bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning models for predicting of PD-1 treatment efficacy in Pan-cancer patients based on routine hematologic and biochemical parameters
Authors: Yang Wenjian , Chen Cui , Ouyang Qiangqiang , Han Runkun , Sun Peng , Chen Hao 
Published: July 2024

AbstractImmune checkpoint blockade therapy targeting the programmed death-1(PD-1) pathway has shown remarkable efficacy and durable response in patients with various cancer types. Early prediction of therapeutic efficacy is important for optimizing treatment plans and avoiding potential side effects. In this work, we developed an efficient machine learning prediction method using routine hematologic and biochemical parameters to predict the efficacy of PD-1 combination treatment in Pan-Cancer patients. A total of 431 patients with nasopharyngeal carcinoma, esophageal cancer and lung cancer who underwent PD-1 checkpoint inhibitor combination therapy were included in this study. Patients were divided into two groups: progressive disease (PD) and disease control (DC) groups. Hematologic and biochemical parameters were collected before and at the third week of PD-1 therapy. Six machine learning models were developed and trained to predict the efficacy of PD-1 combination therapy at 8–12 weeks. Analysis of 57 blood biomarkers before and after three weeks of PD-1 combination therapy through statistical analysis, heatmaps, and principal component analysis did not accurately predict treatment outcome. However, with machine learning models, both the AdaBoost classifier and GBDT demonstrated high levels of prediction efficiency, with clinically acceptable AUC values exceeding 0.7. The AdaBoost classifier exhibited the highest performance among the 6 machine learning models, with a sensitivity of 0.85 and a specificity of 0.79. Our study demonstrated the potential of machine learning to predict the efficacy of PD-1 combination therapy based on changes in hematologic and biochemical parameters.
Circular RNA circ_ARHGEF28 inhibits MST1/2 dimerization to suppress Hippo pathway to induce cisplatin resistance in ovarian cancer
Authors: Lei Ruilin , Long Yun , Li Qingjian , Xie Qingsheng , Ling Xiaoting , Xie Meiqing , Zhou Hui , Zhang Bingzhong 
Published: July 2024

Abstract
Background
Cisplatin is integral to ovarian cancer treatment, yet resistance to this drug often results in adverse patient outcomes. The association of circular RNA (circRNA) with cisplatin resistance in ovarian cancer has been observed, but the mechanisms governing this relationship require further elucidation.

Methods
High-throughput sequencing was utilized to profile circRNA expression in cisplatin-resistant ovarian cancer cells. Gain-and-loss-of-function experiments assessed the impact on cisplatin sensitivity, both in vitro and in vivo. Fluorescence in situ hybridization was conducted to determine the cellular distribution of circRNAs, and RNA pulldown and immunoprecipitation experiments were performed to identify associated binding proteins.

Results
The study revealed that circ_ARHGEF28 is overexpressed in certain cisplatin-resistant ovarian cancer tissues and cell lines, and is associated with reduced progression-free survival in patients. It was observed that circ_ARHGEF28 contributes to cisplatin resistance in ovarian cancer models, both in vitro and in vivo. Importantly, circ_ARHGEF28 was found to interact directly with MST1/2, inhibiting the SARAH coiled-coil binding domains and consequently deactivating the Hippo pathway.

Conclusion
This investigation identifies circ_ARHGEF28 as a novel circRNA that contributes to cisplatin resistance in ovarian cancer by suppressing the Hippo pathway. Therapeutic strategies targeting circ_ARHGEF28 may offer a potential avenue to mitigate cisplatin resistance in ovarian cancer treatment.
Evidence on sulfadoxine-pyrimethamine resistance molecular markers from India: interpret with caution
Authors: Deora Nimita , Sinha Abhinav 
Published: July 2024

Abstract
Background
Sulfadoxine-pyrimethamine (SP), as a partner to artesunate as ACT is the treatment of choice for uncomplicated P. falciparum infections in the majority of India and SP-resistance has a potential to lead to ACT failure. In the lack of robust surveillance of therapeutic efficacy of SP, validate molecular markers of SP-resistance offer a hint of failing SP. However, studies reporting these validated markers often suffer from certain pitfalls that warrant a careful interpretation.

Main body
Critical analyses of the results and their reported interpretations from a recent study and other studies conducted on the WHO-validated molecular markers of SP-resistance in India were analysed and the main problems with studying and reporting of these markers are presented here. It was noted that almost all studies analysed flawed either on the usage, estimation and/or interpretation of the standardized classification of the studies SP mutations. These flaws not only impart spatiotemporal incomparability of the published data but also have the potential of being misunderstood and wrongly translated.

Conclusion
Based on this universal problem in studying, reporting and interpreting the data from the studies on molecular markers of SP-resistance, it is stressed that the future studies should be conducted with utmost caution so that robust evidence may be generated and correctly translated to policy.
Validation of a digital food frequency questionnaire for the Northern Sweden Diet Database
Authors: Wennberg Maria , Kastenbom Lisa , Eriksson Linda , Winkvist Anna , Johansson Ingegerd 
Published: July 2024

Abstract
Background
Dietary habits strongly influence health, with poor diets contributing to numerous deaths annually. Addressing this requires improved dietary habits and consistent monitoring thereof. In northern Sweden, a validated food frequency questionnaire (FFQ) has been used for decades, but trends show that its ability to accurately measure intake has diminished. With changing eating habits and food supply, updating the FFQ was crucial, leading to the development of FFQ2020. This study assessed FFQ2020’s relative validity using 24-hour recalls and evaluated its reproducibility.

Methods
Participants were recruited from one of the northern-Sweden population-based health screenings and by advertising. Food intake was registered in an electronic food frequency questionnaire (FFQ2020) (test instrument) and reference data were obtained by six repeated electronic 24-hour dietary recalls (24HDR). Intakes of single foods were aggregated into food groups and healthy diet index scores, and daily energy and nutrient intakes were estimated. Results from the two methods were described and tested in univariate analyses and correlation tests, Bland Altman plots, cross-classification validity, and intra-class correlation analyses.

Results
Totally, 628 adults were invited to participate in the study. Of these, 320 joined, and 244 completed at least four 24HDRs. The median intakes in food groups, as well as the mean index scores and estimated nutrient intakes, were largely similar between the FFQ2020 and 24HDR recordings. The correlation coefficients between the two assessments ranged from 0.253 to 0.693 for food groups, 0.520 to 0.614 for diet indices, and 0.340 to 0.629 for energy and nutrients. Intra-class correlation coefficients indicated at least good reproducibility for intakes of food groups, diet index scores, and nutrients. Generally, Bland-Altman plots did not reveal any gross systematic disagreement between the two methods for any of the assessments. However, there were single observations located outside the upper or lower 95% confidence interval (CI) limits for the difference between FFQ2020 and the 24HDR recordings.

Conclusion
In concert, the results suggest that the relative validity and reproducibility of FFQ2020 are acceptable for trend analyses and group comparisons in large-scale studies but also that extended reference periods would improve the precision of less frequently consumed foods.
PEDF-34 attenuates neurological deficit and suppresses astrocyte-dependent neuroinflammation by modulating astrocyte polarization via 67LR/JNK/STAT1 signaling pathway after subarachnoid hemorrhage in rats
Authors: Wu Lei , Liu Yanchao , He Qiuguang , Ao Guangnan , Xu Ningbo , He Wangqing , Liu Xiao , Huang Lei , Yu Qian , Kanamaru Hideki , Dong Siyuan , Zhu Shiyi , Yuan Ye , Han Mingyang , Ling Yeping , Liu Lu , Wu Chenyu , Zhou You , Sherchan Prativa , Flores Jerry J. , Tang Jiping , Chen Xionghui , He Xuying , Zhang John H. 
Published: July 2024

Abstract
Background
Reactive astrocytes participate in various pathophysiology after subarachnoid hemorrhage (SAH), including neuroinflammation, glymphatic–lymphatic system dysfunction, brain edema, BBB disruption, and cell death. Astrocytes transform into two new reactive phenotypes with changed morphology, altered gene expression, and secretion profiles, termed detrimental A1 and beneficial A2. This study investigates the effect of 67LR activation by PEDF-34, a PEDF peptide, on neuroinflammation and astrocyte polarization after the experimental SAH.

Methods
A total of 318 male adult Sprague-Dawley rats were used in experiments in vivo, of which 272 rats were subjected to the endovascular perforation model of SAH and 46 rats underwent sham surgery. 67LR agonist (PEDF-34) was administrated intranasally 1 h after SAH. 67LR-specific inhibitor (NSC-47924) and STAT1 transcriptional activator (2-NP) were injected intracerebroventricularly 48 h before SAH. Short- and long-term neurological tests, brain water content, immunostaining, Nissl staining, western blot, and ELISA assay were performed. In experiments in vitro, primary astrocyte culture with hemoglobin (Hb) stimulation was used to mimic SAH. The expression of the PEDF-34/67LR signaling pathway and neuro-inflammatory cytokines were assessed using Western blot, ELISA, and immunohistochemistry assays both in vivo and in vitro.

Results
Endogenous PEDF and 67LR expressions were significantly reduced at 6 h after SAH. 67LR was expressed in astrocytes and neurons. Intranasal administration of PEDF-34 significantly reduced brain water content, pro-inflammatory cytokines, and short-term and long-term neurological deficits after SAH. The ratio of p-JNK/JNK and p-STAT1/STAT1 and the expression of CFB and C3 (A1 astrocytes marker), significantly decreased after PEDF-34 treatment, along with fewer expression of TNF-α and IL-1β at 24 h after SAH. However, 2-NP (STAT1 transcriptional activator) and NSC-47924 (67LR inhibitor) reversed the protective effects of PEDF-34 in vivo and in vitro by promoting A1 astrocyte polarization with increased inflammatory cytokines.

Conclusion
PEDF-34 activated 67LR, attenuating neuroinflammation and inhibiting astrocyte A1 polarization partly via the JNK/STAT1 pathway, suggesting that PEDF-34 might be a potential treatment for SAH patients.

Graphical Abstract
Verification of Protection Performance of Concrete Blast-Proof Panels Against Internal Explosions
Authors: Park Sangwoo , Kim Kukjoo , Kim Dongku , Park Young-Jun , Shim Byul 
Published: July 2024

AbstractRecently, studies on blast-proof panels, which were attached to structures to protect facilities from local damage caused by explosions, have been actively performed. However, blast-proof panels are impractical yet due to the high installation cost and difficulty in construction, and protection performance for explosions inside a structure is not evaluated. In this study, a blast-proof panel consisting of concrete material was devised to ensure economic feasibility and constructability. Then, the protection performance of the concrete blast-proof panel for internal explosions was analyzed by numerical simulations and field experiments. First, field experiments on concrete explosion-proof panels were conducted for two cases, where panels without and with energy-absorbing foam were installed. As a result, the concrete blast-proof panel reduced the displacement of structures by up to 22% and the acceleration of structures by up to 86%. However, the reliability of the field experiment data was insufficient due to the shear failure of the test structure during experiments. Therefore, additional analysis was conducted by developing a numerical model. A series of numerical simulations was conducted according to the various densities of the energy-absorbing foam that was inserted between the panel and structure. Consequently, the optimum density of the impact-absorbing material differed depending on the type of structure damage to reduce (i.e., the displacement or acceleration of the structure).
Recycling potato waste for the production of blue pigments by Streptomyces lydicus PM7 through submerged fermentation
Authors: Astudillo Álvaro , Hormazábal Emilio , Quiroz Andrés , Rubilar Olga , Briceño Gabriela , Abdala Roberto , Lamilla Claudio , Diez María Cristina , Schalchli Heidi 
Published: July 2024

Abstract
Background
Discarded potato is the most abundant potato waste and represents a worldwide disposal problem to the potato industry. This agricultural waste contains valuable nutrients that could be used as substrate to obtain diverse high value-added microbial products, such as biopigments. The aim of this work was to evaluate the use of discarded potato as a sole substrate source for producing blue pigments by Streptomyces lydicus PM7 through submerged fermentation.

Results
Initially, the traditional culture medium ISP2 was established as suitable for inoculum preparation, as it allowed high growth rates and consumption of ~ 75% reducing sugar, leading to 1.3 g L−1 dry biomass at 72 h of incubation. The formulated discarded potato broth (DPB) medium was evaluated together with five other traditional liquid culture media (potato dextrose broth, ISP2, ISP3, ISP4, and ISP5) for producing blue pigments by S. lydicus PM7. The highest blue pigment production was obtained by using DPB medium, reaching ~ 0.97 g L−1, followed by ISP5 (~ 0.36 g L−1). In terms of evaluating the concentration of discarded potato powder, the highest concentration of blue pigments was obtained with 16 g L−1, compared to concentrations of 4, 8, and 32 g L−1. In general, a notable increase in total proteins (~ 14 g L−1 in biomass; ~ 8 g L−1 in medium) and reducing sugars (~ 5 g L−1) on the fifth day of DPB fermentation was observed, at which time the production of blue pigments began. These data proved that S. lydicus PM7 is able to degrade potato wastes during submerged fermentation and to direct metabolism towards the formation of biopigments. Chromatographic analysis revealed that the main blue pigment produced by new strain in this complex medium is actinorhodin.

Conclusions
Discarded potato favored the production of blue pigments by S. lydicus PM7 under submerged fermentation, leading to final product concentration almost three times higher than others traditional Streptomyces culture media. To the best of our knowledge, this is the first report on the production of actinorhodin by the specie S. lydicus, as well as on this pigment synthesis based on an agricultural waste as a sole nutrient source for fermentation process. The findings showed that potato waste could be a potential byproduct for replacement of commercial culture media using for this same purpose.

Graphical Abstract
A new strategy for fabricating a stacked flexible capacitive sensor
Authors: Zhu Yuanxiang , Wu Daming , Jiang Haohua , Zhang Weile , Shen Lihao , Sun Jingyao , Zhuang Jian , Xu Hong , Huang Yao 
Published: July 2024

AbstractCurrently, flexible capacitive sensors have a wide range of application scenarios in the field of wearable electronic devices. In order to detect more subtle joint movements of the human body, a method of fabricating stacked capacitive sensors is demonstrated. An ultrathin dielectric elastomer film of about 110 μm by the “secondary calendering” method was prepared. The shape of the electrode layers was designed, printed the electrode materials on the dielectric elastomer film by screen-printing, realized the stacked-layer technology, and connected each sensor unit in parallel by the electrode columns formed inside. A 12-layer flexible capacitive sensor with an initial capacitance of 10.2nF, good resolution (1% strain), high sensitivity (1.09) and stability under 10,000 cycles is fabricated. The sensor fabricated in this paper can recognize the motion at various joints of the human body, such as elbow and knee joints. This paper provides a new method for fabrication of stacked flexible capacitive sensors, which opens up new applications in flexible sensors, wearable electronic devices and human-computer interaction.
Engineering cyanobacteria for the production of aromatic natural products
Authors: Gu Fei , Li Chaofeng , Zheng Haotian , Ni Jun 
Published: July 2024

AbstractAromatic natural products are important for improving human health and quality of life. Large-scale availability of these compounds from plants is limited by low yield and cumbersome extraction. Building high-performance microbial cell factories to produce aromatic natural products by means of metabolic engineering and synthetic biology is a viable option. In the context of climate change and global resource scarcity, choosing solar-powered and carbon-fixing microbial cyanobacteria instead of chemical heterotrophic microorganisms to produce aromatic compounds might be a more progressive and better solution. In this review, we summarize the principal strategies for improving the production of aromatic natural products in engineered cyanobacteria, including regulation of metabolism, optimization of synthetic pathway, culture process development, and microbial cooperation, highlighting the potential and availability of this microbe as a novel chassis cell.
A case-history using gravity data to validate alternate interpretations of the material below a deep seismic reflector in the Matheson area of Ontario, Canada
Authors: Della Justina Fabiano , Smith Richard S. , Haugaard Rasmus 
Published: July 2024

Gravity data are ‘nonunique’ in that a gravity anomaly can be explained by many bodies with different properties. Similarly, in seismic data, the strength of a reflection is dependent on the product of the density and the seismic velocity, so the nature of a reflection cannot be used to determine the density below an interface when the velocity is unknown. In a previous gravity study, we had concentrated on shallow features (model α), which implicitly assumed that a number of deeper reflections were due to an anomalous layer, thick enough to cause reflections from its upper and lower surfaces that do not cancel and that the density above and below this thick layer were the same. An alternate possibility is that the material below some of the reflections is lower density material called the Deloro assemblage. In order to test this hypothesized model (model β), we reinterpreted the seismic sections and repeated the gravity study. In order to allow for the deeper low-density material and account for some shallower reflectors having Deloro below, we had to make the Porcupine assemblage, which is shallow and even lower density than the Deloro, thinner in places. We found that the gravity data could be explained with the Deloro assemblage below the reflectors. The top of this hypothesized Deloro assemblage varies from 7.5 km in the east to 3 km in the west of the study area. Both models and are consistent with the gravity and seismic data, but model is also consistent with the Deloro being mapped outcropping to the west of the study area and a strong reflector (a banded iron formation) often being observed at the top of the Deloro. Our case study illustrates that modelling and interpretation should often be revised when new information becomes known.
Musings and Meditations on the Edginess and Hatred of Forgiveness
Authors: Opondo Sam Okoth 
Published: July 2024

Heeding Frantz Fanon's thoughts on colonialism and forgiveness alongside his call for us to “turn over a new leaf . . . work out new concepts, and try to set afoot a new man,” this text-mediated meditation on the hatred of forgiveness contends with the question/quest of forgiveness and its relevance to our idea of Africa today. To attend to these ethical questions, the author assembles a textual montage by juxtaposing Wole Soyinka's The Burden of Memory, the Muse of Forgiveness lecture series (1997), with some reflections on for/giving from Nathalie Etoke's Melancholia Africana (2019), Jacques Derrida's deconstruction of forgiveness, and Pumla Gobodo-Madikizela's (2004) attempt to imagine and inhabit a postapartheid South Africa where forgiveness acts as an infinite responsibility to the other. As such, this text-mediated meditation engages the newness, closure, eruption or interruption of violence, and forgiveness characteristic of the African present alongside discourses on African memories of grievances and speculations about the Africa that is yet-to-come.
The rs4354668 polymorphism in the SLC1A2 gene for the EAAT2 glutamate transporter is associated with an increased risk of harmful drug use – an exploratory study on a university student population
Authors: Dawidowski Bartosz , Olejniczak Barbara , Groblińska Katarzyna , Knapińska Magdalena , Kozicka Urszula , Krasiński Michał , Kułak Anna , Grelecki Grzegorz , Czaplińska Zuzanna , Piotrowska Oliwia , Kościelecka Klaudia , Podwalski Piotr , Michalczyk Anna , Samochowiec Jerzy 
Published: July 2024

Cel pracyDowody sugerują, że zmniejszone wydzielanie dopaminy w szlakach mezokortykolimbicznych może predysponować do zwiększonej podatności na uzależnienie od substancji psychoaktywnych. Zaproponowano zdefiniowanie takiego zjawiska jako zespołu deficytu nagrody (ang. reward deficiency syndrome, RDS). Badania wskazują, że zmniejszenie stymulującej transmisji glutaminergicznej w układzie dopaminergicznym może stanowić alternatywny fenotyp RDS. Potencjalnym źródłem tego typu nieprawidłowości jest wychwyt zwrotny glutaminianu, który zależy od funkcji transporterów aminokwasów pobudzających (ang. excitatory amino acid transporter, EAAT). Celem zaprezentowanego badania była ocena związku wariantów rs4354668 genu dla EAAT2 z ryzykiem wystąpienia zaburzeń związanych z używaniem substancji psychoaktywnych.MetodaPrzeanalizowaliśmy materiał genetyczny i dane psychometryczne 125 młodych dorosłych (n = 125) pod kątem wpływu polimorfizmu rs4354668 genu SLC1A2 dla EAAT2 na ryzykowne lub szkodliwe używanie narkotyków (ang. risky or harmful drug use, RHDU). Po analizie eksploracyjnej wykorzystaliśmy modele regresji logistycznej do oceny prawdopodobieństwa wystąpienia RHDU w poszczególnych grupach.WynikiW ostatecznym modelu wariant T/T rs4354668 był istotnie powiązany z niższym prawdopodobieństwem wystąpienia RHDU w porównaniu z wariantem G/G (OR: 0.021; 95% CI: 0.001 – 0.275; p = 0.009). Innymi istotnymi predyktorami RHDU były palenie tytoniu oraz ryzykowne lub szkodliwe picie alkoholu.WnioskiUzyskane wyniki mogą wskazywać na możliwy związek ryzyka szkodliwego używania narkotyków z wariantami polimorfizmu rs4354668 genu SLC1A2 dla EAAT2. Osoby z wariantem T/T tego polimorfizmu wydają się być mniej narażone na rozwój zaburzeń związanych z używaniem narkotyków.