bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimal purification method enables developability assessment of recombinant proteins
Authors: Rodriguez‐Aponte Sergio A. , Naranjo Christopher A. , Johnston Ryan S. , Dalvie Neil C. , Crowell Laura E. , Bajoria Sakshi , Kumru Ozan S. , Joshi Sangeeta B. , Volkin David B. , Love J. Christopher 
Published: March 2023

AbstractAnalytical characterization of proteins is a critical task for developing therapeutics and subunit vaccine candidates. Assessing candidates with a battery of biophysical assays can inform the selection of one that exhibits properties consistent with a given target product profile (TPP). Such assessments, however, require several milligrams of purified protein, and ideal assessments of the physicochemical attributes of the proteins should not include unnatural modifications like peptide tags for purification. Here, we describe a fast two‐stage minimal purification process for recombinant proteins secreted by the yeast host Komagataella phaffii from a 20 mL culture supernatant. This method comprises a buffer exchange and filtration with a Q‐membrane filter and we demonstrate sufficient removal of key supernatant impurities including host‐cell proteins (HCPs) and DNA with yields of 1–2 mg and >60% purity. This degree of purity enables characterizing the resulting proteins using affinity binding, mass spectrometry, and differential scanning calorimetry. We first evaluated this method to purify an engineered SARS‐CoV‐2 subunit protein antigen and compared the purified protein to a conventional two‐step chromatographic process. We then applied this method to compare several SARS‐CoV‐2 RBD sequences. Finally, we show this simple process can be applied to a range of other proteins, including a single‐domain antibody, a rotavirus protein subunit, and a human growth hormone. This simple and fast developability methodology obviates the need for genetic tagging or full chromatographic development when assessing and comparing early‐stage protein therapeutics and vaccine candidates produced in K. phaffii.
Long‐term follow‐up seizure outcomes after corpus callosotomy: A systematic review with meta‐analysis
Authors: Wu Xiaolong , Ou Siqi , Zhang Huaqiang , Zhen Yuhang , Huang Yinchun , Wei Penghu , Shan Yongzhi 
Published: March 2023

AbstractBackgroundCorpus callosotomy (CC) is appropriate for patients with seizures of a bilateral or diffuse origin, or those with seizures of a unilateral origin with rapid spread to the contralateral cerebral hemisphere. The efficiency of CC in patients with drug‐resistant epilepsy is a long‐term concern because most articles reporting the surgical results of CC arise from small case series, and the durations of follow‐up vary.MethodsPubMed, Embase, Cochrane Library, and Web of Science were searched to identify papers published before November 8, 2021. The systematic review was completed following PRISMA guidelines. Outcomes were analyzed by meta‐analysis of the proportions.ResultsA total of 1644 patients with drug‐resistant epilepsy (49 retrospective or prospective case series studies) underwent CC, and the follow‐up time of all patients was at least 1 year. The rate of complete seizure freedom (SF) was 12.38% (95% confidence interval [CI], 8.17%–17.21%). Meanwhile, the rate of complete SF from drop attacks was 61.86% (95% CI, 51.87%–71.41%). The rates of complete SF after total corpus callosotomy (TCC) and anterior corpus callosotomy (ACC) were 11.41% (95% CI, 5.33%–18.91%) and 6.75% (95% CI, 2.76%–11.85%), respectively. Additionally, the rate of complete SF from drop attacks after TCC was significantly higher than that after ACC (71.52%, 95% CI, 54.22%–86.35% vs. 57.11%, 95% CI, 42.17%–71.49%). The quality of evidence for the three outcomes by GRADE assessment was low to moderate.ConclusionThere was no significant difference in the rate of complete SF between TCC and ACC. TCC had a significantly higher rate of complete SF from drop attacks than did ACC. Furthermore, CC for the treatment of drug‐resistant epilepsy remains an important problem for further investigation because there are no universally accepted standardized guidelines for the extent of CC and its benefit to patients. In future research, we will focus on this issue.
Acid sphingomyelinase (ASM) and COVID‐19: A review of the potential use of ASM inhibitors against SARS‐CoV‐2
Authors: Pauletto Pedro José Tronco , Delgado Cassia Pereira , da Rocha João Batista Teixeira 
Published: March 2023

AbstractIn the last 2 years, different pharmacological agents have been indicated as potential inhibitors of SARS‐CoV‐2 in vitro. Specifically, drugs termed as functional inhibitors of acid sphingomyelinase (FIASMAs) have proved to inhibit the SARS‐CoV‐2 replication using different types of cells. Those therapeutic agents share several chemical structure characteristics and some well‐known representatives are fluoxetine, escitalopram, fluvoxamine, and others. Most of the FIASMAs are primarily used as effective therapeutic agents to treat different pathologies, therefore, they are natural drug candidates for repositioning strategy. In this review, we summarize the two main proposed mechanisms mediating acid sphingomyelinase (ASM) inhibition and how they can explain the inhibition of SARS‐CoV‐2 replication by FIASMAs. The first mechanism implies a disruption in the lysosomal pH fall as the endosome–lysosome moves toward the interior of the cell. In fact, changes in cholesterol levels in endosome–lysosome membranes, which are associated with ASM inhibition is thought to be mediated by lysosomal proton pump (ATP‐ase) inactivation. The second mechanism involves the formation of an extracellular ceramide‐rich domain, which is blocked by FIASMAs. The ceramide‐rich domains are believed to facilitate the SARS‐CoV‐2 entrance into the host cells.
Mechanocatalysis: Simple and Rapid Mechanochemical Synthesis of Ammonia in Hydrogen, Nitrogen, and Water System
Authors: He Chengli , Hao Zixiang , Wang Linrui , Qiu Dong , Wang Mingyan , Chen Yang , Cui Xiaoli 
Published: March 2023

AbstractMechanical force‐induced N2 fixation is an emerging strategy for single‐step ammonia synthesis under room temperature and atmospheric pressure. Here, we demonstrate a simple and rapid approach to synthesize NH3 in the N2+H2+H2O system and illustrate the reaction mechanism by theoretical calculations. The NH3 generation rate can reach 2.847 mg L−1 h−1 with an NH4+ selectivity of 99.45 wt.%. The presence of H2 can inhibit oxidation reactions to form NO3− by‐products and promote proton generation from H2O dissociation. The calculated formation energy of H‐adatom and OH‐adatom from H2O cleavage is −2.86 eV in N2+H2+H2O system, much lower than that in N2+H2O system, verifying much easier dissociation of H2O molecules and significantly facilitated proton generation to enlarge the NH4+ yield. This work provides a simple approach to improve mechanochemical N2 fixation performance and highlights a proton generation enhancement mechanism.
Electrochemical Determination of Flap Endonuclease 1 Activity Amplified by CRISPR/Cas12a Trans‐Cleavage**
Authors: Zhu Yulin , Zhu Jinwen , Gao Yan , Shi Jiayue , Miao Peng 
Published: March 2023

AbstractFlap endonuclease 1 (FEN1) participates in the DNA replication and repair processes, which plays an important role in maintaining genome stability. Determination of FEN1 level is highly required for biochemical studies and clinical diagnosis. Herein, a novel electrochemical approach for the detection of FEN1 is developed based on clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR‐associated (Cas) proteins trans‐cleavage. The dumbbell structured DNA substrate, single‐stranded DNA labelled with electrochemical species and three‐dimensional tetrahedral DNA are designed and involved in the reactions. This method displays high sensitivity and good specificity, which can not only monitor FEN1 in various biological samples directly, but also help screen FEN1 inhibitors with potential use for anti‐cancer drug discovery.
Intermetallic Compound TiM (M=Co, Fe) with a Layered Structure Prepared by Deoxidizing Ilmenite‐type Oxides in Molten LiCl‐CaH2 Mixtures
Authors: Kobayashi Yasukazu , Nagaura Tomota , Alowasheeir Azhar , Tada Shohei , Yamauchi Yusuke 
Published: March 2023

AbstractCsCl‐type intermetallic compounds TiM (M=Co, Fe) were obtained by deoxidizing trigonal ilmenite‐type MTiO3 with a reducing agent CaH2 in molten LiCl at 600 °C. X‐ray diffraction, nitrogen adsorption, scanning electron microscopy, and transmission electron microscopy with energy‐dispersive X‐ray, and X‐ray photoelectron spectroscopy analyses revealed the formation of nanoscale layered structures, which enhanced specific surface areas (approximately 20 m2/g) in the intermetallic compounds. In the initial deoxidation stage, Li2TiO3‐like compounds were observed as an intermediate, suggesting the substitution of M in MTiO3 by Li from the molten LiCl. Compound MTiO3 has a layered structure perpendicular to the c axis of the trigonal structure, suggesting that the layered structures may originate from the crystal structure of the precursors. Formation of the Li2TiO3‐like intermediate may help maintain the original layered structure during deoxidation and the subsequent alloying at temperatures as low as 600 °C.
Structural and Synthetic Insights on Oxidative Homocouplings of Alkynes Mediated by Alkali‐Metal Manganates
Authors: Mastropierro Pasquale , Platten Andrew W. J. , Kennedy Alan R. , Hevia Eva , Uzelac Marina 
Published: March 2023

AbstractExploiting bimetallic cooperation alkali‐metal manganate (II) complexes can efficiently promote oxidative homocoupling of terminal alkynes furnishing an array of conjugated 1,3‐diynes. The influence of the alkali‐metal on these C−C bond forming processes has been studied by preparing and structurally characterizing the alkali‐metal tetra(alkyl) manganates [(TMEDA)2Na2Mn(CH2SiMe3)4] and [(PMDETA)2K2Mn(CH2SiMe3)4]. Reactivity studies using phenylacetylene as a model substrate have revealed that for the homocoupling to take place initial metalation of the alkyne is required. In this regard, the lack of basicity of neutral Mn(CH2SiMe3)2 precludes the formation of the diyne. Contrastingly, the tetra(alkyl) alkali‐metal manganates behave as polybasic reagents, being able to easily deprotonate phenylacetylene yielding [{(THF)4Na2Mn(C≡CPh)4}∞] and [(THF)4Li2Mn(C≡CPh)4]. Controlled exposure of [{(THF)4Na2Mn(C≡CPh)4}∞] and [(THF)4Li2Mn(C≡CPh)4] to dry air confirmed their intermediary in formation of 1,4‐diphenyl‐1,3‐butadiyne in excellent yields. While the Na/Mn(II) partnership proved to be the most efficient in stoichiometric transformations, under catalytic regimes, the combination of MC≡CAr (M= Li, Na) and MnCl2 (6 mol %) only works for lithium, most likely due to the degradation of alkynylsodiums under the aerobic reaction conditions.
Teicoplanin aglycone media and carboxypeptidase Y: Tools for finding low‐abundance D‐amino acids and epimeric peptides
Authors: Sung Yu‐Sheng , Khvalbota Liudmyla , Dhaubhadel Umang , Špánik Ivan , Armstrong Daniel W. 
Published: March 2023

AbstractD‐amino acids and epimeric peptides/proteins can play crucial biological roles and adversely affect protein folding and oligopeptide aggregation in age‐related pathologies in humans. This has ignited interest in free D‐amino acids as well as those incorporated in peptides/proteins and their effects in humans. However, such stereoisomeric analytes are often elusive and in low abundance with few existing methodologies capable of scouting for and identifying them. In this work, we examine the feasibility of using teicoplanin aglycone, a macrocyclic antibiotic, which has been reported to strongly retain D‐amino acids and peptides with a D‐amino acid on the C‐terminus, for use as a solid phase extraction (SPE) medium. The HPLC retention factors of L‐/D‐amino acids and C‐terminus modified D‐amino acid‐containing peptides and their L‐amino acid exclusive counterparts on teicoplanin aglycone are presented. Retention curve differences between amino acids and peptides highlight regions of solvent composition that can be utilized for their separation. This approach is particularly useful when coupled with enzymatic hydrolysis via carboxypeptidase Y to eliminate all L‐amino acid exclusive peptides. The remaining peptides with carboxy‐terminal D‐amino acids are then more easily concentrated and identified.
Co‐Digestion of Water Hyacinth and Duck Manure for Potential Low‐Cost Biogas Production by Rural Communities
Authors: Jamaluddin Julaikha , Zulkeflee Zufarzaana 
Published: March 2023

AbstractLeftover harvested water hyacinth biomass and duck manure can create waste management issues. As they are readily abundant and available, potential co‐digestion of both waste sources for biogas production is explored as a waste‐to‐energy approach for a rural fishermen community. Seven 19‐L do‐it‐yourself bioreactors are constructed with four different feedstock mixing ratios. The mixing ratios of water hyacinth to duck manure are varied at 70:30, 50:50, and 30:70, and are conducted in duplicate. One reactor utilizing 100% water hyacinth as feedstock acts as the control. Biogas production is measured daily for 50 days through the water displacement method. Variations in pH and chemical oxygen demand levels are monitored weekly. The results show that the highest biogas production is from the mixture of water hyacinth to duck manure at a 70:30 ratio (p < 0.05), with a volume of cumulative gas produced at 4.27 L that can be well simulated through the logistic function kinetic model (R2 = 0.965). The biogas produced consists of methane, carbon monoxide, and hydrogen sulfide. The findings prove the potential of water hyacinth and duck manure as feedstocks for biogas production as one of the waste management solutions that can be practiced by the community.
Clinical implications of tumor‐based next‐generation sequencing in high‐grade epithelial ovarian cancer
Authors: Foster Katherine I. , Shaw Kenna R. M. , Jin Jeff , Westin Shannon N. , Yap Timothy A. , Glassman Deanna M. , Jazaeri Amir A. , Rauh‐Hain Jose A. , Lee Sanghoon , Fellman Bryan M. , Ju Zhenlin , Liu Yuexin , Fleming Nicole D. , Sood Anil K. 
Published: March 2023

AbstractBackgroundTumor‐based next‐generation sequencing is used inconsistently as a tool to tailor treatment of ovarian cancer, yet beyond detection of somatic BRCA1 and BRCA2 mutations, the clinical benefit is not well established. This study aimed to assess the clinical relevance of tumor‐based next‐generation sequencing (tbNGS) in patients with ovarian cancer.MethodsThis retrospective study included patients with high‐grade epithelial ovarian carcinoma. tbNGS results were identified in the electronic medical record using optical character recognition and natural language processing. Genetic, clinical, and demographic information was collected. Progression‐free survival (PFS) and overall survival were calculated and compared using log‐rank tests. Multivariate Cox regression and clustering analyses were used to identify patterns of genetic alterations associated with survival.ResultsOf 1092 patients in the described population, 409 (37.5%) had tbNGS results. Nearly all (96.1% [393/409]) had one or more genetic alterations. In 25.9% (106/409) of patients, an alteration that aligned with a targeted treatment was identified, and in an additional 48.7% (199/409), tbNGS results suggested eligibility for an investigational agent or clinical trial. The most frequent alterations were TP53, PIK3CA, and NF1 mutations, and CCNE1 amplification. Together, BRCA1 and BRCA2 mutations were associated with longer PFS (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.42–0.92; p = .02), whereas AKT2 amplification was associated with shorter PFS (HR, 3.86; 95% CI, 1.002–14.88; p < .05). Multivariate Cox regression and clustering analyses identified several combinations of genetic alterations that corresponded to outcomes in patients with high‐grade serous carcinoma.ConclusionstbNGS often yields clinically relevant information. Detailed analysis of population‐level tumor genomics may help to identify therapeutic targets and guide development of clinical decision support tools.Plain Language Summary

Although more and more patients with ovarian cancer are undergoing tumor‐based next‐generation sequencing to identify genetic mutations in their tumors, the benefits of such testing are not well established.

In a group of over 400 patients with ovarian cancer who underwent tumor‐based next‐generation sequencing in the course of their treatment, nearly all patients had one or more genetic alterations detected, and one out of four patients had a mutation that qualified them for a personalized treatment option.
Stage I epithelial or stromal type Wilms tumors are low risk tumors: An analysis of patients treated on the SIOP‐WT‐2001 protocol in the UK‐CCLG and GPOH studies (2001–2020)
Authors: D’Hooghe Ellen , Furtwängler Rhoikos , Chowdhury Tanzina , Vokuhl Christian , Al‐Saadi Reem , Pritchard‐Jones Kathy , Graf Norbert , Vujanić Gordan M. 
Published: March 2023

AbstractBackgroundPatients treated with preoperative chemotherapy with stage I intermediate‐risk Wilms tumor (IR‐WT) represent the largest group of patients with Wilms tumor (WT), and they have excellent outcomes.MethodsThe authors performed a retrospective analysis of patients with stage I epithelial (ET‐WT) or stromal type WT (ST‐WT) treated pre‐ and postoperatively according to the International Society of Paediatric Oncology‐WT‐2001 protocol in the UK Children's Cancer and Leukaemia Group and Gesellschaft für Pädiatrische Onkologie und Hämatologie groups' participation in the relevant WT trials and studies (2001–2020).ResultsThere were 880 patients with stage I IR‐WT, including 124 with ET‐WT, 156 with ST‐WT, and 600 with other IR‐WT (oIR‐WT). Patients with stage I ET‐WT or ST‐WT were significantly younger than patients with oIR‐WT, represented a large proportion of stage I WTs in their groups, and tumors showed poor histologic response to preoperative chemotherapy. The 5‐year event‐free survival (EFS) estimates for patients with stage I ET‐WT (96.8% ± 1.8 SE) or ST‐WT (96.8% ± 1.6 SE) were significantly better than for patients with oIR‐WT (90.3% ± 1.3 SE) (p = .014 and p = .009, respectively). A multivariate analysis showed that histologic type (ET‐WT or ST‐WT) remained a significant factor for EFS when adjusted for age and gender (p = .032 and p = .022, respectively). In both groups, relapses occurred in 3.2% of patients, and the overall survival was 99.2%.ConclusionsThe results suggest that stage I ET‐WT or ST‐WT could be regarded as low‐risk WT, for which omission of postoperative chemotherapy should be considered.Plain Language Summary

Patients with pretreated intermediate‐risk Wilms tumor (WT) represent the largest group of patients with WT.

This study reports the outcomes of patients with stage I epithelial type (ET‐WT) or stromal type WT (ST‐WT).

These patients were significantly younger and had a larger proportion of stage I cases than patients with other intermediate‐risk WT (oIR‐WT).

The event‐free survival for patients with stage I ET‐WT and ST‐WT was significantly better than for patients with oIR‐WT.

Rare relapses were curable resulting in 99.2% overall survival.
An adjoint‐based method for the computation of gradients in coagulation schemes
Authors: Nicoud Franck 
Published: March 2023

AbstractAn adjoint‐based methodology is proposed to compute the gradient of the outcomes of mathematical models for the coagulation cascade. The method is first exposed and validated by considering a simple, analytically tractable case involving only 3 species. Its potential is further illustrated by considering a detailed model for the extrinsic pathway involving 34 chemical species interacting through 45 chemical reactions and for which the gradient of Endogeneous Thrombin Potential, clotting time, maximum rate and peak value of thrombin with respect to the initial concentrations and reactions rates are computed. It is shown that the method produces gradients estimates that are fully consistent with the finite differences approximation used so far in the literature, but at a much lower computational cost.
A state‐of‐the‐art survey of predicting students' performance using artificial neural networks
Authors: Xiao Wen , Hu Juan 
Published: March 2023

AbstractPredicting students' performance is one of the most important issue in educational data mining. In order to investigate the state‐of‐the‐art research development in predicting students' performance by using artificial neural networks (ANN), we conducted a survey on 39 important studies on this issue from 2016 to 2021. The results show that: (1) objectives of most prediction model is the performance of learners on the program and course; (2) datasets used for training prediction model are collected from logs of the learning management system; (3) the most commonly used ANN is feedforward neural network; (4) researchers use stochastic gradient descent and Adam algorithm to optimizes the parameters in ANN and configure hyper parameters of ANN manually; (5) feature selection is not necessary because ANN can automatically adjust the weights of artificial neurons; and (6) ANN has better performance than the classical classifiers in predicting student performance. The challenges in previous studies were comprehensively analyzed, suggestions for future research were put forward.
Neuropsychiatric profile in average intelligent individuals with coexisting epilepsy and psychogenic non‐epileptic seizures
Authors: Giugno Alessia , Martino Iolanda , Sammarra Ilaria , Fratto Enrico , Fortunato Francesco , Labate Angelo , Gambardella Antonio 
Published: March 2023

AbstractGlobal neuropsychological impairments with intellectual disability (ID) seem to play a major role in the occurrence of psychogenic non‐epileptic seizures (PNES) in epilepsy. Conversely, the pathophysiology underlying PNES combined with epilepsy without ID remains elusive. We investigated the neuropsychiatric profile in 26 average intelligent subjects (15 women, mean age: 40.04 ± 13.53 years) with temporal lobe epilepsy (TLE) plus PNES (TLE + PNES), compared with 28 with TLE and 22 with PNES alone, matched for age and sex. All subjects underwent neuropsychiatric assessment, including Beck Depression Inventory‐2 (BDI‐2), State‐Trait Anxiety Inventory (STAI), Dissociative Experiences Scale (DES), Toronto Alexithymia Scale (TAS‐20), Traumatic Experience Checklist (TEC), and cognitive evaluation. TLE + PNES and PNES groups shared a similar psychiatric profile with higher levels of depression (BDI‐2, P < 0.001), anxiety (STAI‐S, P < 0.001; STAI‐T, P < 0.001), dissociation (DES, P < 0.001), and alexithymia (TAS, P = 0.005) scales than the TLE group. Nonetheless, like individuals with TLE, patients with TLE + PNES had a lower rate of a potentially traumatizing event than PNES. The very low rate of potentially traumatizing event in subjects with TLE + PNES leads us to hypothesize that epilepsy itself may be the psychophysiological distress that contributed to PNES. A psychopathological assessment in subjects with epilepsy is crucial to identify those more likely to develop PNES.