bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teloxantron inhibits the processivity of telomerase with preferential DNA damage on telomeres
Authors: Maciejewska Natalia , Olszewski Mateusz , Jurasz Jakub , Baginski Maciej , Folini Marco , Zaffaroni Nadia 
Published: June 2022

Abstract
Telomerase reactivation is one of the hallmarks of cancer, which plays an important role in cellular immortalization and the development and progression of tumor. Chemical telomerase inhibitors have been shown to trigger replicative senescence and apoptotic cell death both in vitro and in vivo. Due to its upregulation in various cancers, telomerase is considered as a potential target in cancer therapy. In this study, we identified potent, small-molecule telomerase inhibitors using telomerase repeat amplification protocol assay. The results of the assay are the first evidence of telomerase inhibition by anthraquinone derivatives that do not exhibit G-quadruplex-stabilizing properties. The stability of telomerase in the presence of its inhibitor was evaluated under nearly physiological conditions using cellular thermal shift assay. Together with the compound-induced aggregation, human telomerase reverse transcriptase (hTERT) was translocated from the nucleus to the cytoplasm, which suggested compound-mediated inhibition making the enzyme accessible to its natural substrate. Molecular studies confirmed the binding of hit compound with the active site of hTERT. The ability of new derivatives to activate DNA double-strand breaks (DSBs) was determined by high-resolution microscopy and flow cytometry in tumor cell lines differing in telomere elongation mechanism. The compounds triggered DSBs in TERT-positive A549 and H460 cell lines, but not in TERT-negative HUVEC and ALT-positive U2OS cell lines, which indicates that the induction of DSBs was dependent on telomerase inhibition. The observed DNA damages activated DNA damage response pathways involving ATM/Chk2 and ATR/Chk1 cascades. Additionally, the compounds induced apoptotic cell death through extrinsic and intrinsic pathways in nonsmall cell lung cancer cells. Taken together, our study demonstrated that anthraquinone derivatives can be further developed into novel telomerase-related anticancer agents.
Sequence variants affect the genome-wide rate of germline microsatellite mutations
Authors: Kristmundsdottir Snaedis , Jónsson Hákon , Hardarson Marteinn , Pálsson Gunnar , Beyter Doruk , Eggertsson Hannes , Gylfason Arnaldur , Sveinbjornsson Garðar , Holley Guillaume , Stefansson Olafur , Olafsson Sigurgeir , Arnadottir Gudny , Olason Pall , Eiriksson Ogmundur , Masson Gisli , Thorsteinsdottir Unnur , Rafnar Thorunn , Sulem Patrick , Helgason Agnar , Gudbjartsson Daniel , Halldorsson Bjarni , Stefansson Kari 
Published: June 2022

Abstract
Microsatellites are polymorphic tracts of short tandem repeats (STRs) with one to six base-pair (bp) motifs and are some of the most polymorphic markers in the genome. Using 6,084 Icelandic parent-offspring trios we estimate 63.7 (95% CI: 61.9–65.4) microsatellite de novo mutations (mDNMs) per offspring per generation. Paternal mDNMs occur at longer repeats, while maternal mDNMs affect more bp. mDNMs increase by 0.97 (95% CI: 0.90–1.04) and 0.31 (95% CI: 0.25–0.37) per year of father‘s and mother‘s age at conception, respectively. We found two independent coding variants associated with an increased number of mDNMs transmitted to offspring; A missense variant (allele frequency (AF) = 1.9%) in MSH2, a mismatch repair gene, increases transmitted mDNMs from both parents (effect: 13.1 paternal and 7.8 maternal mDNMs). A synonymous variant (AF = 20.3%) in NEIL2, a DNA damage repair gene, increases paternally transmitted mDNMs (effect: 4.4 mDNMs). Thus, the microsatellite mutation rate in humans is in part under genetic control.
Depositional morphotypes and characterization of silica diagenesis in Ypresian-Priabonian gypsiferous carbonates, Gafsa, Southern Tunisia
Authors: Henchiri Mohsen , Zammali Rim , Abid Khawla , Zidi Mohamed Khalil , Ahmed Walid Ben 
Published: June 2022

Abstract
Silica diagenetic features have been recognized in the Ypresian – Priabonian gypsiferous carbonates of Kef Edour Member in Gafsa basin, southern Tunisia. These rocks host a broad range of nodular features including anhydrite / gypsum, nodules and silica geodes. Three types of silica geodes have been recognized based on colour, form, chemical and mineralogical composition. A zoned texture characterizes most of geodes, with (1) a rim, 3­4 cm thick, composed of mixed microquartz and (2) length-slow chalcedony and (3) euhedral Megaquartz lining the inner cavity of the nodule. XRD analysis reveals that the quartz is the only silica phase present in most samples. The other silica forms (opaline group = opal-A, opal-C, opal-CT) are undetectable with XRD. FTIR and 29Si MAS NMR analyses confirm the presence of diagenetic hydroxylated silica forms (silanol sites with two bridging oxygen sites Q2 (–(O)2Si(OH)2) interpreted as amorphous opaline precursors of the quartz. Other non-siliceous groups have been detected, such as SO4 (sulphate evaporites) CO3 (calcium and magnesium carbonates), and confirmed by petrographic observations. In Mg-rich and gypsiferous host sediments, silica diagenesis tends to proceed discontinuously. During early silicification, pore fluid chemistry (pH < 9) tolerates silica replacements and the development of the microcrystalline and fibrous form of quartz, whereas this silica replacement is slowed down or curtailed later in the innermost parts of anhydrite nodules due pore fluid chemistry (pH values > 9) allowing the development of euhedral silica form by force of crystallization supported by its crystallinity degree and its low specific surface area and ultramicroporosity that make it the most mineralogically competent and the most chemically resistant in such environments. Silica supply could be derived ultimately from (1) minor volcanogenic/hydrothermal venting contributions during early diagenetic stages, and (2) diagenesis of the extraformational and overlying detrital quartz and clay-rich sediments.
Caloric and Time Restriction Diets Improve Acute Kidney Injury in Experimental Menopausal Rats: Role of SIRT1 and TGF-β1
Authors: Mahani Fatemeh Darvishzadeh , Khaksari Mohammad , Mousavi Maryam Sadat , Bashiri Hamideh , Raji-Amirhasani Alireza , Hajializadeh Zahra , Alavi Samaneh Sadat 
Published: June 2022

Abstract
BackgroundEstrogen has a protective effect on acute kidney injury (AKI). In addition, reducing daily calorie intake prevents disease. The aim of this study was to determine the effect of calorie restriction (CR) and time restriction (TR) diets on the expression of SIRT1, TGF-β1 and other indicators in the presence or absence of Ovaries in female rats with AKI.MethodsFemale rats were divided into two groups of resected ovaries (OVX) and sham and were subjected to CR and TR diets for eight weeks. AKI was then induced by glycerol injection and renal injury indices and biochemical parameters were measured before and after AKI.ResultsAfter AKI, the levels of urine albumin excretion rate, urea, and creatinine in serum, and TGF-β1 increased, while GFR and SIRT1 decreased in kidney tissue. CR improved kidney indicators and caused a reduction in TGF-β1 and an increase in SIRT1 in ovary-intact rats. Moreover, CR prevented TAC decrease and MDA increase resulting from AKI. Before AKI, an increase in body weight, fasting blood sugar (FBS), LDL, TG, and TC and a decrease in HDL were observed in OVX rats compared to sham rats, but CR prevented these changes. The effects of TR were similar to those of CR in all indicators except for TGF-β1, SIRT1, urea, creatinine, and albumin. ConclusionThis study showed that CR diet is more effective than TR diet in preventing AKI by increasing SIRT1 and reducing TGF-β1 in ovary-intact animals.
The nonlinear impact of R&amp;D investment on green technological progress in China’s manufacturing industry: Based on the law of diminishing marginal returns
Authors: Zhang Xi , Li Rui , Zhang Jinglei 
Published: June 2022

Abstract
Green technological progress is an important prerequisite for the sustainable development of the manufacturing industry, which is usually closely related to R&D investment activities. This paper explores the nonlinear relationship between R&D investment and green technological progress based on panel threshold regression model using panel data of 26 manufacturing industries in China from 2004 to 2017. The results show that the double-threshold model can better explain the nonlinear relationship between the two, and the R&D investment in the three ranges of low, medium and high levels can significantly promote green technological progress in manufacturing industry. However, with the improvement of R&D investment level, the promotion effect of R&D investment on the progress of manufacturing green technology is decreasing, which explains the low R&D intensity of China's manufacturing industry to a certain extent. When the level of R&D investment reaches a certain level, its promoting effect on green technological progress will be greatly reduced, and the motivation of enterprises to invest in R&D based on self-interest will decrease, so that the scale of R&D investment will be lower than the optimal scale of society. R&D investment can also improve green technical efficiency change. In addition, environmental regulation can promote green technological progress in manufacturing industry. However, due to the implementation of output-oriented environmental regulation policies, China’s environmental regulation can inhibit the improvement of green technical efficiency change. Based on the conclusion, this paper argues that China should implement differentiated R&D subsidy policies for manufacturing enterprises, especially to increase R&D subsidies for enterprises with a medium level of R&D investment, and formulate appropriate environmental regulatory policies, so as to promote green and low-carbon transformation of China's manufacturing sector.
The epidemiological and clinical characteristics of COVID-19 in a high HIV/TB burden district level hospital setting
Authors: Mnguni Ayanda Trevor , Schietekat Denzil , Ebrahim Nabilah , Sonday Nawhaal , Boliter Nicholas , Schrueder Neshaad , Gabriels Shiraaz , Sigwadhi Lovemore N. , Zemlin Annalise E. , Chapanduka Zivanai C. , Ngah Vera , Yalew Anteneh , Jalavu Thumeka , Abdullah Ibtisam , Tamuzi Jacques L. , London Leslie , Naledi Tracey , Tembo Yamanya , Davies Mary-Ann , Nyasulu Peter S. , English Rene 
Published: June 2022

Abstract
Background:
The coronavirus disease 2019 (COVID-19) pandemic continues to evolve. Globally, COVID-19 continues to strain even the most resilient healthcare systems, with Omicron being the latest variant. We made a thorough search for literature describing the effects of the COVID-19 in a high human immunodeficiency virus (HIV)/tuberculosis (TB) burden district-level hospital setting. We found scanty literature.
Methods:
A retrospective observational study was conducted at Khayelitsha District Hospital in Cape Town, South Africa (SA) over the period March 2020 – December 2021. We included confirmed COVID-19 cases with HIV infection aged from 18 years and above. Analysis was performed to identify predictors of mortality or hospital discharge among people living with HIV (PLWH). Predictors investigated include CD4 count, antiretroviral therapy (ART), TB, non-communicable diseases, haematological, and biochemical parameters.
Findings:
This cohort of PLWH with SARS-CoV-2 infection had a median (IQR) age of 46 (37–54) years, male sex distribution of 29.1%, and a median (IQR) CD4 count of 267 (141–457) cells/mm3. Of 255 patients, 195 (76%) patients were discharged, 60 (24%) patients died. One hundred and sixty-nine patients (88%) were on ART with 73(28%) patients having acquired immunodeficiency syndrome (AIDS). After multivariate analysis, smoking (risk ratio [RR]: 2.86 (1.75–4.69)), neutrophilia [RR]: 1.024 (1.01–1.03), and glycated haemoglobin A1 (HbA1c) [RR]: 1.01 (1.007–1.01) were associated with mortality.
Conclusion:
The district hospital had a high COVID-19 mortality rate among PLWH. Easy-to-access biomarkers such as CRP, neutrophilia, and HbA1c may play a significant role in informing clinical management to prevent high mortality due to COVID-19 in PLWH at the district-level hospitals.
CD44 mediates hyaluronan to promote the differentiation of human amnionic mesenchymal stem cells into chondrocytes through the activation of Erk1/2 and Smad2 signals
Authors: Xu Yan , Wang Ai-Tong , Xiao jianhui 
Published: June 2022

Abstract
Background: Hyaluronan (HA), as a major component of the cellular matrix, plays an important role in cartilage formation. Our previous studies showed that HA may induce human amnion mesenchymal stem cells (hAMSCs) to differentiate into chondrocytes. The surface molecule CD44, as the main receptor of hyaluronic acid, is crucial for maintaining cartilage homeostasis. But the effect and molecular mechanism of CD44 on HA-induced hAMSCs differentiation into cartilage is unknown. Results: The expression of aggrecan and type II collagen was down-regulated after using the antibody blocker anti-CD44 antibody (A3D8) in HA-induced group. Meanwhile, the transcriptional levels of chondrocyte‑associated genes SRY‑box transcription factor 9 (SOX9), aggrecan (ACAN) and collagen type II alpha 1 chain (COL2A1) were also decreased. Thus CD44 may mediates HA-induced differentiation of hAMSCs into chondrocytes. Further investigation indicated that expression of phosphorylated (p)‑Erk1/2 and p‑Smad2 was decreased following CD44 inhibition. The changes in the expression levels of p-Erk1/2 and p-Smad2 were consistent after treatment with ERK1/2 inhibitor (U0126) and agonist (EGF), respectively. At the same time, after the use of p-Smad2 inhibitor, the expression levels of p-ERK1/2 and p-Smad2 were both down-regulated, and TGF-β, an agonist of p-Smad2, had no effect on the expression of p-ERK1/2, but decreased the expression of p-Smad2. Results showed that there was a cross-talk between Erk1/2 and Smad2. In addition, inhibition of p-Erk1/2 and p-Smad2 can significantly reduce the accumulation of aggrecan and type II collagen.Conclusion: These data indicated that CD44 mediated HA-induced differentiation of hAMSCs into chondrocytes via regulating Erk1/2 and Smad2 Signals.
Proper Understanding of Recurrent Stress Urinary Incontinence Treatment in women (PURSUIT): A Randomised Controlled Trial of Endoscopic and Surgical Treatment
Authors: Clark Lucy , Fitzgerald Beth , Noble Sian , MacNeill Stephanie , Paramasivan Sangeetha , Cotterill Nikki , Hashim Hashim , Jha Swati , Toozs-Hobson Philip , Greenwell Tamsin , Thiruchelvam Nikesh , Agur Wael , White Alison , Garner Victoria , Cobos-Arrivabene Marta , Clement Clare , Cochrane Madeleine , Liu Yumeng , Lewis Amanda L , Taylor Jodi , Lane Athene , Drake Marcus J , Pope Caroline 
Published: June 2022

Abstract
Background: Women with stress urinary incontinence (SUI) experience urine leakage with physical activity. Currently the interventional treatments for SUI are surgical, or endoscopic bulking injection(s). However, these procedures are not always successful, and symptoms can persist or come back after treatment, categorised as recurrent SUI. There are longstanding symptoms and distress associated with a failed primary treatment and currently there is no consensus on how best to treat women with recurrent, or persistent, SUI. Methods: A two-arm trial, set in at least 20 National Health Service (NHS) urology and urogynaecology referral units in the United Kingdom, randomising 250 adult women with recurrent or persistent SUI 1:1 to receive either an endoscopic intervention (endoscopic bulking injections) or a standard NHS surgical intervention, currently colposuspension, autologous fascial sling or artificial urinary sphincter. The aim of the trial is to determine whether surgical treatment is superior to endoscopic bulking injections in terms of symptom severity at 1-year after randomisation. This primary outcome will be measured using the patient-reported International Consultation on Incontinence Questionnaire - Urinary Incontinence - Short Form (ICIQ-UI-SF). Secondary outcomes include assessment of longer-term clinical impact, improvement of symptoms, safety, operative assessments, sexual function, cost-effectiveness and an evaluation of patients’ and clinicians’ views and experiences of the interventions.Discussion: There is a lack of high-quality, randomised, scientific evidence for which treatment is best for women presenting with recurrent SUI. The PURSUIT study will benefit healthcare professionals and patients and provide robust evidence to guide further treatment and improve symptoms and quality of life for women with this condition. Trial registration: International Standard Randomised Controlled Trials Number (ISRCTN) registry, ID: ISRCTN12201059. Registered on 09 January 2020.
Temporal Patterns of Voice Onset Time of English-Sindhi Stops
Authors: Abbasi Abdul Malik , Channa Mansoor Ahmed , Khan Ms Ahlam 
Published: June 2022

Abstract
The paper examines the temporal voice onset time (VOT) duration of consonantal stops between the release burst of stops and the onset of vibration of the voice box. This is an acoustic study of Voice Onset Time of L1 Sindhi and L2 English stops. It aims to determine the acoustic average values of Voice Onset Time (VOT) in Sindhi English stop consonants i.e. L1 and L2 production of speech. According to the author, this descriptive study Voice Onset Time (VOT) in Sindhi-English stop consonants has been conducted first time on English-Sindhi VOT (ms) stops. The study recruited 10 (5 females and 5 male participants), who were Sindhi native speakers and English as a Second Language (ESL) Learners. The stimuli were designed in which three voicing pairs were selected from both Sindhi and English. The VOT (ms) of six Sindhi and English voicing stop pairs /p/, /t/, /k/ & /b/, /d/, and /ɡ/ were measured i.e. one voiceless and one voiced. The undergraduate students recorded their voice samples in both Sindhi and English. The data were separately analyzed from Sindhi and English languages. There were acoustic differences within the groups and between the groups in VOT (ms) of English and Sindhi. The statistical tests were run on the results where the significance level of p-value was fixed on < 0.05. The results illustrate that there is a significant difference between voiceless sounds i.e. /p/ & /k/ means. The findings of the data reveal that there is no statistically significant difference between VOT (ms) means of male & female for the voiceless & voiced consonantal sounds i.e., /t/, /b/, /d/ & /ɡ/. The data further discovered that English-Sindhi VOT characteristics of stops are not associated with gender; however, English-Sindhi VOT altered as a function of the place of articulation.
The importance of integrating Digital Language Learning system in the Listening classroom
Authors: Gobena Gadisa Tadesse 
Published: June 2022

Abstract
Listening comprehension is crucial to language learning for learners. There is no doubt that student who can apply their listening skills enable to their language proficiency on other too. Because of the instructors deeply stay on other language skills, students lag their skills to listening, and decide as it was simple to understand it. However, different supportive strategies to listening skills such Digital Language Learning System installation for EFL students have several lots of purposes as it helps both instructors and students of the language. The application of using Digital Language Learning System helps the students to learn through self-study, demonstration, listening audio materials and develop their language proficiency. The intended uses Digital Language Learning in the English classroom have been considered as the major resource to develop students’ language skills among the students. However, the pedagogy of preparing the lesson plan to teach English listening skills in the daily classroom is nearly neglected one. There is a complacency that having the skills of speaking, writing, and reading in EFL Class able to make us satisfied. To this end, FL English language instructors ignore listening skills since they are not avail themselves in trying to teach this skill in their lesson to make students acquire the target language.
The Effect of Pelvic Floor Rehabilitation on Lower Anterior Resection Syndrome After Colorectal Cancer Treatment
Authors: Jones Shelby , Edie Allison , Hill Joshua S. , Thompson Julie A. , Troop Emily 
Published: June 2022

Abstract
Purpose
Lower anterior resection (LAR) is the preferred surgical treatment of rectosigmoid or rectal cancers but is often associated with bowel dysfunction, termed Lower Anterior Resection Syndrome (LARS). Daily bowel dysfunction symptoms have a detrimental effect on quality of life (QOL). Pelvic floor rehabilitation (PFR) can improve pelvic floor function and QOL among patients with LARS. This quality improvement (QI) project seeks to assess prevalence of LARS within our population and develop and incorporate PFR for treatment and prevention of LARS.
Methods
A convenience sample of 20 patients met project inclusion and 13 participated. Individuals were categorized by diagnostic risk: “low risk”, “high risk”, and “established.” The intervention included 1-hour PFR sessions with the physical therapist (PT) and 5 minutes of daily self-led pelvic floor muscle exercises. Outcome questionnaires included the LARS Score and FiQOL Scale. Data were collected both pre and post CRC treatment.
Results
Overall prevalence of LARS was 76.9% and significantly higher than the retrospective cohort comparison rate of 21.8% (p < .001). Prevalence of major LARS was 89%, 83%, and 50% at initial, second, and third session, representing a 44% relative decrease. Embarrassment was significantly affected among individuals with major LARS, though ongoing PFR facilitated improvement.
Conclusion
PFR is a valuable adjunct therapy for LARS, with continued sessions decreasing overall prevalence among our cohort. Major LARS negatively impacts QOL measures early on in treatment but improves with continued PFR.
Construction method of equipment defect domain ontology
Authors: yang huafei , yang wenqing , Zhang Nan , Wei Shanming , Shang Yingnan 
Published: June 2022

Abstract
Equipment defect domain ontology is the semantic basis for constructing equipment defect knowledge graph, which can be used to organize, share, and analyze equipment defect related knowledge. At present, there are many relevant data in the field of equipment defects, such as equipment information model, equipment management documents, and equipment defect reports. These equipment defect data often focus on a single aspect of the equipment defect field. It is difficult to integrate the database with various types of equipment defect information. This paper combines the characteristics of existing equipment defect data sources to build a general equipment defect domain ontology. This research can break the barrier of multi-source heterogeneous knowledge, build an efficient storage engine for multimodal data, and empower the safety of industrial Internet.