an increase in other antibiotic consumption (P < 0.001). Factors affecting non-adherence to intervention were younger age (odds ratio [OR] = 0.98; 95% confidence interval [CI] 0.96–1.00), solid organ malignancy (OR = 2.53, 95% CI 1.16–5.50), and pneumonia (OR = 2.59, 95% CI 1.08–6.17). However, ASP intervention was not associated with clinical outcomes such as length of hospital stay or mortality. Prolonged carbapenem prescription-focused ASP significantly reduced carbapenem consumption without adverse outcomes. Non-adherence to interventions was attributed more to prescriber-related factors, such as attitude, than patient-related factors including clinical severity.
Streamflow classification by employing various machine learning models for peninsular Malaysia
Authors: AlDahoul Nouar , Momo Mhd Adel , Chong K. L. , Ahmed Ali Najah , Huang Yuk Feng , Sherif Mohsen , El-Shafie Ahmed 
Published: September 2023

AbstractDue to excessive streamflow (SF), Peninsular Malaysia has historically experienced floods and droughts. Forecasting streamflow to mitigate municipal and environmental damage is therefore crucial. Streamflow prediction has been extensively demonstrated in the literature to estimate the continuous values of streamflow level. Prediction of continuous values of streamflow is not necessary in several applications and at the same time it is very challenging task because of uncertainty. A streamflow category prediction is more advantageous for addressing the uncertainty in numerical point forecasting, considering that its predictions are linked to a propensity to belong to the pre-defined classes. Here, we formulate streamflow prediction as a time series classification with discrete ranges of values, each representing a class to classify streamflow into five or ten, respectively, using machine learning approaches in various rivers in Malaysia. The findings reveal that several models, specifically LSTM, outperform others in predicting the following n-time steps of streamflow because LSTM is able to learn the mapping between streamflow time series of 2 or 3 days ahead more than support vector machine (SVM) and gradient boosting (GB). LSTM produces higher F1 score in various rivers (by 5% in Johor, 2% in Kelantan and Melaka and Selangor, 4% in Perlis) in 2 days ahead scenario. Furthermore, the ensemble stacking of the SVM and GB achieves high performance in terms of F1 score and quadratic weighted kappa. Ensemble stacking gives 3% higher F1 score in Perak river compared to SVM and gradient boosting.
The effective deficiency of biochemical networks
Authors: Langary Damoun , Küken Anika , Nikoloski Zoran 
Published: September 2023

AbstractThe deficiency of a (bio)chemical reaction network can be conceptually interpreted as a measure of its ability to support exotic dynamical behavior and/or multistationarity. The classical definition of deficiency relates to the capacity of a network to permit variations of the complex formation rate vector at steady state, irrespective of the network kinetics. However, the deficiency is by definition completely insensitive to the fine details of the directionality of reactions as well as bounds on reaction fluxes. While the classical definition of deficiency can be readily applied in the analysis of unconstrained, weakly reversible networks, it only provides an upper bound in the cases where relevant constraints on reaction fluxes are imposed. Here we propose the concept of effective deficiency, which provides a more accurate assessment of the network’s capacity to permit steady state variations at the complex level for constrained networks of any reversibility patterns. The effective deficiency relies on the concept of nonstoichiometric balanced complexes, which we have already shown to be present in real-world biochemical networks operating under flux constraints. Our results demonstrate that the effective deficiency of real-world biochemical networks is smaller than the classical deficiency, indicating the effects of reaction directionality and flux bounds on the variation of the complex formation rate vector at steady state.
A nationwide study on the current treatment status and natural prognosis of hepatocellular carcinoma in elderly
Authors: Yoo Jeong-Ju , Lee Jayoun , Choi Gi Hong , Lee Min Woo , Park Dong Ah 
Published: September 2023

AbstractThe aim of this study was to identify the treatment status and natural prognosis of hepatocellular carcinoma (HCC) patients aged 65 years or older in Korea. We analyzed 3,492 patients’ data from the liver cancer stage of the Central Cancer Registry of National Cancer Center. The most common etiology of HCC was hepatitis B (32.7%), followed by hepatitis C. 2624 patients (69.2%) received first-line active treatment for HCC. The most frequently selected treatment was transarterial chemoembolization (TACE), followed by surgical resection and radiofrequency ablation (RFA). The proportion of patients receiving supportive care increased with age. Second-line treatment was performed in only 36.7% of cases, with all others choosing supportive care. Among the various treatments, liver transplantation was found to have the greatest effect in reducing the risk of death (HR [hazard ratio] 0.164, 95% CI [confidence interval] 0.061–0.444), followed by resection, RFA, radioembolization, and TACE. A similar pattern was observed when sub-analyzing the age group over 75 years old. The median survival for untreated HCC in Barcelona Clinic Liver Cancer stage 0/A/B/C/D was 3.7 years, 2.3 years, 7.9 months, 3.9 months, and 2.9 months, respectively. This study highlights the current status of elderly patients with HCC in Korea. While the proportion of patients receiving supportive care is high among the elderly, effective treatment can improve their survival rate.
Randomized clinical trial on the effects of a computerized cognitive training for pediatric patients with acquired brain injury or congenital malformation
Authors: Corti Claudia , Oldrati Viola , Papini Marta , Strazzer Sandra , Poggi Geraldina , Romaniello Romina , Borgatti Renato , Urgesi Cosimo , Bardoni Alessandra 
Published: September 2023

AbstractBoth acquired injuries and congenital malformations often cause lifelong disabilities in children, with a significant impact on cognitive abilities. Remote computerized cognitive training (CCT) may be delivered in ecological settings to favour rehabilitation continuity. This randomized clinical trial (RCT) evaluated the efficacy of an 8-week multi-domain, home-based CCT in a sample of patients aged 11–16 years with non-progressive acquired brain injury (ABI), brain tumor (BT) and congenital brain malformation (CBM). Following a stepped-wedge research design, patients were randomized into two groups: Training-first group, which started the CCT immediately after baseline assessment and Waiting-first group, which started the CCT after a period of time comparable to that required by the training (8 weeks). Post-training and long-term (6 months) changes were assessed. Both groups improved on visual–spatial working memory after the CCT, with benefits maintained after 6 months, while no other changes in cognitive or psychological measures were found. These findings suggest that a multi-domain CCT can generate benefits in visual–spatial working memory, in accordance with data from extant literature reporting that computer games heavily engage visuo-spatial abilities. We speculate that is tapping on the same cognitive ability with a prolonged training that may generate the greatest change after a CCT.
The association between the number of oocytes retrieved and cumulative live birth rate in different female age strata
Authors: Wang Peixin , Zhao Chenqiong , Xu Wen , Jin Xiaoying , Zhang Songying , Zhu Haiyan 
Published: September 2023

AbstractTo evaluate the association between the number of oocytes retrieved and cumulative live birth rate (CLBR) in different female age strata. 17,931 women undergoing their first IVF/ICSI-ET cycle in the Sir Run Run Shaw Hospital of Zhejiang University were grouped by age (A: ≤ 35 years; B: ≥ 36 years) as well as the number of oocytes retrieved (a: ≤ 5; b:6–9; c:10–14; d: ≥ 15). Multivariate regression analysis was performed to assess the OR of CLBR for the variable ‘age’ and ‘number of oocytes retrieved’. The group ≥ 36 years exhibited lower cumulative pregnancy rates (CPRs) and cumulative live birth rates (CLBRs), which are proportional to the number of oocytes retrieved but opposite to increasing age. Multivariate logistic regression analysis revealed that the age and number of oocytes retrieved remain significant independent predictive factors (P < 0.001). Age and number of oocytes retrieved are two independent factors affecting the CLBR. The discrepancy of the minimum number of oocytes retrieved for patients with different ages to achieve ideal CLBR is instructive for clinical practice. The practice of controlling the stimulation dose is feasible for patients ≤ 35 years who can achieve over 60% CLBR once the number of oocytes obtained is more than 6. However, additional stimulation cycles and accumulation of embryos are necessary for elderly group especially those ≥ 38 years old who need more than 14 oocytes to obtain higher live birth rate.
SELEX based aptamers with diagnostic and entry inhibitor therapeutic potential for SARS-CoV-2
Authors: Halder Sayanti , Thakur Abhishek , Keshry Supriya Suman , Jana Pradip , Karothia Divyanshi , Das Jana Indrani , Acevedo Orlando , Swain Rajeeb K. , Mondal Arindam , Chattopadhyay Soma , Jayaprakash Venkatesan , Dev Abhimanyu 
Published: September 2023

AbstractFrequent mutation and variable immunological protection against vaccination is a common feature for COVID-19 pandemic. Early detection and confinement remain key to controlling further spread of infection. In response, we have developed an aptamer-based system that possesses both diagnostic and therapeutic potential towards the virus. A random aptamer library (~ 1017 molecules) was screened using systematic evolution of ligands by exponential enrichment (SELEX) and aptamer R was identified as a potent binder for the SARS-CoV-2 spike receptor binding domain (RBD) using in vitro binding assay. Using a pseudotyped viral entry assay we have shown that aptamer R specifically inhibited the entry of a SARS-CoV-2 pseudotyped virus in HEK293T-ACE2 cells but did not inhibit the entry of a Vesicular Stomatitis Virus (VSV) glycoprotein (G) pseudotyped virus, hence establishing its specificity towards SARS-CoV-2 spike protein. The antiviral potential of aptamers R and J (same central sequence as R but lacking flanked primer regions) was tested and showed 95.4% and 82.5% inhibition, respectively, against the SARS-CoV-2 virus. Finally, intermolecular interactions between the aptamers and the RBD domain were analyzed using in silico docking and molecular dynamics simulations that provided additional insight into the binding and inhibitory action of aptamers R and J.
It’s about time: small mammal communities and Lyme disease emergence
Authors: Millien V. , Leo S. S. T. , Turney S. , Gonzalez A. 
Published: September 2023

AbstractTheory predicts that biodiversity changes due to climate warming can mediate the rate of disease emergence. The mechanisms linking biodiversity-disease relationships have been described both theoretically and empirically but remain poorly understood. We investigated the relations between host diversity and abundance and Lyme disease risk in southern Quebec, a region where Lyme disease is rapidly emerging. We found that both the abundance of small mammal hosts and the relative abundance of the tick’s natural host, the white-footed mouse (Peromyscus leucopus), influenced measures of disease risk in tick vectors (Borrelia burgdorferi infection abundance and prevalence in tick vectors). Our results suggest that the increase in Lyme disease risk is modulated by regional processes involving the abundance and composition of small mammal assemblages. However, the nature and strength of these relationships was dependent both on time and geographic area. The strong effect of P. leucopus abundance on disease risk we report here is of significant concern, as this competent host is predicted to increase in abundance and occurrence in the region, with the northern shift in the range of North American species under climate warming.
The canonical E2Fs together with RETINOBLASTOMA-RELATED are required to establish quiescence during plant development
Authors: Gombos Magdolna , Raynaud Cécile , Nomoto Yuji , Molnár Eszter , Brik-Chaouche Rim , Takatsuka Hirotomo , Zaki Ahmad , Bernula Dóra , Latrasse David , Mineta Keito , Nagy Fruzsina , He Xiaoning , Iwakawa Hidekazu , Őszi Erika , An Jing , Suzuki Takamasa , Papdi Csaba , Bergis Clara , Benhamed Moussa , Bögre László , Ito Masaki , Magyar Zoltán 
Published: September 2023

AbstractMaintaining stable and transient quiescence in differentiated and stem cells, respectively, requires repression of the cell cycle. The plant RETINOBLASTOMA-RELATED (RBR) has been implicated in stem cell maintenance, presumably by forming repressor complexes with E2F transcription factors. Surprisingly we find that mutations in all three canonical E2Fs do not hinder the cell cycle, but similarly to RBR silencing, result in hyperplasia. Contrary to the growth arrest that occurs when exit from proliferation to differentiation is inhibited upon RBR silencing, the e2fabc mutant develops enlarged organs with supernumerary stem and differentiated cells as quiescence is compromised. While E2F, RBR and the M-phase regulatory MYB3Rs are part of the DREAM repressor complexes, and recruited to overlapping groups of targets, they regulate distinct sets of genes. Only the loss of E2Fs but not the MYB3Rs interferes with quiescence, which might be due to the ability of E2Fs to control both G1-S and some key G2-M targets. We conclude that collectively the three canonical E2Fs in complex with RBR have central roles in establishing cellular quiescence during organ development, leading to enhanced plant growth.
Multi-omics data provide insight into the adaptation of the glasshouse plant Rheum nobile to the alpine subnival zone
Authors: Li Ying , Niu Zhimin , Zhu Mingjia , Wang Zhenyue , Xu Renping , Li Minjie , Zheng Zeyu , Lu Zhiqiang , Dong Congcong , Hu Hongyin , Yang Yingbo , Wu Ying , Wang Dandan , Yang Jinli , Zhang Jin , Wan Dongshi , Abbott Richard , Liu Jianquan , Yang Yongzhi 
Published: September 2023

AbstractSubnival glasshouse plants provide a text-book example of high-altitude adaptation with reproductive organs enclosed in specialized semi-translucent bracts, monocarpic reproduction and continuous survival under stress. Here, we present genomic, transcriptomic and metabolomic analyses for one such plant, the Noble rhubarb (Rheum nobile). Comparative genomic analyses show that an expanded number of genes and retained genes from two recent whole-genome duplication events are both relevant to subnival adaptation of this species. Most photosynthesis genes are downregulated within bracts compared to within leaves, and indeed bracts exhibit a sharp reduction in photosynthetic pigments, indicating that the bracts no longer perform photosynthesis. Contrastingly, genes related to flavonol synthesis are upregulated, providing enhanced defense against UV irradiation damage. Additionally, anatomically abnormal mesophyll combined with the downregulation of genes related to mesophyll differentiation in bracts illustrates the innovation and specification of the glass-like bracts. We further detect substantial accumulation of antifreeze proteins (e.g. AFPs, LEAs) and various metabolites (e.g. Proline, Protective sugars, procyanidins) in over-wintering roots. These findings provide new insights into subnival adaptation and the evolution of glasshouse alpine plants.
Size-dependent charging of dust particles in protoplanetary disks
Authors: Balduin T. , Woitke P. , Jørgensen U. G. , Thi W.-F. , Narita Y. 
Published: September 2023

Context.Lightning can have a profound impact on the chemistry of planetary atmospheres. In a similar manner, as protoplanetary disks are the foundation of planet formation, the emergence of lightning in protoplanetary disks can substantially alter their chemistry.Aims.We aim to study under which conditions lightning could emerge within protoplanetary disks.Methods.We employed the PRODIMOcode to make 2D thermo-chemical models of protoplanetary disks. We included a new way of how the code handles dust grains, which allows the consideration of dust grains of different sizes. We investigated the chemical composition, dust charging behavior, and charge balance of these models to determine which regions could be most sufficient for lightning.Results.We identify six regions within the disks where the charge balance is dominated by different radiation processes and find that the emergence of lightning is most probable in the lower and warmer regions of the midplane. This is due to the low electron abundance (nе/n〈H〉< 10−15) in these regions and dust grains being the most abundant negative charge carriers (nZ/n〈H〉> 10−13). We find that NH4+is the most abundant positive charge carrier in those regions at the same abundances as the dust grains. We developed a method of inducing electric fields via turbulence within this mix of dust grains and NH4+. The electric fields generated with this mechanism are however several orders of magnitude weaker than required to overcome the critical electric field.
Der Teufelskreis zwischen Arbeitslosigkeit und Substanzgebrauchsstörungen
Authors: Nolte-Troha Carina , Neumann Stefanie , Franke Andreas G. 
Published: September 2023

ZUSAMMENFASSUNG
Hintergrund Die Beziehung zwischen Arbeitslosigkeit und Erkrankungen findet in der Wissenschaft zwar Beachtung, der Zusammenhang zwischen Arbeitslosigkeit und Substanzgebrauchsstörungen aber weit weniger.
Methoden Eine systematische Literaturanalyse zu den Begriffen „unemployment”, „substance use”, „drugs”, „alcohol”, „nicotine” und „tobacco” wurde durchgeführt.
Ergebnisse Es gibt einen signifikanten Zusammenhang zwischen Arbeitslosigkeit und Substanzgebrauchsstörungen, wobei unstrittig ist, dass Substanzgebrauchsstörungen die Wahrscheinlichkeit von Arbeitslosigkeit signifikant erhöhen. Die Wahrscheinlichkeit, dass aber Arbeitslosigkeit wiederum zu Substanzgebrauchsstörungen führt, ist in der Studienlage multifaktoriell und weniger klar. Studien zur Beziehung zwischen Arbeitslosigkeit und Konsumrückfallgefahr sowie Arbeitslosigkeit und dem Beenden des Substanzkonsums sind zudem uneindeutig. Auch lässt sich die Frage nach dem Zusammenhang zwischen Wirtschaftszyklen und Substanzkonsumstörungen nicht eindeutig beantworten.
Konklusion Arbeitslosigkeit und Substanzgebrauchsstörungen sind mehr oder weniger deutlich miteinander assoziiert. Beide führen meist zu (weiteren) körperlichen und psychischen Störungen sowie insbesondere zu psychosozialen Schwierigkeiten und einer Prekarisierung von Lebensumständen.
Klinische Relevanz Es gilt ärztlicherseits Substanzgebrauchsstörungen frühzeitig zu erkennen und auf ein Sistieren des Substanzkonsums hinzuwirken, um negative Konsequenzen und insbesondere Arbeitslosigkeit zu verhindern.