bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated biorefinery for xylooligosaccharides, pectin, and bioenergy production from orange waste
Authors: Martins Manoela , Goldbeck Rosana 
Published: October 2023

AbstractOrange waste is one of the most underutilized biowastes. It accounts for 50% of the fruit weight after juice extraction, presenting an environmental problem due to inappropriate disposal. Industrial waste exploitation is a sustainable way to obtain bioproducts and bioenergy. However, the efficiency of chemical treatments and enzymatic cocktails is still a bottleneck in these processes. One potential route to reduce costs is to design consecutive extraction and hydrolysis stages to yield more products from different fractions of the same feedstock, reducing the use of time and bulk materials. This study assessed the economic performance of an orange processing waste (OPW) biorefinery for xylooligosaccharides (XOS), pectin, and bioenergy, involving three aspects: (1) experimental procedures, (2) a simulation approach, and (3) optimization tools. The optimization of hydrothermal treatment for pectin extraction decreased material costs by more than 60% and preserved the xylan content for xylooligosaccharide production by enzymatic hydrolysis. This study analyzed different biorefinery capacities, and solid waste exploitation for heat and steam generation, improving sustainability. The production cost per kg of high‐purity pectin and xylooligosaccharides is 3.67 $ with an efficient solvent recovery and self‐sufficiency for standard power usage. These results proved the economic feasibility and low environmental impact of the OPW biorefinery.
A facile route for highly enantioenriched six‐membered 1,4‐N,N‐ and N,O‐heterocycles from L‐serinate‐derived α‐bromoacetates
Authors: Lee So Jeong , Park Min Ji , Kim Seyeon , Park Yong Sun 
Published: October 2023

AbstractPreparation of highly enantioenriched six‐membered 1,4‐N,N‐ and N,O‐heterocycles has been developed through [4 + 2] heteroannulation of α‐bromoacetates with 1,4‐binucleophiles. Two consecutive substitutions of highly diastereoenriched L‐serinate‐derived α‐bromoacetates provide convenient access to a wide range of C‐aryl/aliphatic substituted 1,4‐N,N‐ and N,O‐heterocycles with up to 99:1 er.
The impact of epilepsy and antiseizure medications on pregnancy and neonatal outcomes: A nationwide cohort study
Authors: Kuo Cheng‐Yen , Kuo Chang‐Fu , See Lai‐Chu , Chiou Meng‐Jiung , Hung Po‐Cheng , Lin Jainn‐Jim , Lin Kuang‐Lin , Wang Huei‐Shyong , Chou I‐Jun 
Published: October 2023

AbstractPurposeOur objective was to assess the adverse outcomes during pregnancy, as well as for the fetus and neonates, in women with epilepsy, both with and without the use of antiseizure medications (ASMs).MethodsA cohort of singleton pregnancies between January 1, 2004 and December 31, 2014 was identified using the Taiwan National Health Database. The pregnancies were categorized into ASM exposure, ASM nonexposure, and control (consisting of women without an epilepsy diagnosis) groups. We recorded adverse outcomes in neonates and documented pregnancy complications. The generalized estimating equation with logit link was used to estimate adjusted odds ratios.ResultsThere were 629 singleton pregnancies in the group exposed to ASMs, 771 in the epilepsy group without ASM exposure, and 2,004,479 in the control group. Women with epilepsy had a significantly higher risk of puerperal cerebrovascular diseases (adjusted odds ratios in the exposure and nonexposure groups = 54.46 and 20.37, respectively), respiratory distress syndrome (5.1 and 2.99), mortality (3.15 and 3.22), sepsis (2.67 and 2.54), pregnancy‐related hypertension (1.71 and 1.8), preeclampsia (1.87 and 1.79), cesarean delivery (1.72 and 2.15), and preterm labor (1.38 and 1.56). The use of ASMs may increase the risk of eclampsia (adjusted odds ratio = 12.27). Compared to controls, fetuses/neonates born to women with epilepsy had a higher risk of unexplained stillbirth (adjusted odds ratios in the exposure and nonexposure groups = 2.51 and 2.37, respectively), congenital anomaly (1.37 and 1.33), central nervous system malformation (3.57 and 2.25), low birth weight (1.90 and 1.97), and a low Apgar score at 5 min (2.63 and 1.3). The use of ASMs may introduce an additional risk of small for gestational age; the adjusted odds ratio was 1.51.ConclusionWomen with epilepsy, irrespective of their exposure to ASMs, had a slightly elevated risk of pregnancy and perinatal complications. Puerperal cerebrovascular diseases may be a hidden risk for women with epilepsy.
Curcumin/L‐OHP co‐loaded HAP for cGAS‐STING pathway activation to enhance the natural immune response in colorectal cancer
Authors: Xiao Yao , Guo Guohu , Wang Huaiming , Peng Bin , Lin Yinglin , Qu Gaowen , Li Ben , Jiang Zhaojun , Zhang Fan , Wu Jiaming , Liang Min 
Published: October 2023

AbstractInsufficient immune cell infiltration into the tumor microenvironment (TME) greatly compromises the clinical application of immune‐checkpoint inhibitors (ICIs)‐based immunotherapy. Recent findings have shown that activation of the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway can enhance natural immunity and increase lymphocyte infiltration into the TME, which presents a promising strategy for cancer immunotherapy. In this study, we constructed hydroxyapatite nanoparticles co‐loaded with curcumin and L‐oxaliplatin (Cur/L‐OHP@HAP NPs). We analyzed the particle‐size distribution, zeta potential, spectral characteristics (Fourier‐transform infrared spectroscopy, X‐ray photoelectron spectroscopy, ultraviolet–visible spectroscopy), and drug‐release properties of the Cur/L‐OHP@HAP NPs. The cellular uptake of the Cur/L‐OHP@HAP NPs detected by flow cytometry and confocal laser‐scanning microscopy. We comprehensively evaluated the anti‐tumor properties and immune‐activating effects of the NPs, both in vitro and in vivo. Physicochemical characterizations demonstrated that the Cur/L‐OHP@HAP NPs were successfully synthesized and were capable of pH‐dependent drug release. Notably, the Cur/L‐OHP@HAP NPs efficiently entered cancer cells, after which the released L‐OHP induced nuclear DNA (nDNA) damage to some extent. HAP promoted the release of intracellular Ca2+ stores in cancer cells, and curcumin inhibited Ca2+ efflux, resulting in intracellular Ca2+ overload and the release of mitochondrial DNA (mtDNA). Damage to both nDNA and mtDNA greatly stimulated the cGAS‐STING pathway, thereby activating natural immunity, accompanied by immune cell recruitment to the TME. In summary, the Cur/L‐OHP@HAP NPs show good prospects for improving cancer immunotherapy.
Prodrug Rewards in Medicinal Chemistry: An Advance and Challenges Approach for Drug Designing
Authors: Husain Asif , Monga Jyoti , Narwal Smita , Singh Gurvirender , Rashid Mohammad , Afzal Obaid , Alatawi Abdurahhman , Almadani Norah M 
Published: October 2023

AbstractThis article emphasizes the importance of prodrugs and their diverse spectrum of effects in the field of developing novel drugs for a variety of biological applications. Prodrugs are chemicals that are supplied inactively, but then go through enzymatic and chemical transformation in vivo to release the active parent medication that can have the desired pharmacological effect. By adding an inactive chemical moiety, prodrugs are improved in a number of ways that contribute to their potency and durability. For the purpose of illustrating the usefulness of the prodrug approach, this review covers examples of prodrugs that have been made available or are now undergoing human trials. Additionally, it included lists of the most common functional groups, carrier linkers, and reactive chemicals that can be used to create prodrugs. The current study also provides a brief introduction, several chemical methods and modifications for creating prodrugs and mutual prodrugs, as well as an explanation of recent advancements and difficulties in the field of prodrug design. The primary chemical carriers employed in the creation of prodrugs, such as esters, amides, imides, NH‐acidic carriers, amines, alcohols, carbonyl, carboxylic, and azo‐linkages, are also discussed. This review also discusses glycosidic and triglyceride mutually activated prodrugs, which aim to deliver the drugs after bioconversion at the intended site of action. The article also discusses the extensive chemistry and wide variety of applications of recently approved prodrugs, such as antibacterial, anti‐inflammatory, cardiovascular, antiplatelet, antihypertensive, atherosclerotic, antiviral, etc. In order to illustrate the prodrug and mutual drug concept's various applications and highlight its many triumphs in overcoming the formulation and delivery of problematic pharmaceuticals, this work represents a thorough guide that includes the synthetic moiety for the reader.
Development of Ruthenium Nanophotocages with Red or Near‐Infrared Light‐Responsiveness
Authors: Zhang Zongwei , He Maomao , Wang Ran , Fan Jiangli , Peng Xiaojun , Sun Wen 
Published: October 2023

AbstractThe development of light‐triggered ruthenium (Ru) nanophotocages has revolutionized conventional methods of drug administration, thereby facilitating cancer therapy in a noninvasive and temperate manner. Ru nanophotocages employ a distinct approach known as photoactivated chemotherapy (PACT), wherein light‐induced ligand dissociation yields a toxic metal complex or a ligand capable of performing other functions such as optically controlled protein degradation and drug delivery. Simultaneously, this process is accompanied by the generation of reactive oxygen species (ROS), which serve as an effective anticancer agent in combination with PACT and photodynamic therapy (PDT). Due to its exceptional attributes of extended tissue penetration, and minimized tissue damage, red light or near‐infrared light is widely acknowledged as the “phototherapeutic window” (650–900 nm). In this Concept, we present an overview of the most recent advancements in Ru nanophotocages within the phototherapeutic range. Diverse aspects, including design principles, photocaging efficacy, photoactivation mechanisms, and potential applications in the field of biomedical chemistry, are discussed. Questions and challenges regarding their synthesis, characterization, and applications are also discussed. This Concept would foster further exploration into the realm of Ru nanophotocages.
Hybrid assessment of fiber orientation influence on the load resistance of anchors in SFRC
Authors: Mellios Nikolaos , Losse Jeffrey , Spyridis Panagiotis 
Published: October 2023

AbstractThe consistent evolution of concrete has led to a variety of concrete types that enhance the material's versatility, cost‐efficiency, and sustainability. Despite the rapid development and extensive research regarding steel fiber‐reinforced concrete (SFRC) in the last decades, there are still knowledge gaps on the material's resistance against locally applied tension loads on anchor bolts, as well as the interaction of possible nonhomogeneous fiber orientations on the anchorage axisymmetric stress field. This aspect becomes particularly relevant since anchors are placed at the component boundaries, where fibers tend to align parallel to the external surface. Through an innovative experimental investigation on 64 single‐bonded anchors using layer‐casting concrete and a supporting set of nonlinear finite element simulations, this work aspires to exhibit the influence of controlled unidimensional fiber orientation on the load‐bearing capacity and behavior of anchorages in SFRC.
Long‐term multimorbidity trajectories in older adults: The role of cancer, demographics, and health behaviors
Authors: Rees‐Punia Erika , Masters Matthew , Teras Lauren R. , Leach Corinne R. , Williams Grant R. , Newton Christina C. , Diver W. Ryan , Patel Alpa V. , Parsons Helen M. 
Published: October 2023

AbstractBackgroundMultimorbidity is associated with premature mortality and excess health care costs. The burden of multimorbidity is highest among patients with cancer, yet trends and determinants of multimorbidity over time are poorly understood.MethodsVia Medicare claims linked to Cancer Prevention Study II data, group‐based trajectory modeling was used to compare National Cancer Institute comorbidity index score trends for cancer survivors and older adults without a cancer history. Among cancer survivors, multinomial logistic regression analyses evaluated associations between demographics, health behaviors, and comorbidity trajectories.ResultsIn 82,754 participants (mean age, 71.6 years [SD, 5.1 years]; 56.9% female), cancer survivors (n = 11,265) were more likely than older adults without a cancer history to experience the riskiest comorbidity trajectories: (1) steady, high comorbidity scores (remain high; odds ratio [OR], 1.36; 95% CI, 1.29–1.45), and (2) high scores that increased over time (start high and increase; OR, 1.51; 95% CI, 1.38–1.65). Cancer survivors who were physically active postdiagnosis were less likely to fall into these two trajectories (OR, 0.73; 95% CI, 0.64–0.84, remain high; OR, 0.42; 95% CI, 0.33–0.53, start high and increase) compared to inactive survivors. Cancer survivors with obesity were more likely to have a trajectory that started high and increased (OR, 2.83; 95% CI, 2.32–3.45 vs. normal weight), although being physically active offset some obesity‐related risk. Cancer survivors who smoked postdiagnosis were also six times more likely to have trajectories that started high and increased (OR, 6.86; 95% CI, 4.41–10.66 vs. never smokers).ConclusionsOlder cancer survivors are more likely to have multiple comorbidities accumulated at a faster pace than older adults without a history of cancer. Weight management, physical activity, and smoking avoidance postdiagnosis may attenuate that trend.
Developmental profile of microglia distribution in nuclei of the superior olivary complex
Authors: Zacher Alina C. , Hohaus Kiara , Felmy Felix , Pätz‐Warncke Christina 
Published: October 2023

AbstractIn the brain, microglia are involved in immune responses and synaptic maturation. During early development, these cells invade the brain, proliferate, and morphologically mature to achieve coverage of the surrounding tissue with their fine processes. Their developmental proliferation overlaps with the postnatal development of neuronal circuits. Within the superior olivary complex (SOC), an auditory brainstem structure, microglia, and their early postnatal development have been documented. A quantification over the full developmental profile of the arrangement and morphological changes in single microglia cells is missing. Here, we used immunofluorescence labeling to quantify their distribution, morphological changes, and coverage during early and late postnatal development in the SOC of Mongolian gerbils. Microglia distributed rather homogenously within each nucleus with a bias to the nucleus borders at postnatal day (P) 5 and more centrally in the nucleus in mature stages. We found a nucleus‐specific transient increase in microglia cell number and density reaching its peak at P17 with a subsequent decline to P55 values. Length and branching of microglia protrusions increased especially after P12. The stronger ramification together with the increase in cell density allows coverage of the surrounding tissue from P5 to mature stages, despite the large developmental increase in nucleus size. The transient increase in density during synaptic refinement in SOC nuclei suggests that microglia are important during the pruning period, compensating for developmental increase in tissue volume, and that in mature stages their main function appears tissue surveillance.
Exploring and validating observations of non‐local species in eDNA samples
Authors: Westerduin Coen , Suokas Marko , Petäjä Tuukka , Saarela Ulla , Vainio Seppo , Mutanen Marko 
Published: October 2023

AbstractThe development of DNA‐based methods in recent decades has opened the door to numerous new lines of research in the biological sciences. While the speed and accuracy of DNA methodologies are clearly beneficial, the sensitivity of these methods has the adverse effect of increased susceptibility to false positives resulting from contamination in field or lab. Here, we present findings from a metabarcoding study on the diet of and food availability for five insectivorous birds, in which multiple lepidopteran species not known to occur locally were discovered. After describing the pattern of occurrences of these non‐local species in the samples, we discuss various potential origins of these sequences. First, we assessed that the taxonomic assignments appeared reliable, and local occurrences of many of the species could be plausibly ruled out. Then, we looked into the possibilities of natural environmental contamination, judging it to be unlikely, albeit impossible to fully falsify. Finally, while dissimilar combinations of non‐local species' occurrences across the samples did not initially suggest lab contamination, we found overlap with taxa and sequences handled in the same lab, which was undoubtedly not coincidental. Even so, not all exact sequences were accounted for in these locally conducted studies, nor was it clear if these and other sequences could remain detectable years later. Although the full explanation for the observations of non‐local species remains inconclusive, these findings highlight the importance of critical examination of metabarcoding results, and showcase how species‐level taxonomic assignments utilizing comprehensive reference libraries may be a tool in detecting potential contamination events, and false positives in general.
Diversity of freshwater algal assemblages across the United States as revealed by DNA metabarcoding
Authors: Schulte Nicholas O. , Craine Joseph M. , Leopold Devin R. , Devitt Jessica K. , Fierer Noah 
Published: October 2023

AbstractAs freshwater algae respond strongly to environmental conditions, algal communities are routinely used as indicators of aquatic health. Algal bioassessments have historically relied upon microscopy‐based identifications that are typically slow, expensive, taxonomically restricted, and inconsistent across analysts and time. Metabarcoding of water column DNA (environmental DNA, or eDNA) can characterize assemblages more quickly, at lower cost, and with higher taxonomic precision than microscopy. As such, eDNA metabarcoding has the potential to improve bioassessments, but relationships between environmental conditions and eDNA‐derived algal assemblage composition need to be determined first. We performed metabarcoding of a plastid 23S rRNA gene region for 1230 freshwater eDNA samples collected from 51 lakes and 617 streams across the conterminous United States to test for assemblage‐wide patterns that may indicate ecological condition. Samples were collected by citizen, academic, and research scientists using a standardized commercial kit. This effort constitutes the largest published water column eDNA survey yet of algal diversity across freshwaters in the United States. We detected 14,943 algal exact sequence variants (ESVs) from 11 divisions. The richness and abundance of cyanobacteria was higher in lakes, while streams were dominated by diatoms. Nationwide, only 1% of variation in stream assemblages was explained by catchment integrity. The remaining, explicable 19% was associated with forest cover, stream order, elevation, and broad‐scale spatial variables. Nevertheless, select ESVs were candidate indicators of gradients in stream catchment integrity and possible eutrophication. Together, we show that algal eDNA metabarcoding has potential for measuring ecological condition relative to water quality. Yet, further sampling along anthropogenic gradients is needed before algal eDNA can be used for large‐scale biomonitoring in the United States. We also found that only 2% of algal ESVs could be assigned to U.S. morphospecies, highlighting the importance of building a more comprehensive reference sequence database to integrate existing morphospecies autecology with eDNA‐based bioassessments.
CD95L concatemers highlight different stoichiometries of CD95‐mediated apoptotic and nonapoptotic pathways
Authors: Lebrault Eden , Oblet Christelle , Kurma Keerthi , Levoin Nicolas , Jeannet Robin , Jean Mickael , Vacher Pierre , Legembre Patrick 
Published: October 2023

AbstractTo better understand the stoichiometry of CD95L required to trigger apoptotic and nonapoptotic signals, we generated several CD95L concatemers from dimer to hexamer conjugated via a flexible link (GGGGS)2. These ligands reveal that although the hexameric structure is the best stoichiometry to trigger cell death, a dimer is sufficient to induce the apoptotic response in CD95‐sensitive Jurkat cells. Interestingly, only trimeric and hexameric forms can implement a potent Ca2+ response, suggesting that while CD95 aggregation controls the implementation of the apoptotic signal, both aggregation and conformation are required to implement the Ca2+ pathway.
Somatotopic disruption of the functional connectivity of the primary sensorimotor cortex in complex regional pain syndrome type 1
Authors: Hotta Jaakko , Saari Jukka , Harno Hanna , Kalso Eija , Forss Nina , Hari Riitta 
Published: October 2023

AbstractIn complex regional pain syndrome (CRPS), the representation area of the affected limb in the primary sensorimotor cortex (SM1) reacts abnormally during sensory stimulation and motor actions. We recorded 3T functional magnetic resonance imaging resting‐state data from 17 upper‐limb CRPS type 1 patients and 19 healthy control subjects to identify alterations of patients' SM1 function during spontaneous pain and to find out how the spatial distribution of these alterations were related to peripheral symptoms. Seed‐based correlations and independent component analyses indicated that patients' upper‐limb SM1 representation areas display (i) reduced interhemispheric connectivity, associated with the combined effect of intensity and spatial extent of limb pain, (ii) increased connectivity with the right anterior insula that positively correlated with the duration of CRPS, (iii) increased connectivity with periaqueductal gray matter, and (iv) disengagement from the other parts of the SM1 network. These findings, now reported for the first time in CRPS, parallel the alterations found in patients suffering from other chronic pain conditions or from limb denervation; they also agree with findings in healthy persons who are exposed to experimental pain or have used their limbs asymmetrically. Our results suggest that CRPS is associated with a sustained and somatotopically specific alteration of SM1 function, that has correspondence to the spatial distribution of the peripheral manifestations and to the duration of the syndrome.
Artificial intelligence for emergency medical care
Authors: Rajput Shivam , Sharma Pramod Kumar , Malviya Rishabha 
Published: October 2023

AbstractThere is increasing research into the potential benefits of incorporating artificial intelligence (AI) and machine learning algorithms into emergency medical services. AI is finding new applications across a wide range of sectors, one of which is healthcare, where it is being used to enhance clinical diagnostics. AI solutions have enormous untapped potential to improve healthcare efficiency and quality, thus researchers have focused heavily on emergency medicine (EM). Many individuals without prior experience with any physician often receive their initial medical care in the emergency room. Two areas that could benefit from the implementation of AI are reducing waiting times and enhancing diagnostic capabilities. This study provides further explanation of how AI is used in emergency rooms. Several machine learning‐based algorithms are also addressed. In this research, we summarise recent developments in the use of AI in EM. This research tries to summarise the usefulness of AI in EM by looking at recent developments in emergency department operations and clinical patient management.