bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent Advancements in the Early Diagnosis and Treatment of Alzheimer's Disease
Authors: Wu Ye , Fu Li , Li Qianqian , Gao Xiang , Zhang Yingjun , Jin Chuanfei , Ding Feiqing , Hong Sheng , Cai Hui , Li Yiliang 
Published: July 2023

AbstractAlzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia. Although it is discovered more than 100 years ago and is the subject of many scientific studies, much is yet to be discovered about many aspects of this disease, including the precise biological changes that cause it, the best approach to its early diagnosis, and effective therapeutic interventions to slow or stop the progression. This article briefly reviews the disease progression, risk factors, and pathogenesis of the disease. In addition, the current early diagnostic and therapeutical strategies for AD are presented.
Variation in fruit and seed dimensions is better explained by dispersal system than by leaf size in a tropical rainforest
Authors: Stevenson Pablo R. , Acosta‐Rojas Diana C. , Cárdenas Sasha , Francisco Henao‐Díaz L. 
Published: July 2023

AbstractPremiseVariation in fruit and seed traits could originate from selection pressures exerted by frugivores or other ecological factors (adaptive hypotheses) and developmental constraints (by‐product hypotheses) or chance.MethodsWe evaluated fruit and leaf traits for nearly 850 plant species from a rainforest in Tinigua Park, Colombia. Through a series of linear regressions controlling for the phylogenetic signal of the traits (minimum N = 542), we tested (1) whether the allometry between seed width and length depends on seed dispersal system (Mazer and Wheelwright's adaptive hypothesis of allometry for species dispersed in the guts of animals = endozoochory) and (2) whether fruit length is associated with leaf length (i.e., Herrera's by‐product hypothesis derived from the assumption that both organs develop from homologous structures).ResultsWe found a strong negative allometric association between seed width and length for seeds of endozoochorous species, as expected; but also, for anemochorous species. We found a positive relationship between fruit and leaf length, but this relationship was not evident for zoochorous species. Fruit size was highly correlated with seed size.ConclusionsThe allometry between seed length and width varied among dispersal systems, supporting that fruit and seed morphology has been modified by interactions with frugivores and by the possibility to rotate for some wind dispersed species. We found some support for the hypothesis on developmental constraints because fruit and leaf size were positively correlated, but the predictive power of the relationship was low (10–15%).
Asymmetric α‐Azidation Reaction of β‐Ketoesters Catalyzed by Chiral Tin Alkoxides
Authors: Yanagisawa Akira , Takagi Kotaro , Horiguchi Moe , Dezaki Kohei , Marui Tomoki , Saito Etsushi , Ebihara Toru , Russell Go M. , Watanabe Takamichi , Midorikawa Koji 
Published: July 2023

AbstractA catalytic enantioselective α‐azidation reaction of β‐ketoesters with an azidated hypervalent iodine reagent was achieved by using an (R)‐BINOL‐derived chiral tin dibromide possessing 4‐t‐butylphenyl groups at the 3‐ and 3’‐positions as the chiral precatalyst in the presence of sodium ethoxide and ethanol. Optically active α‐azido‐β‐ketoesters having a chiral tertiary carbon were obtained in moderate to high yields under the influence of the chiral tin diethoxide generated in situ.
Obexelimab in Systemic Lupus Erythematosus With Exploration of Response Based on Gene Pathway Co‐Expression Patterns: A Double‐Blind, Randomized, Placebo‐Controlled, Phase 2 Trial
Authors: Merrill Joan T. , Guthridge Joel , Smith Miles , June Joshua , Koumpouras Fotios , Machua Wambui , Askanase Anca , Khosroshahi Arezou , Sheikh Saira Z. , Rathi Gaurav , Burington Bart , Foster Paul , Matijevic Mark , Arora Sujata , Wang Xiaodong , Gao Minggeng , Wax Stephen , James Judith A. , Zack Debra J. 
Published: July 2023

ObjectiveObexelimab is an investigational, bifunctional, noncytolytic monoclonal antibody that binds CD19 and FcyRIIb to inhibit B cells, plasmablasts, and plasma cells. This trial evaluated the efficacy and safety of obexelimab in the treatment of patients with systemic lupus erythematosus (SLE).MethodsDuring screening, patients with active, non–organ‐threatening SLE received corticosteroid injections to ameliorate symptoms while immunosuppressants were withdrawn (≤10 mg/day prednisone equivalent and ≤400 mg/day hydroxychloroquine allowed). Patients with improved disease activity were randomized 1:1 to obexelimab 5 mg/kg intravenously or placebo once every 2 weeks until week 32 or loss of improvement (LOI).ResultsIn this study, 104 patients were randomized. Analysis of the primary endpoint, proportion of patients reaching week 32 without LOI, used an efficacy‐evaluable (EE) population defined as patients who completed the study or withdrew for flare or treatment‐related toxicity. This endpoint did not reach statistical significance: 21 of 50 obexelimab‐treated patients (42.0%) versus 12 of 42 patients (28.6%) treated with a placebo (P = 0.183). Time to LOI was increased in obexelimab‐treated patients versus patients treated with a placebo in the EE (hazard ratio [HR] 0.53, P = 0.025) and intention‐to‐treat (HR 0.59, P = 0.062) populations. In obexelimab‐treated patients, B cells decreased approximately 50%, and trough concentration and inclusion in baseline gene expression clusters with high B cell pathway modules were associated with increased time to LOI. Obexelimab was associated with infusion reactions but was generally safe and well‐tolerated.ConclusionAlthough the primary endpoint was not reached, secondary analysis showed time to LOI was significantly increased in obexelimab‐treated patients, and analysis of patient subsets defined by gene expression patterns at baseline suggests a responding subpopulation.image
Fe3O4 and bimetal–organic framework Zn/Mg composite peroxide‐like catalyze luminol chemiluminescence for specific measurement of atropine in Datura plant
Authors: Mahmoudi Shaida , Chaichi Mohamad Javad , Shamsipur Mojtaba , Nazari Ome Leila , Samadi‐Maybodi Abdolraouf 
Published: July 2023

AbstractAtropine (AT) is an anticholinergic drug. AT is abundantly in Datura plant seeds. Fe3O4@Zn/Mg MOF (Fe3O4@MOF) composite was synthesized. The compound had a high peroxidase‐like activity in a chemiluminescence (CL) reaction. Addition of AT quenched CL. The linear range and limit of detection were 5–600 μg L−1 and 2 × 10−2 μg L−1. This method is fast, reversible, and selective, without biodegradability effects, high accuracy, and precision for measuring AT in the Datura plant.
Synthesis of epitope‐targeting nanobody based on native protein–protein interactions for FtsZ filamentation suppressor
Authors: Nakazawa Hikaru , Katsuki Taiji , Matsui Takashi , Tsugita Atsushi , Yokoyama Takeshi , Ito Tomoyuki , Kawada Sakiya , Tanaka Yoshikazu , Umetsu Mitsuo 
Published: July 2023

AbstractPhage display and biopanning are powerful tools for generating binding molecules for a specific target. However, the selection process based only on binding affinity provides no assurance for the antibody's affinity to the target epitope. In this study, we propose a molecular‐evolution approach guided by native protein–protein interactions to generate epitope‐targeting antibodies. The binding‐site sequence in a native protein was grafted into a complementarity‐determining region (CDR) in the nanobody, and a nonrelated CDR loop (in the grafted nanobody) was randomized to create a phage display library. In this construction of nanobodies by integrating graft and evolution technology (CAnIGET method), suitable grafting of the functional sequence added functionality to the nanobody, and the molecular‐evolution approach enhanced the binding function to inhibit the native protein–protein interactions. To apply for biological tool with growth screening, model nanobodies with an affinity for filamenting temperature‐sensitive mutant Z (FtsZ) from Staphylococcus aureus were constructed and completely inhibited the polymerization of FtsZ as a function. Consequently, the expression of these nanobodies drastically decreased the cell division rate. We demonstrate the potential of the CAnIGET method with the use of native protein–protein interactions for steady epitope‐specific evolutionary engineering.
Structural brain morphology in young adult women who have been choked/strangled during sex: A whole‐brain surface morphometry study
Authors: Hou Jiancheng , Huibregtse Megan E. , Alexander Isabella L. , Klemsz Lillian M. , Fu Tsung‐Chieh , Rosenberg Molly , Fortenberry James Dennis , Herbenick Debby , Kawata Keisuke 
Published: July 2023

AbstractIntroductionBeing choked/strangled during partnered sex is an emerging sexual behavior, particularly prevalent among young adult women. Using a multiparameter morphometric imaging approach, we aimed to characterize neuroanatomical differences between young adult women (18–30 years old) who were exposed to frequent sexual choking and their choking naïve controls.MethodsThis cross‐sectional study consisted of two groups (choking [≥4 times in the past 30 days] vs. choking‐naïve group). Participants who reported being choked four or more times during sex in the past 30 days were enrolled in the choking group, whereas those without were assigned to the choking naïve group. High‐resolution anatomical magnetic resonance imaging (MRI) data were analyzed using both volumetric features (cortical thickness) and geometric features (fractal dimensionality, gyrification, sulcal depth).ResultsForty‐one participants (choking n = 20; choking‐naïve n = 21) contributed to the final analysis. The choking group showed significantly increased cortical thickness across multiple regions (e.g., fusiform, lateral occipital, lingual gyri) compared to the choking‐naïve group. Widespread reductions of the gyrification were observed in the choking group as opposed to the choking‐naïve group. However, there was no group difference in sulcal depth. The fractal dimensionality showed bi‐directional results, where the choking group exhibited increased dimensionality in areas including the postcentral gyrus, insula, and fusiform, whereas decreased dimensionality was observed in the bilateral superior frontal gyrus and pericalcarine cortex.ConclusionThese data in cortical morphology suggest that sexual choking events may be associated with neuroanatomical alteration. A longitudinal study with multimodal assessment is needed to better understand the temporal ordering of sexual choking and neurological outcomes.
Effects of STN‐DBS surgery on cerebral glucose metabolism and distribution of DAT in Parkinson's disease
Authors: Luo Ganhua , Shi Xinchong , Jiang LuLu , Wu Lei , Yi Chang , Xian Wenbiao , Liu Yanmei , Wen Fuhua , Qian Hao , Chen Jie , Fu Xiaoli , Liu Jinlong , Zhang Xiangsong , Chen Ling 
Published: July 2023

AbstractIntroduction: Parkinson's disease (PD) is a neurodegenerative disorder that affects millions of people worldwide. Subthalamic nucleus (STN) deep brain stimulation (DBS) has been shown to be an effective treatment for PD; however, the effects of this surgery on cerebral metabolism and presynaptic dopamine transporter (DAT) distribution are still being studied.Methods: In this study, we included 12 PD patients (6 male and 6 female) who underwent STN‐DBS surgery and had both 18F‐FDG and 11C‐CFT PET/CT imaging before and 1 year after the surgery. We used paired t‐tests to identify changes in cerebral metabolism and calculated PD‐related metabolic covariance pattern (PDRP) scores. We also assessed the uptake of 11C‐CFT in the striatum using striatal‐to‐occipital ratios (SORs).Results: One year after surgery, we observed significant reductions in tremor, rigidity, akinesia, postural instability/gait disturbance, and Unified Parkinson's Disease Rating Scale Part III scores (p < .01, p < .001, p < .001, p < .001, and p < .001, respectively). Hamilton Depression Rating Scale and quality of life (PDQ‐39 SI) were also significantly reduced (p < .05 and p < .01, respectively). The mean PDRP score decreased by 37% from 13.0 ± 6.6 to 8.2 ± 7.9 after STN‐DBS surgery (p < .05). We observed decreased 18F‐FDG uptake in several areas, including the temporal lobe (BA22), thalamus, putamen, and cingulate gyrus (BA24), whereas it was increased in the supplementary motor area, postcentral gyrus, lingual gyrus, and precuneus (p < .05). SORs of 11C‐CFT in the bilateral caudate nucleus and ipsilateral posterior putamen were significantly decreased compared to preoperative levels (p < .05).Conclusion: Our findings suggest that STN‐DBS surgery modifies the metabolic network of PD patients and improves motor symptoms, depression, and quality of life. However, it does not prevent the decrease of DAT in striatal areas.
Telehealth use and perceptions among prostate cancer survivors
Authors: Chen Luke W. , Usinger Deborah S. , Katz Aaron J. 
Published: July 2023

AbstractBackgroundReasons underlying disparities in telehealth use among cancer survivors are unknown.MethodsWe surveyed a sociodemographically diverse population‐based cohort of 487 prostate cancer survivors regarding their use and perceptions of telehealth during the COVID‐19 pandemic.ResultsOverall, only 28.5% of survivors had used telehealth at the time of survey and just 10% felt care through telehealth is comparable to that of an in‐person visit. Still, over 55% felt telehealth is a good option for initial consultations or basic care and 15% felt more likely to use telehealth since the pandemic. After adjusting for other socioeconomic factors, survivors with lower education (≤high school vs. any college) had marginally lower use of telehealth (risk ratio [RR], 0.65 [95% CI, 0.42–1.01]) and lower probability of feeling more likely to use telehealth since the pandemic (RR, 0.39 [95% CI, 0.20–0.77]).ConclusionsDifferences in survivor perceptions of telehealth by education level highlight new insights underlying disparities in telehealth use and potential targets for interventions.
Micro‐histology combined with cytology improves the diagnostic accuracy of endometrial lesions
Authors: Wang Yiran , Zhao Lanbo , Zhang Kailu , Liu Yu , Guo Lin , Jing Wei , Hou Huilian , Shi Guizhi , Bin Yadi , Zhang Siyi , Zhang Guanjun , Li Qiling 
Published: July 2023

AbstractBackgroundIn the study, we aimed to evaluate the ability of micro‐histology combined with cytology to improve the quality of slides and diagnose endometrial lesions.MethodsEndometrial specimens were collected from Li Brushes. Every specimen was prepared for micro‐histological and cytological slides, using cell block (CB) and liquid‐based cytology (LBC) technologies. Semi‐quantitative scoring system was used to evaluate the qualities of slides. CB slides were assessed by 5‐category scoring system. Diagnostic accuracy was calculated in LBC, CB, and LBC + CB groups based on the histological gold standard. Endometrial atypical hyperplasia, and endometrial cancer were considered positive, whereas others were considered negative.ResultsA total of 167 patients were enrolled. CB slides were inferior to LBC slides only in cellularity (p < 0.001), but superior in the other six parameters (allp < 0.001). The satisfaction rate of micro‐histology accounted for 92.3%. The accuracy index in the CB group was higher than in the LBC group in terms of sensitivity (85.5% vs. 82.7%) and specificity (98.9% vs. 95.7%). The sensitivity and specificity in the LBC + CB group were increased to 94.2% and 99.0%, respectively.ConclusionsThe quality of micro‐histological slides was higher than that of cytological slides. By combining micro‐histology with cytology, higher accuracy was achieved for endometrial lesions diagnosis.
Association between serum uric acid and prostate cancer mortality in androgen deprivation therapy: A population‐based cohort study
Authors: Lee Yan Hiu Athena , Chan Jeffrey Shi Kai , Leung Chi Ho , Hui Jeremy Man Ho , Dee Edward Christopher , Ng Kenrick , Liu Kang , Liu Tong , Tse Gary , Ng Chi Fai 
Published: July 2023

AbstractObjectiveThis population‐based study examined the association between baseline uric acid (UA) and prostate cancer (PCa)‐related mortality amongst PCa patients receiving androgen deprivation therapy (ADT).MethodsAdults with PCa who received ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with missing baseline UA were excluded. Patients were followed up until September 2021. The outcome was PCa‐related mortality.ResultsAltogether, 4126 patients (median follow‐up 3.1[interquartile range 1.4–6.0] years) were included. A J‐shaped association was observed between baseline UA level and PCa‐related mortality risk, with a direct association in those with mean(0.401 mmol/L) or above‐mean baseline UA levels (hazard ratio (HR) per standard deviation‐increase 1.35 [95% confidence interval 1.21,1.51], p < 0.001), and an inverse association in those with below‐mean baseline UA levels (HR 0.78[0.67,0.92], p = 0.003). The former remained significant on competing risk regression, but not the latter.ConclusionsA J‐shaped relationship between baseline UA level and PCa‐related mortality risk was identified. This study was mainly limited by potential unmeasured and residual confounders. Further validation studies are warranted.
The relational 3C model for research supervision for counsellors, psychotherapists and counselling psychologists
Authors: Bager‐Charleson Sofie , McBeath Alistair , Challenor Julianna 
Published: July 2023

AbstractResearch supervision remains an undertheorised, under‐regulated and often unsupported profession. This article focuses on what research supervisors and research supervisees regard as “helpful” supervision on doctoral programmes in the field of counselling, psychotherapy and counselling psychology. The paper is based on a mixed methods study consisting of an online survey (N = 226) with closed and open questions and optional interviews (10) analysed by “artfully interpretive reflexive thematic analysis” (Supporting research in counselling and psychotherapy qualitative, quantitative, and mixed methods research 19–38. Palgrave Macmillan.). In the survey questions, respondents rated “research knowledge” and “empathy” almost equally. The free‐text comments and interview data added, in turn, deeper and more nuanced understandings into what both research “knowledge” and “empathy” might involve for different people—and at different stages of the research process. The analysis of free‐text comments and interviews moved iteratively back and forth across six stages, typical for reflexive thematic analysis, and was influenced by our interests into “narrative knowing.” We started with the free‐text comments and then read the interviews—to return to our free‐text comment themes from new angles, which eventually were shared in a focus group with supervisors in training. The paper describes the development of a suggested “relational 3C model” with clarity, containment and compassion as key supervisory dimensions applied across eight areas with actions from supervisory contracts to research completion.
Design, Synthesis, and Biological Evaluation of Novel Indanone Derivatives as Cholinesterase Inhibitors for Potential Use in Alzheimer's Disease
Authors: Etemadi Aysan , Hemmati Salar , Shahrivar‐Gargari Mohammad , Abibiglue Yasaman Tamaddon , Bavili Ahad , Hamzeh‐Mivehroud Maryam , Dastmalchi Siavoush 
Published: July 2023

AbstractIndanone derivatives containing meta/para‐substituted aminopropoxy benzyl/benzylidene moieties were designed based on the structures of donepezil and ebselen analogs as the cholinesterase inhibitors. The designed compounds were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were measured. Inhibitory potencies (IC50 values) for the synthesized compounds ranged from 0.12 to 11.92 μM and 0.04 to 24.36 μM against AChE and BChE, respectively. Compound 5 c showed the highest AChE inhibitory potency with IC50 value of 0.12 μM, whereas the highest BChE inhibition was achieved by structure 7 b (IC50=0.04 μM). Structure‐activity relationship (SAR) analysis revealed that there is no significant difference between meta and para‐substituted derivatives in AChE and BChE inhibition. However, the most potent AChE inhibitor 5 c belongs to meta‐substituted compounds, while the most active BChE inhibitor is para‐substituted derivative 7 b. The order of enzyme inhibition potency based on the substituted amine group is dimethyl amine>piperidine>morpholine. Compounds containing C=C linkage are more potent AChE inhibitors than the corresponding saturated structures. Molecular docking studies indicated that 5 c interacts with AChE in a very similar way to that observed experimentally for donepezil. The introduced indanone‐aminopropoxy benzylidenes could be used in drug‐discovery against Alzheimer's disease.
Engineering a Formate Dehydrogenase for NADPH Regeneration**
Authors: Ma Wei , Geng Qiang , Chen Cheng , Zheng Yu‐Cong , Yu Hui‐Lei , Xu Jian‐He 
Published: July 2023

AbstractNicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) constitute major hydrogen donors for oxidative/reductive bio‐transformations. NAD(P)H regeneration systems coupled with formate dehydrogenases (FDHs) represent a dreamful method. However, most of the native FDHs are NAD+‐dependent and suffer from insufficient reactivity compared to other enzymatic tools, such as glucose dehydrogenase. An efficient and competitive NADP+‐utilizing FDH necessitates the availability and robustness of NADPH regeneration systems. Herein, we report the engineering of a new FDH from Candida dubliniensis (CdFDH), which showed no strict NAD+ preference by a structure‐guided rational/semi‐rational design. A combinatorial mutant CdFDH‐M4 (D197Q/Y198R/Q199N/A372S/K371T/▵Q375/K167R/H16L/K159R) exhibited 75‐fold intensification of catalytic efficiency (kcat/Km). Moreover, CdFDH‐M4 has been successfully employed in diverse asymmetric oxidative/reductive processes with cofactor total turnover numbers (TTNs) ranging from 135 to 986, making it potentially useful for NADPH‐required biocatalytic transformations.
Bifunctional Activation of NHC‐Zinc Pre‐Catalyst for Effective Hydroboration of Quinolines and Nitriles
Authors: Ataie Saeed , Baker R. Tom 
Published: July 2023

AbstractZinc dihydride complexes supported by bulky N‐heterocyclic carbenes (NHC) are efficient catalysts in hydroboration reactions. Herein, a set of zinc complexes with an amino‐pyrrolide chelate (HL1) and the small NHC ligand, 2,3‐dimethyl‐3,4‐dichloroimidazol‐2‐ylidene (DDI) was synthesized and characterized. In particular, Zn(HL1)2(DDI) (Zn4) displayed high activity in catalytic nitrile dihydroboration using 0.01 mol % loading, and quinoline hydroboration using 0.05 mol % loading at room temperature. Stoichiometric reaction of Zn4 with 4 equiv. of pinacolborane (HBpin) produced ZnH2(DDI) (Zn5) and 2 equiv. of dissociated (Bpin)2L1. Complex Zn5, generated in situ by this bifunctional catalyst activation step, was shown to be more active than the bis‐NHC analog ZnH2(DDI)2 and previously reported examples with bulky NHC ligands. In addition, variable time normalization analysis (VTNA) showed first‐order dependence on [quinoline], [HBpin] and [Zn4], revealing that a single Zn−H is involved in the catalytic cycle, as was also observed in the stoichiometric reaction of Zn5 with quinoline. VTNA also indicated that this catalyst faces neither deactivation nor product inhibition.