bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclin‐dependent kinase 7 is essential for spermatogenesis by regulating retinoic acid signaling pathways and the STAT3 molecular pathway
Authors: Chen Xu , Li Yan , Dai Haiqian , Zhang Hao , Wan Danyang , Zhou Xinli , Situ Chenghao , Zhu Hui 
Published: October 2021

AbstractSpermatogenesis is a complex process that requires precise regulation. Phosphorylation plays a role in spermatogenesis by regulating protein structure and activity. This study focused on cyclin‐dependent kinase 7 (CDK7), and explored its function and molecular mechanisms in spermatogenesis in vitro in a cell line and in vivo in a mouse model. Inhibition of CDK7 activity affected spermatogonia proliferation and differentiation, and we found that CDK7 regulates retinoic acid (RA)‐mediated c‐KIT expression to play a role in spermatogonia. Then, we demonstrated that inhibition of CDK7 affected meiosis initiation, DNA repair, and synaptonemal complex formation in meiosis progression, and CDK7 played this role by regulating RA‐mediated STRA8 and REC8 signaling pathways. Moreover, inhibition of CDK7 impacted spermatid differentiation and resulted in decreased counts, decreased motility, and increased head deformity of sperm. We demonstrated that CDK7 affects germ cell apoptosis and sperm motility by activating STAT3 and that STAT3 further regulates Cortactin expression to influence the nuclear elongation, chromatin condensation, and acrosome formation of sperm. Additionally, EP300 was identified as another potential target phosphorylated by CDK7 that participates in chromatin condensation. Our results demonstrated the important role of CDK7 in all key aspects of spermatogenesis, potentially providing an effective target for clinical diagnosis and pathogenesis.
Improving ligand‐ranking of AutoDock Vina by changing the empirical parameters
Authors: Pham T. Ngoc Han , Nguyen Trung Hai , Tam Nguyen Minh , Y. Vu Thien , Pham Nhat Truong , Huy Nguyen Truong , Mai Binh Khanh , Tung Nguyen Thanh , Pham Minh Quan , V. Vu Van , Ngo Son Tung 
Published: October 2021

AbstractAutoDock Vina (Vina) achieved a very high docking‐success rate, , but give a rather low correlation coefficient, , for binding affinity with respect to experiments. This low correlation can be an obstacle for ranking of ligand‐binding affinity, which is the main objective of docking simulations. In this context, we evaluated the dependence of Vina R coefficient upon its empirical parameters. is affected more by changing the gauss2 and rotation than other terms. The docking‐success rate is sensitive to the alterations of the gauss1, gauss2, repulsion, and hydrogen bond parameters. Based on our benchmarks, the parameter set1 has been suggested to be the most optimal. The testing study over 800 complexes indicated that the modified Vina provided higher correlation with experiment compared with obtained by the original Vina and by Vina version 1.2. Besides, the modified Vina can be also applied more widely, giving for 32/48 targets, compared with the default package, giving for 31/48 targets. In addition, validation calculations for 1036 complexes obtained from version 2019 of PDBbind refined structures showed that the set1 of parameters gave higher correlation coefficient () than the default package () and Vina version 1.2 (). The version of Vina with set1 of parameters can be downloaded at https://github.com/sontungngo/mvina. The outcomes would enhance the ranking of ligand‐binding affinity using Autodock Vina.
Ultrastructural and physicochemical characterization of pH receptive chlorhexidine‐loaded poly‐L‐glycolic acid‐modified orthodontic adhesive
Authors: Kamran Muhammad Abdullah , Alshahrani Abdulaziz , Alnazeh Abdullah A. , Udeabor Samuel Ebele , Qasim Muhammad , Alshahrani Ibrahim 
Published: October 2021

AbstractThis study aims to evaluate the feasibility of chlorhexidine (CHX)‐loaded poly‐L‐glycolic acid (PLGA) nanoparticles as a modifier of a commercial orthodontic adhesive via the assessment of physicochemical, biological, and mechanical properties at tooth‐bracket interface. CHX‐loaded PLGA nanoparticles were synthesized using double emulsion‐solvent evaporation method and characterized using transmission electron microscopy and Raman analysis. CHX‐loaded PLGA nanoparticles in Transbond XT orthodontic adhesive were prepared using two different concentrations of the CHX (25 and 50%) and characterized for degree of conversion (DC), antimicrobial, and cytotoxicity testing. Bonded specimens were tested for shear bond strength (SBS) and adhesive remnant index (ARI) at tooth‐bracket interface. The synthesized PLGA nanoparticles averaged between 60 and 80 nm in size. After loading CHX inside PLGA nanoparticles, the morphology of the PLGA nanoparticles was considerably changed. Orthodontic bracket bonded with 25% CHX‐loaded PLGA‐modified adhesive demonstrated DC scores similar to control group. Both 25 and 50% CHX‐loaded PLGA‐modified adhesive specimens showed higher antibacterial activity against S. mutans compared to control group. The least mean SBS values were exhibited by 50% CHX‐loaded PLGA‐modified adhesive samples, while a statistically significant difference was observed in the mean ARI values among all study groups at all‐time points (p = .018). This study indicates that the addition of CHX‐loaded PLGA nanoparticles in Transbond XT achieved stable bonds with enhanced antimicrobial and mechanical properties.
Assessing the relationship between patient preferences for recontact after BRCA1 or BRCA2 genetic testing and their monitoring coping style in a Norwegian sample
Authors: Dahle Ommundsen Randi Marlene , Strømsvik Nina , Hamang Anniken 
Published: October 2021

AbstractRecontacting former patients regarding new genetic information is currently not standard care but might be implemented in the future. Little information is available on the implications of this practice from the point of view of former patients. The aim of this study was to investigate preferences for recontact when new genetic information becomes available among patients tested for BRCA pathogenic variants. We further wanted to investigate whether having a high or low information‐seeking coping style (monitoring) impacts preferences. Preferences for recontact were assessed using a self‐constructed questionnaire. The Threatening Medical Situations Inventory (TMSI) was used to measure monitoring coping style. The questionnaires were sent to 500 randomly selected patients who had previously been tested for BRCA pathogenic variants within the time frame 2001–2014 at one genetic clinic in Norway. We received 323 completed questionnaires. Most respondents wanted to be recontacted with advances in genetic medicine (81.1%) and to receive highly personalized updates. Genetic counselors/geneticists were believed to be most responsible for recontact. There was a significant relationship between being a high monitor and wanting recontact to learn about own cancer risk and receive ongoing support. Patients have a high interest in being recontacted. The findings indicated a tendency for high monitors to prefer more detailed and personalized information.
Update on blood‐based biomarkers for chronic liver diseases prognosis: Literature review and institutional experience
Authors: Iwasa Motoh , Shigefuku Ryuta , Eguchi Akiko , Tamai Yasuyuki , Takei Yoshiyuki 
Published: October 2021

AbstractLiver cirrhosis is the final stage of chronic liver disease (CLD) and is associated with high morbidity and mortality. Various complications such as portal hypertension, ascites retention, hepatic encephalopathy, and hepatorenal syndrome deeply affect patient outcome. The most common tools to predict the outcome of a CLD patient include the following: assessing severity of portal hypertension; scoring systems such as the model of end‐stage liver disease and Child–Pugh score and blood biomarkers related to complications and/or survival rate. In this article, we summarize recent studies of noninvasive markers for predicting impending complications related to CLD and discuss the clinical value of currently available blood biomarkers based on evidence from the literature. In addition, noninvasive blood biomarker assays for different prognostic functions were validated on 113 liver cirrhosis patients at our institution using Kaplan–Meier curve analysis to confirm that these markers can satisfactorily predict CLD‐related patient death.
Superiority of clinical American Joint Committee on Cancer T classification for perihilar cholangiocarcinoma
Authors: Yamada Mihoko , Mizuno Takashi , Yamaguchi Junpei , Yokoyama Yukihiro , Igami Tsuyoshi , Onoe Shunsuke , Watanabe Nobuyuki , Uehara Kay , Matsuo Keitaro , Ebata Tomoki 
Published: October 2021

AbstractBackgroundClinical tumor staging is essential information for making a therapeutic decision in cancer. This study aimed to identify the optimal tumor classification system for predicting resectability and survival probability in perihilar cholangiocarcinoma.MethodsPatients who were treated for perihilar cholangiocarcinoma between 2009 and 2018 were enrolled. Local tumor extension was staged radiologically according to a diameter‐based classification system in addition to the AJCC, Blumgart, and Bismuth systems. Survival and resectability were compared between T subgroups, and the discriminability of the four systems was assessed with Harrell’s concordance index (C‐index).ResultsAmong 702 study patients, 559 (80.0%) underwent laparotomy, 489 (70.0%) of whom underwent resection. The resectability significantly decreased for more advanced tumors in all systems (P < .001); the AJCC system had the greatest discriminability for resectability (area under the curve 0.721). Overall survival at 5 years was 69.9% for AJCC cT1, 45.8% for cT2, 31.8% for cT3, and 15.3% for cT4 tumors (cT1 vs cT2; P = .002, cT2 vs cT3; P = .008 and cT3 vs cT4; P < .001). The AJCC system had the largest C‐index of 0.627.ConclusionsThe AJCC T system was the optimal classification system for predicting resectability and survival in perihilar cholangiocarcinoma.
Utility of pyrrole‐2‐thioacetohydrazide in synthesis of new heterocyclic compounds with promising antimicrobial activities and molecular docking studies
Authors: Elsayed Ahmed M. , El‐Remaily Mahmoud Abd El Aleem Ali Ali , Salama Kaoud S. M. , Abdelhamid Antar A. 
Published: October 2021

AbstractOne‐pot synthetic method for [(3‐cyano‐5‐phenyl‐1H‐pyrrol‐2‐yl)sulfanyl]acetic acids 3a,b with excellent yield have been accomplished via a tetrabutylammonium bromide (TBAB) catalyzed reaction of mercaptoacetic acid with 2‐(2‐oxo‐2‐arylethyl) malononitrile under phase transfer catalysis conditions (PTC). The coupling of methyl [(3‐cyano‐5‐phenyl‐1H‐pyrrol‐2‐yl)sulfanyl] acetate 4a,b with hydrazine gave the corresponding 2‐[(3‐cyano‐5‐aryl‐1H‐pyrrol‐2yl)thio] acetohydrazides 5a,b, which reacted with glucose, acetylacetone, carbon disulfide, phenyl isothiocyanate, chloroacetyl chloride or benzaldehyde, to afford the compounds 6a,b–11a,b, respectively ranged from satisfactory to excellent yields. In vitro antibacterial and antifungal activities were assessed with good results. Furthermore, molecular docking experiments were done for the most active compounds against the E. coli MurB enzyme in order to determine the mechanism of their antibacterial activity and showed good binding interactions.
ABCD1 and X‐linked adrenoleukodystrophy: A disease with a markedly variable phenotype showing conserved neurobiology in animal models
Authors: Manor Joshua , Chung Hyunglok , Bhagwat Pranjali K. , Wangler Michael F. 
Published: October 2021

AbstractX‐linked adrenoleukodystrophy (X‐ALD) is a phenotypically heterogeneous disorder involving defective peroxisomal β‐oxidation of very long‐chain fatty acids (VLCFAs), due to mutation in the ABCD1 gene. X‐ALD is the most common peroxisomal inborn error of metabolism and confers a high degree of morbidity and mortality. Remarkably, a subset of patients exhibit a cerebral form with inflammatory invasion of the central nervous system and extensive demyelination, while in others only dying‐back axonopathy or even isolated adrenal insufficiency is seen, without genotype–phenotype correlation. X‐ALD's biochemical signature is marked elevation of VLCFAs in blood, a finding that has been utilized for massive newborn screening for early diagnosis. Investigational gene therapy approaches hold promises for improved outcomes. However, the pathophysiological mechanisms of the disease remain poorly understood, limiting investigation of targeted therapeutic options. Animal models for the disease recapitulate the biochemical signature of VLCFA accumulation and demonstrate mitochondrially generated reactive oxygen species, oxidative damage, increased glial death, and axonal damage. Most strikingly, however, cerebral invasion of leukocytes and demyelination were not observed in any animal model for X‐ALD, reflecting upon pathological processes that are yet to be discovered. This review summarizes the current disease models in animals, the lessons learned from these models, and the gaps that remained to be filled in order to assist in therapeutic investigations for ALD.
Influence of Okhotsk Sea blocking on summer precipitation over South Korea
Authors: Song Chan‐Yeong , Ahn Joong‐Bae 
Published: October 2021

AbstractThis study examined the influence of atmospheric blocking on the variability of precipitation over South Korea during summer (June–July–August) by defining the blocking frequency over the Okhotsk Sea (Okhotsk Sea blocking frequency; OK_BF). According to composite analysis for the years of high precipitation over South Korea, blocking occurs more frequently over the Okhotsk Sea (140°E–160°E). Partial correlation and regression analyses were conducted to separate the contribution of OK_BF to precipitation variability from that of the low‐level meridional wind (LLMW) because LLMW over the region is another important aspect of summer precipitation in South Korea. The barotropic structures of positive geopotential height anomalies over the Okhotsk Sea associated with increasing OK_BF can induce negative temperature anomalies over South Korea due mainly to the equatorward advection of cold air masses from higher latitudes. The enhanced meridional temperature gradient can cause increases in baroclinic instability and zonal wind vertical shear according to the thermal wind balance. This instability can induce anomalous cyclonic circulations over South Korea, resulting in positive precipitation anomalies. The partial correlation coefficients (R2 = 0.35–0.40) between the OK_BF and precipitation indices, including mean precipitation, extreme precipitation intensity, wet days, and consecutive wet days, were all statistically significant at the 95% confidence level. Overall, the effects of the increasing OK_BF on both precipitation and potential evapotranspiration can intensify the surface water budget in South Korea.
Recent variations in the seasonality difference between precipitation and potential evapotranspiration in China
Authors: Ning Tingting , Feng Qi , Qin Yanyan 
Published: October 2021

AbstractThe seasonality difference between precipitation (P) and potential evapotranspiration (E0) has a significant imprint on ecohydrological processes, but little attention has been given to this difference in China. A climate seasonality and asynchrony index (SAI), considering the amplitude and phase difference (PD) between P and E0, was thus applied to investigate the variation in seasonality difference between P and E0 across China from 1960 to 2017. The main results showed that the mean amplitudes of seasonal P (δP) were larger than that of E0 (δE0). Except for in east and central south China, the peak values of E0 had a time lag of 23 days behind those of P. The annual SAI in China showed a significantly downward trend (p <  0.05), suggesting a reduction in the difference in seasonal P and E0 in China. The attribution results showed that the variation in SAI was mainly controlled by δP changes across China with a relative contribution of 60.5%, followed by δE0 (35.9%) and PD (3.6%). Wavelet analysis showed that the annual SAI had a significant relationship with ocean–atmosphere circulation patterns at a scale of 1–6 years (p <  0.05). As an attempt to investigate the difference in seasonal P and E0 in China, the findings of this study can provide a reference for climate seasonality variations and support for the quantification of its effects on the ecohydrological environment.
Influence of environmental growth temperature on tocopherol and sterol oil concentrations in olive fruit
Authors: Hamze Leila , Miserere Andrea , Molina M Sol , Maestri Damian , Searles Peter S , Rousseaux M Cecilia 
Published: October 2021

AbstractBACKGROUNDTocopherols and sterols are minor components of virgin olive oils that contribute to oil quality. Based on observations at different geographical locations, it has been suggested that environmental temperature during fruit growth affects tocopherol and sterol oil concentrations in olive fruit. However, controlled experiments have not been conducted to directly assess their responses to temperature. In this study, a manipulative experiment using open‐top chambers (OTCs) was performed in the field to evaluate the responses of these oil components to a moderate air temperature increase during oil accumulation in young trees of two olive cultivars (Arbequina, Coratina). The two temperature levels in the OTCs were a control about 1 °C above ambient temperature (T0) and a heated treatment (T+) with a target temperature of 4 °C above T0.RESULTSTotal tocopherol and sterol oil concentrations in olive fruit were generally higher in the T+ temperature treatment than in the control at the end of the oil accumulation period. The increase in total tocopherols in T+ appeared to be related to a decrease in fruit oil concentration with heating. Individual sterols showed both significant increases and decreases due to T+, and some differences in response occurred between the two cultivars.CONCLUSIONThese findings provide evidence that growth temperature affects tocopherol and sterol oil concentrations in olive fruit at the end of the oil accumulation period. Cultivars should be carefully chosen for new olive‐growing regions, and the results could be relevant for global warming scenarios in existing growing regions. © 2021 Society of Chemical Industry.
Growth stage and ensiling: impact on chemical composition, conservation quality and in situ ruminal degradability of whole‐crop oat
Authors: Stirling Sofía , Díaz Juan E , Repetto José L , Pla Marcelo , Arroyo José M , Cajarville Cecilia 
Published: October 2021

AbstractBACKGROUNDThe effects of growth stage (GS) and ensiling were assessed on whole‐crop oat's (Avena sativa L. cv. Cantara) chemical composition, silage fermentation quality and in situ ruminal degradability. Oat was harvested and ensiled at six GS: boot, heading, water ripe, early milk, early dough and grain ripe (144, 151, 178, 234, 362 and 512 g kg−1 of dry matter (DM) of whole‐crop forage, respectively).RESULTSGS influenced chemical composition, silage fermentation quality and ruminal degradability of whole‐crop oat. Lower DM and higher water‐soluble carbohydrates (WSC) contents lead to adequate forage compaction and fermentation at early GS; however, effluent was produced until the dough stage (L and Q; P ≤ 0.003). Advancing in maturity increased (P < 0.001) crop yield (4.5 to 9.4 t DM ha−1), DM (144 to 512 g kg−1), neutral detergent fibre (NDF; 537 to 571 g kg−1 DM), lignin (44.6 to 71.3 g kg−1 DM) and starch contents (26.4 to 201 g kg−1 DM), and reduced (P < 0.001) crude protein (107 to 60 g kg−1 DM) and WSC (115 to 17.5 g kg−1 DM). DM and NDF ruminal degradability declined with maturity for fresh and ensiled forages (L and Q; P < 0.05). Density and buffering capacity decreased with GS (L and Q; P < 0.001), whereas pH and soluble protein increased (L and Q; P ≤ 0.004).CONCLUSIONThe growth stage of oat influenced the nutritive value and ruminal degradation to a greater extent than ensiling, and thus it can play a paramount role in whole‐crop oat silage quality. © 2021 Society of Chemical Industry.
Qualitative‐quantitative analysis of multi‐mycotoxin in milk using the high‐performance liquid chromatography‐tandem mass spectrometry coupled with the quick, easy, cheap, effective, rugged and safe method
Authors: Zheng Baohua , Yu Yunhan , Wang Meiling , Wang Jianwu , Xu Huilan 
Published: October 2021

AbstractHigh‐performance liquid chromatography‐tandem mass spectrometry coupled with the quick, easy, cheap, effective, rugged and safe method was established for the qualitative and quantitative detections of 20 mycotoxins in milk. The linear range of this method was 0.01–10 μg/L and the correlation coefficients were all greater than or equal to 0.9933. At three levels of addition, the spiked recoveries ranged from 80.00 to 112.50%, relative standard deviations were 2.67–14.97%, limits of quantitation were 0.02–4.00 μg/kg, and limits of detection were 0.007–1.300 μg/kg. This developed procedure for the identification and quantitation of mycotoxins provided prospective support for quality regulation.
Assessment of thrombocytopenia, sleep apnea, and cardiac involvement in GNE myopathy patients
Authors: Mori‐Yoshimura Madoka , Kimura Ayano , Tsuru Ayumi , Yajima Hiroyuki , Segawa Kazuhiko , Mizuno Katsuhiro , Oya Yasushi , Noguchi Satoru , Nishino Ichizo , Takahashi Yuji 
Published: October 2021

AbstractIntroductionWe previously identified UDP‐N‐acetylglucosamine 2‐epimerase (GNE) myopathy patients with sleep apnea and a past history of thrombocytopenia, but without disease‐specific cardiac involvement. This study aimed to clarify the occurrence, severity, and serial changes of these complications.MethodsThirty‐three genetically confirmed GNE myopathy patients who participated in a 5‐y longitudinal observational history study underwent platelet count and platelet‐associated immunoglobulin G (PA‐IgG) measurements, a sleep study, and electrocardiography (ECG), Holter ECG, and echocardiogram examinations.ResultsAmong the 33 patients, three had low platelet counts and 17 out of 26 were PA‐IgG positive. No patient exhibited bleeding tendencies, and 3 out of 28 had low platelet counts. Muscle weakness was more pronounced, and summed MMT and grip power significantly lower, in PA‐IgG‐positive patients than in PA‐IgG‐negative patients. Of 19 patients, 7, 4, and 3 who underwent a sleep study had mild, moderate, and severe sleep apnea, respectively, and three started continuous positive airway pressure (CPAP). The respiratory disturbance index was not significantly correlated with physical evaluation items or forced vital capacity. All patients underwent ECG, 32 underwent cardiac ultrasound, and 25 underwent Holter ECG. No disease‐specific cardiac involvement was noted, no serial changes during the follow‐up period were observed for ECG and echocardiography, and none of the patients required therapy for cardiac abnormalities.DiscussionPA‐IgG is a potential disease biomarker in GNE myopathy patients, although its significance needs to be clarified. While none of the patients in this study experienced cardiomyopathy or arrythmia due to myopathy, sleep apnea was identified as a frequent complication.