bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro recovery of FIX clotting activity as a marker of highly functional hepatocytes in a hemophilia B iPSC model
Authors: Luce Eléanor , Steichen Clara , Allouche Mickaël , Messina Antonietta , Heslan Jean‐Marie , Lambert Thierry , Weber Anne , Nguyen Tuan Huy , Christophe Olivier , Dubart‐Kupperschmitt Anne 
Published: October 2021

Abstract

Background and Aims
Pluripotent stem cell–derived hepatocytes differentiated in monolayer culture are known to have more fetal than adult hepatocyte characteristics. If numerous studies tend to show that this immature phenotype might not necessarily be an obstacle to their use in transplantation, other applications such as drug screening, toxicological studies, or bioartificial livers are reliant on hepatocyte functionality and require full differentiation of hepatocytes. New technologies have been used to improve the differentiation process in recent years, usually evaluated by measuring the albumin production and CYP450 activity. Here we used the complex production and most importantly the activity of the coagulation factor IX (FIX) produced by mature hepatocytes to assess the differentiation of hemophilia B (HB) patient’s induced pluripotent stem cells (iPSCs) in both monolayer culture and organoids.

Approach and Results
Indeed, HB is an X‐linked monogenic disease due to an impaired activity of FIX synthesized by hepatocytes in the liver. We have developed an in vitro model of HB hepatocytes using iPSCs generated from fibroblasts of a severe HB patient. We used CRISPR/Cas9 technology to target the genomic insertion of a coagulation factor 9 minigene bearing the Padua mutation to enhance FIX activity. Noncorrected and corrected iPSCs were differentiated into hepatocytes under both two‐dimensional and three‐dimensional differentiation protocols and deciphered the production of active FIX in vitro. Finally, we assessed the therapeutic efficacy of this approach in vivo using a mouse model of HB.

Conclusions
Functional FIX, whose post‐translational modifications only occur in fully mature hepatocytes, was only produced in corrected iPSCs differentiated in organoids. Immunohistochemistry analyses of mouse livers indicated a good cell engraftment, and the FIX activity detected in the plasma of transplanted animals confirmed rescue of the bleeding phenotype.
Proteomics analysis reveals digestion‐resistant proteins from colostrum are associated with inflammatory and cytotoxic responses in intestinal epithelial cells
Authors: Chen Yimin , Kim Bum Jin , Dallas David C. 
Published: October 2021

AbstractBackgroundAlthough human‐milk feeding reduces the risk of necrotizing enterocolitis (NEC) in preterm infants compared with formula feeding, the exact risk‐reduction mechanism remains unknown. As NEC occurs at the distal small intestine in which digestion has occurred, we applied proteomics to examine the extent to which colostrum proteins survive simulated infant in vitro–digestion and, thus, have potential to exert biological function.MethodsTen preterm colostrum samples were left undigested or in vitro–digested, and lipopolysaccharide (LPS)‐binding protein, soluble cluster of differentiation 14, and tumor necrosis factor (TNF) receptors I and II were measured using enzyme‐linked immunosorbent assay in all undigested and in vitro–digested samples. Fully differentiated Caco‐2 cells were exposed to digested colostrum samples before stimulation with LPS or TNF or no stimulation. Inflammation (interleukin‐8) and cytotoxicity (lactate dehydrogenase) were measured. Proteomic analyses of undigested and in vitro–digested samples were done using mass spectrometry.ResultsWe found that most proteins in colostrum are significantly, if not completely, degraded after in vitro–digestion. We found select individual and combination digestion‐resistant proteins that were positively correlated with LPS‐ and TNF‐induced inflammation.ConclusionThese results indicate the importance of considering the extent to which specific dietary compounds survive digestion to reach their site of claimed action (distal intestine) and that some digestion‐resistant proteins may be contributing toward “low‐grade” inflammation that is necessary to promote intestinal growth and maturation during early infancy. This work provides the most detailed understanding of human‐milk protein degradation with simulated infant in vitro–digestion to date.
A Novel Adenoidectomy Training System
Authors: Molin Nicole , Wang Nigel , Isaacson Glenn 
Published: October 2021

Objectives/HypothesisYoung residents find mirror‐guided adenoidectomy difficult. Inexperienced trainees must learn to focus a headlight beam, work upside‐down and backward in a small space and thoroughly ablate adenoid tissue—all new skills. We present an adenoidectomy training system that is low‐cost, easy to construct, and is focused on these basic adenoidectomy skills.Study DesignProspective experimental study.MethodsThis training suite includes three stations each targeting a different skill. The first employs a mannequin head with exposed nasopharynx. It trains the student to coordinate a headlight and mirror while touching a series of targets with a curved probe. At the second station participants electrodessicate (or microdebride) an anchored piece of veal thymus. The third station combines both sets of skills as participants ablate thymus in a simulated nasopharynx (30 mm rectangular aluminum tube) constrained within a Crow‐Davis retractor, using a headlight, mirror, and suction electrosurgical electrode (or microdebrider). To evaluate the training system's efficacy, we assessed the performance of 10 surgically naïve medical student volunteers before and after 15 minutes of practice using a validated rating scale used for adenoidectomy.ResultsThere was significant improvement in adenoidectomy skill scores after practicing. Overall scores were higher, time taken to touch a series of targets with a headlight and mirror was less and amount of tissue ablated at the final station was greater (P < .05).ConclusionThis novel adenoidectomy training system is inexpensive and easy to build. Practice with the model resulted in statistically significant improvement in adenoidectomy skill scores for inexperienced student surgeons.Level of Evidence3 Laryngoscope, 132:2056–2062, 2022
Use of antidepressants and risk of repeat self‐harm in older adults 75+ with nonfatal self‐harm: A 1‐year prospective national study
Authors: Hedna Khedidja , Montuori Chiara , Forte Alberto , Pompili Maurizio , Waern Margda 
Published: October 2021

AbstractPurposeTo assess exposure to antidepressants (AD) before and after nonfatal self‐harm (SH) in older adults and to examine 1‐year rates and risk factors for subsequent SH.MethodsLongitudinal national register‐based retrospective cohort study of Swedish residents aged 75+ (N = 2775) with treatment at hospital or specialist outpatient clinic in connection with SH between January 1, 2006, and December 31, 2013. The cohort was followed for 1 year after the index episode. Exposure to AD was assessed at index and at subsequent SH. Cox regression analysis was used to assess factors associated with 1‐year repeat SH.ResultsAt the index episode, 51% were prevalent AD users; 23% started AD during the following year. Overall 12% of prevalent AD users, 8% of AD nonusers, and 6% of AD new users repeated SH or died by suicide. About two‐thirds of these subsequent behaviors occurred within 3 months after the index episode. Men had increased risk of subsequent SH (Hazard ratio [HR] 1.38, 95% CI: 1.09–1.74); older age (>85 years) was associated with a lower risk (HR 0.72, CI 95% 0.55–0.93). Users of AD did not have an increased risk of repeat SH.ConclusionsHalf of older adults who self‐harmed were prevalent AD users and a further one fourth started an AD within 1 year after the index SH. Antidepressant use was not associated with increased risk of subsequent SH in this high‐risk cohort of older adults.
Soil phosphomonoesters in large molecular weight material comprise multiple components
Authors: McLaren Timothy I. , Verel René , Frossard Emmanuel 
Published: October 2021

AbstractThe majority of soil organic P is typically that of “unresolved” phosphomonoesters, which are associated with organic P (Po) in large molecular weight (MW) fractions. However, the composition of this pool of Po remains unclear and could contain more than one component. Our aim was to identify the number and nature of components in soil extracts of different MW using solution 31P nuclear magnetic resonance (NMR) spectroscopy and spectral deconvolution fitting. Three surface soils were collected from native sites, which were extracted for Po using 0.25 M NaOH + 0.05 M Na2–EDTA (unfractionated), followed by size separation using ultrafiltration, resulting in four MW fractions (>10 kDa, <10 kDa, <10 kDa and >3 kDa, and <3 kDa). The NMR analyses revealed a diversity of Po species in all MW fractions across the three soils. In particular, the phosphomonoester region of the >10‐kDa fraction comprised up to 10 components of varying linewidth (0.5–18.6 Hz) and a broad signal (228 Hz). This broad signal was also present in the <3‐kDa fraction, albeit at a lower concentration (average was 29% of that in the unfractionated extracts). Furthermore, solution 31P NMR spectra on the <3‐kDa fraction revealed a diversity of sharp signals (up to 28) in the phosphomonoester region. Overall, our findings show that soil phosphomonoesters in large MW fractions comprise multiple components of varying linewidth.
Potential of Hibiscus sabdariffa Linn. in managing FGF21 resistance in diet‐induced‐obesity rats via miR‐34a regulation
Authors: Kartinah Neng Tine , Komara Nisa , Noviati Nuraini Diah , Dewi Syarifah , Yolanda Sophie , Radhina Afifa , Heriyanto Heriyanto , Sianipar Imelda Rosalyn 
Published: October 2021

AbstractBackgroundObesity is a cause of FGF21 resistance, which affects the browning and thermogenesis process of the adipose tissue. Decreased receptor expression is influenced by miR‐34a, whose expression is increased in obesity. While FGF21‐based therapies have been widely investigated, the potential activity of Hibiscus sabdariffa Linn. extract (HSE) against FGF21 resistance is unknown.ObjectiveThis study aims to determine the effects of HSE on the expression of miR‐34a and FGF21 receptors in white adipose tissue.MethodsThis experimental study used 24 male Sprague‐Dawley rats and divided into four groups: Control (N); diet‐induced‐obesity rats (DIO); DIO rats with HSE 200 mg/kgBW/day and DIO rats with HSE 400 mg/kgBW/day. Rats were fed a high‐fat diet for 17 weeks. HSE was administered daily for 5 weeks. The administration of HSE 400 mg/kgBW/day resulted in the equivalent expression of miR‐34a to that of the control (p > 0.05).ResultsFGFR1 receptor expression was also similar to controls (p > 0.05). Beta‐klotho expression was significantly lower than that of control (p < 0.05) but equivalent to that of DIO rats (p < 0.05).ConclusionsH. sabdariffa has the potential to reduce FGF21 resistance in DIO rats through the suppression of miR‐34a expression and an increase in the number of FGFR1 and beta‐klotho receptors in adipose tissue.
How to Do a Review of the Literature?
Authors: Nundy Samiran , Kakar Atul , Bhutta Zulfiqar A. 
Published: October 2021

AbstractIn scientific writing, whether it is a research paper, thesis, or dissertation, it is important to investigate a problem that has not been tackled before—that is, to fill a gap in the current knowledge. The first question an editor or reviewer asks after seeing a submission is ‘Why did the authors do the work, is the subject original?’
How to Write the Discussion?
Authors: Nundy Samiran , Kakar Atul , Bhutta Zulfiqar A. 
Published: October 2021

AbstractMany authors, and editors, think this is the most difficult part of a paper to write well and have described it variously to be the ‘narrating the story of your research’, ‘the movie or the main scientific script’ and the ‘proof of the pudding’. The idea of a discussion is to communicate to the readers the importance of your observations and the results of all your hard work. In this section, you are expected to infer their meaning and explain the importance of your results and finally provide specific suggestions for future research [1, 2]. The discussion places the outcome into a larger context and mentions the implications of the inferences for theoretical and practical purposes [3].
How to Do a Peer Review?
Authors: Nundy Samiran , Kakar Atul , Bhutta Zulfiqar A. 
Published: October 2021

AbstractPeer review is a process in which a paper’s validity, originality and academic content are checked prior to publication in a good journal. In other words, it is ‘evaluation of work by one or more people with similar competencies’. The people who carry out this work are called reviewers or referees [1].
How to Handle Rejection?
Authors: Nundy Samiran , Kakar Atul , Bhutta Zulfiqar A. 
Published: October 2021

AbstractThe most important reason for immediate rejection is that the authors have not complied with all the necessary requirements of the journal. The submission of auxiliary documents that are necessary (ethics, conflict of interest) may have not been sent. The Editor in charge first looks at the title and the topic of the research [1, 2]. When he feels that it may not have much interest to his readers, the paper can be directly sent back at this level.
How to Conduct a Journal Club?
Authors: Nundy Samiran , Kakar Atul , Bhutta Zulfiqar A. 
Published: October 2021

AbstractReading journals usually starts when you are a postgraduate and a journal club forms an important part of your curriculum. A journal club is a meeting that should be attended by all faculty and trainees. Your mentor will decide which journal articles you should get ready to present and discuss.
The Status of Biomedical Research in Some Developing Countries
Authors: Nundy Samiran , Kakar Atul , Bhutta Zulfiqar A. 
Published: October 2021

AbstractThe International Monetary Fund (IMF) and the United Nations (UN) have both defined developing nations but depend on the country itself to declare whether or not it is still not developed. The Human Development Index (HDI) is easier to understand and is a comparative measure of four parameters—life expectancy, literacy, education, and standards of living for regions worldwide. Countries fall into four broad categories based on their HDI: very high (for developed countries), high and medium (for developing countries), and low (for least developed countries). Alternative classification exists based on the Gross Domestic Product which can classify countries into high- medium-, and low-income group. In this article however, will used the HDI criteria of 2019 for our discussion [1].
Emissionshandel als Leitinstrument für eine effektive und effiziente EU-Klimapolitik im Verkehr
Authors: Eisenkopf Alexander , Knorr Andreas 
Published: October 2021

ZusammenfassungDas oberste klimapolitische Ziel der EU ist die vollständige Dekarbonisierung der Wirtschaft ihrer Mitgliedsstaaten bis 2050, d. h. die Klimaneutralität in allen Sektoren, die derzeit noch von fossilen Brennstoffen abhängig sind. Dies spiegelt sich in der politischen Agenda der EU-Kommission unter dem Titel „European Green Deal“ wider. Um die Klimaneutralität bis 2050 zu erreichen, wurde das bisherige CO2-Zwischenziel der EU kürzlich von 40 % auf 55 % Reduktion bis 2030 verschärft. Im unlängst angekündigten „Fit for 55“-Programm hat die Kommission umfassende Reformen des EU-Emissionshandelssystems, der Erneuerbare-Energien-Richtlinie und der Energiesteuerrichtlinie vorgeschlagen, um den European Green Deal vollständig umzusetzen. Die vorgeschlagenen Maßnahmen werden kritisch bewertet.
Correlation of exercise-induced peripheral venous hypertension with exercise intolerance in patients with Fontan circulation
Authors: Ono Shin , Yanagi Sadamitsu , Wakamiya Takuya , Ichikawa Yasuhiro , Kawai Shun , Kim Ki-Sung , Ueda Hideaki 
Published: October 2021

AbstractOwing to the absence of a sub-pulmonary ventricle, the central venous pressure rises in patients with Fontan circulation. During exercise, central venous pressure may rise further to increase the systemic ventricular preload and cardiac output. We performed a single-centre prospective trial of cardiopulmonary exercise test while monitoring peripheral venous pressure which strongly correlates with central venous pressure. The objective of this study was to test the hypothesis that peripheral venous pressure at peak exercise inversely correlates with exercise capacity in patients with Fontan circulation. Seventeen patients following Fontan operation performed cardiopulmonary exercise test while monitoring peripheral venous pressure. Peak oxygen uptake, heart rate reserve, peak oxygen pulse (divided by body surface area), and peripheral venous pressure at peak exercise were measured. Correlations of peripheral venous pressure at peak exercise with the peak oxygen uptake, heart rate reserve, and peak oxygen pulse were evaluated. The peripheral venous pressure at peak exercise inversely correlated with the peak oxygen uptake (R = −0.66, p < 0.01), heart rate reserve (R = −0.6, p < 0.05), and peak oxygen pulse (R = −0.48, p < 0.05). Exercise-induced peripheral venous hypertension correlates with exercise intolerance in patients with Fontan circulation. Peak oxygen uptake is a useful index for evaluating the status of congestion in the daily life of patients with Fontan circulation.
Reversible Corneal Decompensation Caused by a Topical Dorzolamide/Timolol Fixed Combination After Descemet Stripping Automated Endothelial Keratoplasty
Authors: Kwak Jeeyoung , Jun Jong Hwa 
Published: October 2021

Purpose:
The purpose of this study was to report a case of acute corneal endothelial decompensation caused by a topical dorzolamide/timolol fixed combination (DTFC) after Descemet stripping automated endothelial keratoplasty.

Methods:
A 75-year-old woman who was referred to our hospital with a chief complaint of visual disturbance in the right eye after cataract surgery. Anterior segment optical coherence tomography identified an extensive defect in Descemet membrane. The patient subsequently underwent uneventful Descemet stripping automated endothelial keratoplasty surgery for persistent corneal edema. Two weeks after surgery, she had been prescribed topical DTFC twice daily to control elevated intraocular pressure. On the day she started using the eye drops, the patient noticed an acute deterioration of visual acuity. Severe corneal edema was detected at follow-up 5 days later.

Results:
The topical DTFC was stopped immediately. Thereafter, the corneal edema improved gradually, and there was a reduction in corneal thickness.

Conclusions:
Topical DTFC should be used with caution after corneal endothelial transplantation because of the possibility of iatrogenic corneal endothelial dysfunction.
The Mask-Wearing Bias In The Estimates Of Vaccine Efficacy
Authors: Matytsin Andrew 
Published: October 2021

AbstractIn the United States mask wearing is positively correlated with vaccine acceptance. This correlation introduces an important bias into real-world estimates of vaccine efficacy. I derive the formulae for vaccine efficacy that correct for this phenomenon and show that such biases explain some of the differences between higher estimates of vaccine efficacy observed in the US studies, on one hand, and lower estimates from Israel and Pfizer trials, on the other hand. Control for such biases is important for currently-debated public health decisions regarding COVID19 vaccine booster doses.
Nanoviricides Platform Technology based NV-387 polymer Protects Remdesivir from Plasma-Mediated Catabolism in vitro: Importance of its increased lifetime for in vivo action
Authors: Chakraborty Ashok , Diwan Anil , Arora Vinod , Thakur Yogesh , Holkar Preetam , Chinige Vijetha 
Published: October 2021

AbstractAs of today seven coronaviruses were identified to infect humans, out of which only 4 of them belongs to beta family of coronavirus, like HCoV-HKU1, SARS-CoV-2, MERS-CoV and SARS-CoV. SARS family of viruses were known to cause severe respiratory disease in humans. SARS-CoV-2 infection causes pandemic COVID-19 disease with high morbidity and mortality. Remdesivir (RDV) is the only antiviral drug so far approved for Covid-19 therapy by FDA. However it’s efficacy is limited in vivo due to it’s low stability in presence of Plasma.Here we show the stability of RDV encapsulated with our platform technology based polymer NV-387 (NV-CoV-2-R), in presence of Plasma in vitro in comparison to naked RDV when incubated in plasma. The potential use of this polymer in vivo will be discussed, here.
MutS and DNA Function as a Clamp Loader for the MutL Sliding Clamp During Mismatch Repair
Authors: Yang Xiao-Wen , Han Xiao-Peng , Han Chong , London James , Fishel Richard , Liu Jiaquan 
Published: October 2021

ABSTRACTDNA mismatch repair (MMR) is accomplished by highly conserved MutS and MutL homologs. MutS proteins recognize mismatch nucleotides and in the presence of ATP form a stable sliding clamp on the DNA. The MutS sliding clamp then promotes the cascade assembly of a MutL sliding clamp, which ultimately coordinates downstream mismatch excision. The MutS clamp-loader mechanics are unknown. Here we have examined a conserved positively charged cleft (PCC) located on the MutL N-terminal domain (NTD) proposed to mediate stable DNA binding events in several MMR models. We show that MutL does not bind DNA in physiological ionic conditions. Instead, the MutS sliding clamps and DNA together exploit the PCC to position the MutL NTD for clamp loading. Once in a sliding clamp form, the MutL PCC aids in UvrD helicase capture but not interactions with MutH during mismatch excision. The MutS-DNA clamp-loader progressions are significantly different from the replication clamp-loaders that attach polymerase processivity factors such as β-clamp and PCNA to the DNA. These studies underlining the breadth of mechanisms for stably linking crucial genome maintenance proteins to the DNA.
A study on intention to use social media in higher education: the mediating effect of peer influence
Authors: Trivedi Shrawan Kumar , Patra Pradipta , Singh Saumya 
Published: October 2021

Purpose
Social media sites are one of the vital technological developments of WEB 2.0. This study aims to emphasize on building an empirical model to investigate the impending determinants of users’ intention to use social media sites in higher education. Depending on the existing theories such as the social media acceptance model, e-learning acceptance model, unified theory of acceptance and use of technology and existing literature, determinants such as “performance,” “communication functionality” and “self” have been identified to test. Further, the mediation effect of “peer influence” on the relationship has also been tested.

Design/methodology/approach
A total of 310 students of different private and public Indian institutions have participated in an online survey. Exploratory factor analysis and multiple linear regression analysis are performed and results were analyzed.

Findings
The results of this study demonstrated substantial evidence of the impact of performance, communication functionality and self on the intention to use social media in higher education. The mediation of peer influence has also been seen between all the relations.

Originality/value
An empirical model of intention to use social media in higher education is built. The median of peer influence is tested.