bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Dio2 gene expression by thyroid hormones in normal and type 1 deiodinase-deficient C3H mice
Authors: Wagner Marcia S , Wajner Simone M , Dora José M , Maia Ana Luiza
Published: May 2007

The C3H/HeJ mouse presents an inherited type 1 deiodinase (D1) deficiency that results in elevated serum thyroxine (T4), whereas TSH and tri-iodothyronine (T3) concentrations are normal when compared with those in the C57BL/6J strain. Here, we evaluated the expression of the type 2 (D2), the other T4-activating enzyme, in C3H mice. A comparative analysis revealed that D2 mRNA levels in C3H are similar to those in C57 animals. The D2 activity in C3H pituitary and brain are reduced when compared with those in the C57 strain (3.75 ± 1.08 vs 5.78 ± 0.33 and 0.17 ± 0.05 vs 0.26 ± 0.07 fmol/min per mg protein respectively). However, no differences on D2 activity levels were observed in the brown adipose tissue (BAT) between both strains (0.34 ± 0.06 vs 0.36 ± 0.09 fmol/min per mg protein). Experiments using different T4 doses showed that higher levels of serum T4 than those of the C3H mouse are required to downregulate D2 activity in this tissue. T3 administration to euthyroid mice resulted in a two- to four-fold increase on D2 activity in BAT and brain of both strains, despite a marked decrease in BAT D2 transcripts and no changes in brain D2 mRNA levels. The increase in D2 activity was preceded by a decrease in serum T4 levels, which appears to reduce D2 degradation. Indeed, administration of T3 plus T4 abolished the T3-induced D2 upregulation. In conclusion, our results demonstrated that D2 activity is mainly regulated at posttranslational level in a tissue-specific manner. These observations further characterize and provide insights into the complex and dual regulatory role of the iodothyronines in D2 regulation.
Speed and reloading effects on pavement rutting
Authors: Korkiala-Tanttu L.
Published: May 2007

This paper concentrates on two factors that affect the permanent deformation (rutting) of unbound pavement layers. These factors are the loading speed and stress history. The loading speed has a simultaneous two-way effect: the permanent response of the unbound material itself, and the change in the stress state depending on the resilient properties of the upper-bound layers. The modelled examples show that the dominating factor in the speed effect is the change in stress state due to the change in the resilient properties of the bound layers, whereas the speed effects on the unbound material itself have a smaller role. In addition, the effect of loading speed depends greatly on the temperature, varying from 10–15% at 10°C to 20–25% at 25°C. The measured effects can be estimated reasonably well with modelling. Unloading—reloading cycles at various load levels have little effect on the permanent deformation. The effect is usually so small that it can be neglected in calculations, but the preloading history itself has a clear effect on the permanent deformation.
Development of Hairsine method for design of L-shaped walls
Authors: Justo J. L. , Durand P. , Justo E.
Published: May 2007

Hairsine published a paper in 1972 in the Proceedings of the Institution of Civil Engineers entitled ‘A design chart for determining the optimum base proportions of free standing retaining walls’, which has been used ever since for designing L-shaped walls. For small surcharge pressures, the author provides only an approximate method. Hairsine suggests a complicated procedure when surcharge loading represents a large proportion of the wall loading: if this procedure is used, the method loses its effectiveness. This paper sets out to show how, by introducing simple equivalent coefficients, the Hairsine chart may be accurately employed when there is uniform surcharge. In addition, instead of interpolating Hairsine curves, a suggestion is made to draw the curves for the particular design parameters and obtain the envelope directly through the use of a spreadsheet.
Restrained Teaching: The Common Core of Didaktik
Authors: Hopmann Stefan
Published: May 2007

Didaktik is at the centre of most school teaching and teacher education in Continental Europe, but at the same time almost unknown in the English speaking world. The article gives a brief outline of the history and the common core of Didaktik, of its current situation, and of the basic differences compared to the Anglo-American concept of ‘curriculum and instruction’ and the French ‘transposition didactique’. The common core of Didaktik is characterised as ‘restrained teaching’, based on (a) a commitment to Bildung, (b) the educative difference of matter and meaning, and (c) the autonomy of teaching and learning.
The Building of a New Academic Field: The Case of French Didactiques
Authors: Caillot Michel
Published: May 2007

In this article, the author attempts to show how French disciplinary didactiques were created and have developed. At the beginning, nobody could forecast the future and whether the didactiques would one day be recognised by the academic and instructional systems. The French didactiques are strongly based on school subject matters. Since the creation of Instituts Universitaire de Formation des Maîtres (University Teacher Training Institutes) in 1991, they are completely integrated in French educational research and training systems: a major evolution in education that has taken about 40 years. More recently, a new field of research is developing in the French-speaking area: comparative didactics that groups together disciplinary didacticians in a true research programme.
Didactics, Sense Making, and Educational Experience
Authors: Meyer Meinert A.
Published: May 2007

This article focuses on student participation in classrooms. It aims to demonstrate that effective cultivation of educational experience in schools will lead to a new perspective on the process of teaching and learning. There are no privileged methods of teaching and learning, but most of the teachers have in mind some fuzzy ideas of what good instruction is, and there is a great variety of how teachers involve their students and how students get involved in what happens in school. That is why the student's didactic competence should be used in the instructional process and teachers' and students' sensitivity for classroom participation and student involvement should be increased. Examples of how learners view their educational process, and how sense making can be identified and described, are given. Sense making is an individual affair, and what the teachers want is not necessarily in accord with the students' constructions. Therefore, it is not only of interest to examine how learners acquire knowledge and skills but also how they develop the ability to decide things for themselves and act responsibly in an increasingly complex and difficult world.
Orofaciodigital Syndrome Type IV (Mohr-Majewski Syndrome): Report of a Family with Two Affected Siblings
Authors: Kahl Philip , Heukamp Lukas Carl , Buettner Reinhard , Friedrichs Nicolaus , Roesing Bettina , Knopfle Gisela
Published: May 2007

We report on sibling fetuses with orofaciodigital syndrome (OFDS) type IV (Mohr-Majewski syndrome). The 1st was a 13-week-old fetus with hypertelorism; a median cleft defect of the upper lip, soft palate, and uvula; a polypoid lower lip and multiple frenula of the tongue adherent to the mandible; a congenital heart defect; pre- and postaxial polydactyly of the upper and preaxial polydactyly of the lower limbs; and an intersex genitalia. However, the shortening of both arms and forearms was particularly striking, with shortening of the ulna and ulnar deviation of both hands. The 2nd fetus was of the same parents, was 11 weeks old, and presented with a similar spectrum of malformations. The features of both fetuses showed a transitional phenotype between the OFDS type II (Mohr syndrome) and the short rib–polydactyly syndrome type II (Majewski syndrome), thus extending the known spectrum of the OFDS type IV.
Anaplastic Large Cell Lymphomas: A Study of 75 Pediatric Patients
Authors: d'Amore E.S.G. , Menin A. , Bonoldi E. , Bevilacqua P. , Cazzavillan S. , Donofrio V. , Gambini C. , Forni M. , Gentile A. , Magro G. , Boldrini R. , Pillon M. , Rosolen A. , Alaggio R.
Published: May 2007

In this article, we describe the morphologic and immunophenotypic features of 75 cases of pediatric anaplastic large cell lymphoma (ALCL). According to the World Health Organization classification, 49 cases were common subtype ALCL, and respectively, 3, 6, and 17 cases were small cell, lymphohistiocytic, or mixed histologic variants. Anaplastic lymphoma kinase positivity was detected in 90.7% of the tumors and, using a panel of 9 T-cell surface markers, 88% could be assigned to the T-cell lineage. A molecular analysis for the T-cell receptor γ (TCR- γ) and the heavy chain of the immunoglobulin H rearrangements was performed on 6/9 ALCLs with a null immunophenotype, and a TCR clonal pattern was detected in 5/6 cases. In addition, 94.1% were immunoreactive for 1 or more cytotoxic proteins (Tia1, granzyme B, or perforin), and 15% expressed CD56. Clusterin, CD83, and Pax5, respectively, expressed in 91.3%, 1.7%, and 0% of the ALCLs, were useful biomarkers for the differential diagnosis with Hodgkin's lymphomas.
A Case of Composite Neuroblastoma Composed of Histologically and Biologically Distinct Clones
Authors: Sano Hideki , Gonzalez-Gomez Ignacio , Wu Shi Qi , Armenian Saro H. , Jubran Rima F. , Shimada Hiroyuki
Published: May 2007

We report a case of a 12-month-old girl with stage 3 neuroblastoma composed of 2 distinct clones in the adrenal primary tumor. One clone showed neuroblastoma, poorly differentiated subtype with a low mitosis-karyorrhexis index (favorable histology), and the other was neuroblastoma, poorly differentiated subtype with a high mitosis-karyorrhexis index (unfavorable histology), according to the International Neuroblastoma Pathology Classification. Fluorescent-labeled in-situ hybridization using the formalin-fixed, paraffin-embedded material showed that the MYCN oncogene was amplified in the latter clone but not in the former clone. Lymph nodes from ipsilateral and contralateral sides contained metastatic neuroblastoma of the latter clone. It is well documented that tumors in the Ganglioneuroblastoma, nodular (composite, Schwannian stroma-rich/stroma-dominant and stroma-poor) category are composite and composed of multiple clones. To our knowledge, however, this is the 1st case report of composite tumor with biologically favorable and unfavorable clones in the Neuroblastoma (Schwannian stroma-poor) category.
Accessory Liver Lobe with Mesothelial Inclusion Cysts in an Omphalocele: A New Malformative Association
Authors: Rougemont Anne-Laure , Sartelet Hervé , Oligny Luc L. , Bensoussan Arie , Yazbeck Salam , Fournet Jean-Christophe
Published: May 2007

Mesothelial inclusion cysts represent benign lesions that have been reported in a wide variety of locations. Peritoneal cysts are observed and visceral involvement has been described, notably of intraperitoneal organs such as the spleen and the testis. We report the cases of 2 neonates who underwent surgical management of an omphalocele. The hernial sac contained an accessory liver lobe, displaying in both cases multilocular mesothelial inclusion cysts. The hobnail cells lining the cysts exhibited calretinin and cytokeratin immunohistochemical reactivity, as well as focal D2–40 reactivity. One of the cases occurred in the setting of a Beckwith-Wiedemann syndrome (MIM 130650), an overgrowth disorder notably associated with omphalocele and hepatic anomalies and tumors. However, no hepatic mesothelial cyst has been described in this syndrome. In the 2nd case the omphalocele and the hepatic cysts were the sole lesions observed in the neonate. To the best of our knowledge, these 2 cases represent the first description of such an association.
Untersuchungen zu ausgewählten mechanischen Eigenschaften von Eschenholz | Investigation into certain mechanical properties of ash
Authors: Bonoli Cosma , Niemz Peter , Mannes David
Published: May 2007

Ash originating from two locations in Switzerland was investigated for certain selected mechanical properties. Values were determined for raw density, sorption, swelling, tensile strength,MOE and work on bending strength as well as annual rings. In addition the influence of wood humidity on the tensile strength was investigated as well as the correlation between humidity/tensile strength and annual rings density. The samples, as expected,were generally tough as far as breakage is concerned and the breakage energy required was higher than that of spruce. In view of its relative robustness and strong mechanical properties, there is a potential for the use of ash for the production of layered boards, but also for other wood parts for construction purposes with high requirements.
Anrechnung der CO2-Senken des Schweizer Waldes: Grundlagenpapier und Empfehlungen | Accounting of CO2 sinks in Swiss forests. Working paper and recommendations
Authors: Wald- und Arbeitsgruppe , Klimaschutz Holzwirtschaft im
Published: May 2007

With the ratification of the Kyoto Protocol aimed at reducing greenhouse gases, Switzerland is committed to reducing CO2emissions by 4.2 million tonnes by 2008. The forests in Switzerland could contribute to the country's national carbon balance with maximum 1.8 million tonnes reduction of CO2. With an increased use of the forest the emissions could be reduced by up to 2 million tonnes by the substitution of other materials. With a targeted forest management policy carbon sink reduction and the substitution value of the forest could be balanced against one another. In the framework of climate policy the Federal government should create the legal and organisational conditions for this.
Auf dem Weg zum Gebirgsplenterwald: Kurzzeiteffekte von Durchforstungen auf die Struktur subalpiner Fichtenwälder | On the way to a mountain selection forest:Short-term effects of thinning on the structure of subalpine spruce forests (reviewed paper)
Authors: Bachofen Hansheinrich , Zingg Andreas
Published: May 2007

Stand structures and stand stability in unmanaged Norway spruce forests in the Swiss mountains may decline and their protective function against natural hazards will thus be put at risk. They are being subjected to thinning operations to improve stability and, in the long-term, to transform them into mountain selection forests. On pairs of research plots – thinned and not thinned – we will closely follow the stand development. Preliminary results indicate that the best variables to describe the effectiveness of the applied treatment to the stand structures are the h/d ratio,the spatial distribution and the stand density index.
Räumliche Verteilung der Naturverjüngung auf grossen Lothar-Sturmflächen | Spatial distribution of natural regeneration on large windthrow areas created by the hurricane Lothar in 1999 (reviewed paper)
Authors: Brang Peter
Published: May 2007

Natural regeneration data sampled on 1293 plots from nine windthrow areas were analysed using Cox's (1971)method of zero-plot-diagrams. Average sapling density was 600 to 6500 saplings ha–1. Sapling counts indicated higher clumping than would occur with a random distribution of 1000 saplings ha–1. From 2001 to 2004, the clumpiness of the natural regeneration increased, and the establishment of additional seedlings was positively correlated with seedling presence in 2001.
Association of Occlusive Retinal Vasculitis With Intravitreal Faricimab
Authors: Li Ye , Chong Robert , Fung Adrian T.
Published: March 2024

This case report describes a patient with attenuation of retinal arterioles and veins associated with 2 blot hemorrhages and pallor of the inferotemporal retina without emboli.
N6‐isopentenyladenosine inhibits aerobic glycolysis in glioblastoma cells by targeting PKM2 expression and activity
Authors: Pagano Cristina , Coppola Laura , Navarra Giovanna , Avilia Giorgio , Savarese Beatrice , Torelli Giovanni , Bruzzaniti Sara , Piemonte Erica , Galgani Mario , Laezza Chiara , Bifulco Maurizio
Published: March 2024

Glioblastoma (GBM) is a primary tumor in the central nervous system with poor prognosis. It exhibits elevated glucose uptake and lactate production. This metabolic state of aerobic glycolysis is known as the Warburg effect. N6‐isopentenyladenosine (iPA), a natural cytokine modified with an isopentenyl moiety derived from the mevalonate pathway, has well‐established anti‐tumor activity. It inhibits cell proliferation in glioma cells, inducing cell death by apoptosis and/or necroptosis. In the present study, we found that iPA inhibits aerobic glycolysis in unmodified U87MG cells and in the same cell line engineered to over‐express wild‐type epidermal growth factor receptor (EGFR) or EGFR variant III (vIII), as well as in a primary GBM4 patient‐derived cell line. The detection of glycolysis showed that iPA treatment suppressed ATP and lactate production. We also evaluated the response of iPA treatment in normal human astrocyte primary cells, healthy counterpart cells of the brain. Aerobic glycolysis in treated normal human astrocyte cells did not show significant changes compared to GBM cells. To determine the mechanism of iPA action on aerobic glycolysis, we investigated the expression of certain enzymes involved in this metabolic pathway. We observed that iPA reduced the expression of pyruvate kinase M2 (PKM2), which plays a key role in the regulation of aerobic glycolysis, promoting tumor cell proliferation. The reduction of PKM2 expression is a result of the inhibition of the inhibitor of nuclear factor kappa‐B kinase subunit, beta/nuclear factor‐kappa B pathway upon iPA treatment. In conclusion, these experimental results show that iPA may inhibit aerobic glycolysis of GBM in stabilized cell lines and primary GBM cells by targeting the expression and activity of PKM2.
Electro‐Conductive Ti3C2 MXene Multilayered Membranes: Dye Removal and Antifouling Performance
Authors: Zandi Zahra , Rastgar Masoud , Mohseni Mojtaba , Firouzjaei Mostafa Dadashi , Dilokekunakul Waralee , Anasori Babak , Vecitis Chad D. , Keller Robert , Wessling Matthias , Elliott Mark , Rahimpour Ahmad , Sadrzadeh Mohtada
Published: March 2024

This work describes the fabrication of a novel electroconductive membrane made of Ti3C2Tx (MXene) nanosheet coating through a one‐step pressure‐assisted technique. Ti3C2‐MXene is firmly attached over a polyamide–imide (PAI) microfilter by employing a binder composed of carboxymethyl cellulose (CMC)/glutaraldehyde (GA). Through coating a proper amount of multilayer Ti3C2‐MXene, the electrical conductivity of 174 ± 0.16 S m−1 is achieved. The rejection rates of reactive red 120 (RR120), reactive black (RB), and methyl orange (MO) by the pristine PAI membrane are 45.2%, 40.81%, and 33.65%, respectively. However, rejection rates significantly improve with the Ti3C2 MXene coating to over 99.71%, 97.95%, and 68.91% for RR120, RB, and MO. Applying a 4 V cathodic potential resulted in a flux recovery ratio (FRR) of 99.83% and a flux decline rate (FDR) of less than 1% during humic acid (HA) filtration. Without applying voltage, the MXene‐coated membrane shows an FRR and FDR of 92.51% and 45.56%, respectively. Surface energy analysis reveals strong repulsive interactions between foulants and the membrane surface. Moreover, the surface free energy indicates that foulants such as sodium alginate (SA) and bovine serum albumin (BSA) exhibit stronger adhesion to the membrane than HA, consistent with the fouling experiment results.
STING Membrane Prevents Post‐Surgery Tissue Adhesion and Tumor Recurrence of Colorectal Cancer
Authors: Li Jianlin , Yu Haiwang , Kang Yan , Niu Kun , Wang Ming , Jiang Yitong , Jiang Ni , Ding Zhenshan , Gan Zhihua , Yu Qingsong
Published: March 2024

Surgery is the standard treatment regimen for resectable colorectal cancer (CRC). However, it is very hard to completely remove all cancer cells in clinical practice, leading to the high recurrence rates of the disease. Moreover, the post‐surgery tissue adhesion greatly prevents the possibility of reoperation, significantly limiting the long‐term surviving of CRC patients. To overcome CRC recurrence and avoid the post‐surgery tissue adhesion, this work develops a novel stimulator of interferon genes “STING” membrane based on the coaxial electrospinning technology and hyaluronic acid modification. A reactive oxygen species responsive prodrug of gambogic acid (GB) and a potent STING agonist (CDN) are coloaded in the core–shell structure of the membrane, which endows the loaded drug with sustained and sequential release patterns. The localized delivery of GB and CDN can selectively induce efficient immunogenic cell death of cancer cells and then evoke the systemic anticancer immunity by activating the Cyclic GMP‐AMP (cGAMP) synthase/STING pathway. As‐designed “STING” membrane not only safely prevents tumor recurrence through the synergistic chemoimmunotherapy but also efficiently avoids the post‐surgery tissue adhesion, facilitating the clinical intervention of CRC.
Advanced Dielectric Materials for Triboelectric Nanogenerators: Principles, Methods, and Applications
Authors: Li Yi , Luo Yi , Deng Haocheng , Shi Shengyao , Tian Shuangshuang , Wu Haoying , Tang Ju , Zhang Cheng , Zhang Xiaoxing , Zha Jun‐Wei , Xiao Song
Published: March 2024

Triboelectric nanogenerator (TENG) manifests distinct advantages such as multiple structural selectivity, diverse selection of materials, environmental adaptability, low cost, and remarkable conversion efficiency, which becomes a promising technology for micro‐nano energy harvesting and self‐powered sensing. Tribo‐dielectric materials are the fundamental and core components for high‐performance TENGs. In particular, the charge generation, dissipation, storage, migration of the dielectrics, and dynamic equilibrium behaviors determine the overall performance. Herein, a comprehensive summary is presented to elucidate the dielectric charge transport mechanism and tribo‐dielectric material modification principle toward high‐performance TENGs. The contact electrification and charge transport mechanism of dielectric materials is started first, followed by introducing the basic principle and dielectric materials of TENGs. Subsequently, modification mechanisms and strategies for high‐performance tribo‐dielectric materials are highlighted regarding physical/chemical, surface/bulk, dielectric coupling, and structure optimization. Furthermore, representative applications of dielectric materials based TENGs as power sources, self‐powered sensors are demonstrated. The existing challenges and promising potential opportunities for advanced tribo‐dielectric materials are outlined, guiding the design, fabrication, and applications of tribo‐dielectric materials.
Laser‐Synthesized Germanium Nanoparticles as Biodegradable Material for Near‐Infrared Photoacoustic Imaging and Cancer Phototherapy
Authors: Belyaev Iaroslav B. , Zelepukin Ivan V. , Kotelnikova Polina A. , Tikhonowski Gleb V. , Popov Anton A. , Kapitannikova Alina Yu. , Barman Jugal , Kopylov Alexey N. , Bratashov Daniil N. , Prikhozhdenko Ekaterina S. , Kabashin Andrei V. , Deyev Sergey M. , Zvyagin Andrei V.
Published: March 2024

Biodegradable nanomaterials can significantly improve the safety profile of nanomedicine. Germanium nanoparticles (Ge NPs) with a safe biodegradation pathway are developed as efficient photothermal converters for biomedical applications. Ge NPs synthesized by femtosecond‐laser ablation in liquids rapidly dissolve in physiological‐like environment through the oxidation mechanism. The biodegradation of Ge nanoparticles is preserved in tumor cells in vitro and in normal tissues in mice with a half‐life as short as 3.5 days. Biocompatibility of Ge NPs is confirmed in vivo by hematological, biochemical, and histological analyses. Strong optical absorption of Ge in the near‐infrared spectral range enables photothermal treatment of engrafted tumors in vivo, following intravenous injection of Ge NPs. The photothermal therapy results in a 3.9‐fold reduction of the EMT6/P adenocarcinoma tumor growth with significant prolongation of the mice survival. Excellent mass‐extinction of Ge NPs (7.9 L g−1 cm−1 at 808 nm) enables photoacoustic imaging of bones and tumors, following intravenous and intratumoral administrations of the nanomaterial. As such, strongly absorbing near‐infrared‐light biodegradable Ge nanomaterial holds promise for advanced theranostics.
Decline in pubertal timing and its relationship with excess weight. A study of the secular trend in age at menarche in girls from La Plata district (Buenos Aires, Argentina)
Authors: Torres María Fernanda , Garraza Mariela , Quintero Fabián Aníbal , Luna María Eugenia , Navazo Bárbara , Cesani María Florencia
Published: March 2024

Objective

To provide information on the secular trend in age at menarche (AgM) in Argentinean girls in relation to excess weight (EW) and body adiposity.

Methods

Two cohorts (C) (C1, 2005–2007 and C2, 2015–2019) of children aged 8–14 years from La Plata district were studied using identical methodological criteria. Each participating child was asked about menarche (M) status: M presence (MP) or absence (MA). The AgM was estimated using the status quo method and logistic regression analysis. Body weight, height, and tricipital and subscapular skinfolds were collected to estimate EW (overweight + obesity) according to WHO criteria, and body adiposity (sum of skinfolds, SSK = [tricipital + subscapular]). The prevalence of EW by C was estimated and compared using the Chi‐square test. The MP probability in relation to age, C, and EW was analyzed by applying logistic regression. Parents completed a questionnaire to assess family socioeconomic conditions. Data were compared using the Chi‐square test.

Results

Differences in MP prevalence between C were significant (C1: 21.1% vs. C2: 28.7%). Median AgM was 12.81 years in C1 and 12.22 in C2. The prevalence of EW was higher in C2 (35.3%) than in C1 (24.6%). The probability of MP was higher in C2 than in C1 and children with EW. Both BMI and SSK showed inter‐cohort increases. Socioeconomic conditions were substantially deteriorated between C.

Conclusion

In an obesogenic context marked by the significant increase in body adiposity and EW, M prevalence exhibited a positive secular trend and AgM reduced by nearly seven months between the cohorts studied.
Intrinsic RNA Targeting Triggers Indiscriminate DNase Activity of CRISPR‐Cas12a
Authors: Zhang Jiongyu , Li Ziyue , Guo Chong , Guan Xin , Avery Lori , Banach David , Liu Changchun
Published: March 2024

The CRISPR‐Cas12a system has emerged as a powerful tool for next‐generation nucleic acid‐based molecular diagnostics. However, it has long been believed to be effective only on DNA targets. Here, we investigate the intrinsic RNA‐enabled trans‐cleavage activity of AsCas12a and LbCas12a and discover that they can be directly activated by full‐size RNA targets, although LbCas12a exhibits weaker trans‐cleavage activity than AsCas12a on both single‐stranded DNA and RNA substrates. Remarkably, we find that the RNA‐activated Cas12a possesses higher specificity in recognizing mutated target sequences compared to DNA activation. Based on these findings, we develop the “Universal Nuclease for Identification of Virus Empowered by RNA‐Sensing” (UNIVERSE) assay for nucleic acid testing. We incorporate a T7 transcription step into this assay, thereby eliminating the requirement for a protospacer adjacent motif (PAM) sequence in the target. Additionally, we successfully detect multiple PAM‐less targets in HIV clinical samples that are undetectable by the conventional Cas12a assay based on double‐stranded DNA activation, demonstrating unrestricted target selection with the UNIVERSE assay. We further validate the clinical utility of the UNIVERSE assay by testing both HIV RNA and HPV 16 DNA in clinical samples. We envision that the intrinsic RNA targeting capability may bring a paradigm shift in Cas12a‐based nucleic acid detection and further enhance the understanding of CRISPR‐Cas biochemistry.
Modulation der Steifigkeit und Pulsierende Freisetzung in Dual‐Responsiven Hydrogelen
Authors: Jain Mehak , Trapani Giuseppe , Trappmann Britta , Ravoo Bart Jan
Published: March 2024

Nach dem Vorbild der Natur kann Selbstregulierung synthetischer Hydrogele durch chemomechanische Signale oder chemische Reaktionsnetzwerke eingebaut werden, um die physikochemischen Eigenschaften des Materials aufrecht zu erhalten oder anzupassen, wenn sie externen Stimuli ausgesetzt werden. In dieser Arbeit stellen wir Hydrogele vor, welche auf Redox‐ und Lichtstimuli reagieren und in der Lage sind, das polymere Netzwerk schnell zu verändern und gleichzeitig die Stabilität des Hydrogels zu erhalten. Bei Bestrahlung mit UV‐Licht zeigen die Polymerhydrogele, welche redoxresponsiv über Disulfide quervernetzt sind und lichtresponsive ortho‐Nitrobenzyleinheiten tragen, eine Freisetzung ihrer Ladung mit gleichzeitiger Anpassung des Hydrogelnetzwerks zu höherer Steifigkeit aufgrund der in situ Vernetzung durch S‐Nitrosylierung. Während das Hydrogeldesign es ermöglicht, dass das Netzwerk entweder in Gegenwart des Reduktionsmittels Glutathion weicher oder bei UV‐Bestrahlung steifer wird, führt die gleichzeitige Anwendung beider Stimuli zu einer Selbstregulierung des Netzwerks, was zu einer pulsierenden Freisetzung der Ladung der Hydrogele führt. Schließlich wurde die adaptive Steifigkeit genutzt, um einstellbare Hydrogele als Substrate für verschiedene Zelllinien herzustellen.
Dividing‐wall column for separating wide boiling mixture: Optimal design and servo control strategy
Authors: Aurangzeb Md , Banerjee Sudip , Roy Subhankar , Tejasvi Ravi
Published: March 2024

The dividing‐wall column (DWC) stands as an energy‐efficient distillation technology designed to efficiently separate ternary systems into their pure components within a single column. Despite its efficiency, integrating two towers into a DWC poses challenges in controllability. Published studies have focused on developing controllers for disturbance rejection but have not addressed the issue of servo control. Addressing this, our study proposes a servo controller problem and a methodical approach to strategically select controlled variables that undergo consecutive set point step changes, aiming to track the purity of key products obtained from the DWC. To achieve this goal, we developed a dynamic model specifically tailored to the DWC. Determining the design parameters involved employing a genetic algorithm optimization technique, minimizing the total annual cost. Subsequently, we implemented three servo parallel proportional‐integral (PI) feedback controllers for three distinct product streams. The fine‐tuning of their controller gain and reset time is carried out by minimizing the integrated square error while adhering to valve opening constraints. Our investigation revealed a limitation: the introduction of simultaneous step changes in all three controlled variables proved unfeasible with the three active PI controllers. As an alternative, our findings recommend prioritizing two variables: the lightest (distillate) and heaviest (bottom) key components, alongside the middle component (side stream) and either the lightest or heaviest key component. This research underscores the complexities of implementing step changes in multiple controlled variables within a DWC, offering insights into optimal control strategies for enhancing the efficiency of this innovative distillation technology.
Inspired anatomy education: Might God be relevant?
Authors: Sullivan Sean P. , Barnes Jonathan
Published: March 2024

Anatomy education is essential for developing healthcare professionals, and discussion continues about factors that impact and improve the anatomy learning environment. Neglected in this discussion is a consideration of the diverse religious assumptions and beliefs that college students bring to anatomy learning. Surveys of religion among United States college students indicate that many identify as religious and Christian. This viewpoint commentary summarizes main elements of Christian theology and anthropology, discusses the holistic and positive view of the body presented in Christian scripture, and outlines how these Christian beliefs inform and impact student preparation for anatomy education and human body dissection, address ethical issues in body donation, and support professionalism for future career practice.
Light Responsive DNA Nanomaterials and Their Biomedical Applications
Authors: Aqib Raja Muhammad , Umer Arsalan , Li Jialin , Liu Jianbing , Ding Baoquan
Published: March 2024

DNA nanomaterials have been widely employed for various biomedical applications. With rapid development of chemical modification of nucleic acid, serials of stimuli‐responsive elements are included in the multifunctional DNA nanomaterials. In this review, we summarize the recent advances in light responsive DNA nanomaterials based on photocleavage/photodecage, photoisomerization, and photocrosslinking for efficient bioimaging (including imaging of small molecule, microRNA, and protein) and drug delivery (including delivery of small molecule, nucleic acid, and gene editing system). We also discuss the remaining challenges and future perspectives of the light responsive DNA nanomaterials in biomedical applications.
The effect of thyme essential oil and endothelial progenitor stem cells on lipopolysaccharide‐induced sepsis in C57BL/6 mice
Authors: Soltan Dallal Mohammad Mehdi , Siavashi Maryam , Karimaei Samira , Siavashi Vahid , Abdi Milad , Yaseri Mehdi , Razavi Seyed Alireza , Bakhtiari Ronak
Published: March 2024

Sepsis is a potentially fatal syndrome related to severe systemic inflammation developed by infection. Despite different antimicrobial therapies, morbidity and mortality rates remain high. Herbs along with cell therapy have been introduced as a promising option to improve the symptoms of sepsis. The present study aimed to evaluate the therapeutic effect of simultaneous administration of thyme essential oil (TEO) and endothelial progenitor stem cells (EPCs) on lipopolysaccharide (LPS)‐induced sepsis in C57BL/6 mice. Sepsis was induced in C57Bl/6J mice by intraperitoneal injection of LPS, followed 2 h later by an intravenous injection of EPCs or oral administration of TEO or simultaneous administration of TEO and EPCs. After 10 days, the complete blood cell, renal and liver factors, serum levels of inflammatory cytokines, and angiogenic factors were measured. Simultaneous treatment with EPCs and TEO significantly increased the survival of mice with sepsis and modulated the inflammatory response by reducing the serum levels of pro‐inflammatory cytokines. Moreover, this treatment significantly reduced the level of white blood cells and neutrophils and increased the number of red blood cells, the percentage of hematocrit, and hemoglobin. The combination of TEO with EPCs decreased organ injuries and was assessed by lower levels of the liver enzymes alanine aminotransferase and aspartate aminotransferase compared to the sepsis group. Administration of EPCs and TEO also significantly improved angiogenic factors, lung function, and toll‐like receptor 4 expression. EPCs in combination with TEO increase survival in the LPS‐induced sepsis mice model by acting on several targets. Thus, the combination of TEO with EPCs can be a feasible approach for the future clinical treatment and control of sepsis.
Stereotypes and unconscious bias in institutional child sexual abuse: Barriers to identification, reporting and prevention
Authors: Arnold Suzanne , Jeglic Elizabeth L.
Published: March 2024

Child sexual abuse within institutional settings has been a major concern for governments around the world for many years. Consequently, prevention policies have been developed, and institutional child abuse laws have been strengthened in many jurisdictions. Legislation is important to prevent reoffending, however, the majority of childhood sexual abuse remains unreported and undetected. While awareness of the failings of institutions to properly identify and respond to child abuse has grown in recent years, barriers to reporting institutional abuse remain understudied, impacting the ability to prevent abuse. One possible reason that prevents workers from identifying and reporting child sexual abuse is that their judgements are vulnerable to stereotypes and unconscious biases about who perpetrates and is victimised by sexual crimes and what constitutes warning signs of sexually abusive behaviours. Research in psychology provides key insights into human reasoning processes that can lead to bias, so workers fail to identify, respond and prevent grooming and child abuse in an organisational context. This paper reviews what is known about the development and maintenance of stereotypes and unconscious bias, their role in institutional sexual abuse, and concludes with a discussion of measures that can be taken to mitigate unconscious bias to prevent child abuse.
Sudden onset of symptoms in concurrent Takayasu arteritis and Ulcerative colitis: A case report with neurological complications
Authors: Khalaji Amirreza , Mahdian Taha , Eftekharsadat Amir Taher , Jafarpour Mehdi
Published: March 2024

Key Clinical Message

The rare co‐occurrence of takayasu arteritis (TAK) and ulcerative colitis (UC), presenting with asymptomatic onset and neurological complications, highlights the importance of an integrated diagnostic approach for overlapping autoimmune conditions.

We present a rare case of a 44‐year‐old female diagnosed with both UC and TAK, characterized by an unusual acute asymptomatic onset accompanied by neurological manifestations. The patient exhibited symptoms of acute ischemic stroke along with vascular abnormalities, as well as colon inflammation associated with UC. The patient's asymptomatic presentation at the onset differs from previously reported cases. The presence of additional complications, such as hepatocellular adenoma and primary sclerosing cholangitis, further complicated the diagnostic challenges. The patient's treatment involved a combination of methylprednisolone, azathioprine, and prednisolone leading to improved clinical outcomes. This case emphasizes the complexity involved in diagnosing overlapping conditions and highlights the significance of TAK in presenting atypical manifestations in relation to UC. Furthermore, this case contributes to the limited literature, underscoring the need for early detection and comprehensive treatment approaches.
Asymptomatic paroxysmal ventricular standstill in an elderly male following revascularization of multivessel coronary disease: A case report and literature review
Authors: Sagalov Andrew , Maryala Shashi , Kulkarni Abhishek , Hegde Shruti , Labedi Mohamed
Published: March 2024

Key Clinical Message

Ventricular standstill is a dangerous arrhythmia that requires prompt diagnosis and intervention, especially in patients with structural heart disease. Clinicians should recognize ventricular standstill as a complication of cardiac revascularization and be cognizant of asymptomatic cases necessitating intervention. Early evaluation to facilitate pacemaker implantation portends good outcomes in this patient subgroup.
Abdominal migraine with acute watery diarrhea and dehydration: Successful treatment with Valproic acid in a pediatric case
Authors: Amin Mohammad Ashraful , Manna Ridwana Maher , Nahin Sabrina , Hawlader Mohammad Delwer Hossain
Published: March 2024

Key Clinical Message

Abdominal migraine (AM) is a prevalent pediatric condition that rarely affects adults. Multiple diagnostic criteria have been established, but in general, AM is characterized by unprovoked episodes of acute central abdominal pain with migrainous characteristics and periods of respite. Recurrent stomach pain is a prevalent symptom globally, with a significant portion of cases falling under the category of functional gastrointestinal disorders (FGIDs) due to the absence of identified biological causes. There is a notable prevalence of migraines among individuals with a family history of the condition, indicating a genetic predisposition. A descriptive report has been prepared on the participant who had AM associated with acute watery diarrhea (AWD) on January 2023. The patient's parents had given written informed consent for publishing this case report. In this case report, we present the clinical scenario of a 12‐year‐old male child who experienced AM symptoms alongside a history of absence seizures. The child presented with episodes of abdominal pain and AWD. Despite extensive investigation and treatment, there was no improvement in abdominal pain. However, after 1 week of oral valproic acid administration, the patient remained symptom‐free during the follow‐up period. Dehydration, along with other factors, has been identified as a triggering factor for AM. Acute watery diarrhea has the potential to disrupt the normal functioning of the gastrointestinal system, and dehydration may lead to subsequent abdominal symptoms.
Confinement Effects in Catalysis: Steering the Product Selectivity in Cannabidiol Isomerization by the Resorcinarene Supramolecular Capsule
Authors: Bordignon Francesca , Calmanti Roberto , Perosa Alvise , Fabris Fabrizio , Scarso Alessandro
Published: March 2024

The supramolecular hydrogen‐bonded self‐assembled resorcinarene hexameric capsule promotes the ring closing isomerization of cannabidiol through encapsulation of the intermediate carbocation species formed by protonation with HCl. The confinement effect imparted by the capsule steers product selectivity towards the uncommon products Δ8‐iso‐THC, Δ4(8)‐iso‐THC, together with the hydrated 8‐Hydroxy‐iso‐THC.
Synthesis and Structural Revision of a Natural Tetrasaccharide from StarfishAsterias rollestoniBell
Authors: Liu Ao , Gao Longwei , Tang Xintong , Yang Xudong , Liu Xianglai , Xie Weijia , Qi Jin , Li Wei
Published: March 2024

Starfish provide important saponins with diverse bioactivities as the secondary metabolites, among which 2‐O‐glycosylated glycosides are commonly found. Preparation of those 1,2‐trans2‐O‐glycosylated glycosides usually relies on 2‐O‐acyl participation requiring the selective installation and cleavage of 2‐O‐acyl groups. A convergent synthesis using 2‐O‐glycosylated oligosaccharide donors would be more straightforward but also pose greater challenges. Herein, we report a convergent synthesis of a distinctive tetrasaccharide isolated from starfishAsterias rollestoniBell. Dual 2‐(diphenylphosphinoyl)acetyl (DPPA) groups at O3 and O4 on galactose moiety led to high β‐selectivities (β/α=12/1 or β only) in the challenging [2+2] glycosylation, giving the desired tetrasaccharides in >90 % yields from the 2‐O‐glycosylated disaccharide donors. These synthetic studies have also unambiguously revised the structure of these natural tetrasaccharides. This work would facilitate further studies on new inhibitors of α‐glucosidase as hypoglycemic drugs.
Development of Benzimidazole‐Substituted Spirocyclopropyl Oxindole Derivatives as Cytotoxic Agents: Tubulin Polymerization Inhibition and Apoptosis Inducing Studies
Authors: Sakla Akash P. , Bazaz Mohd Rabi , Mahale Ashutosh , Sharma Pravesh , Valapil Durgesh Gurukkala , Kulkarni Onkar Prakash , Dandekar Manoj P. , Shankaraiah Nagula
Published: March 2024

A series of spirocyclopropyl oxindoles with benzimidazole substitutions was synthesized and tested for their cytotoxicity against selected human cancer cells. Most of the molecules exhibited significant antiproliferative activity with compound 12 p being the most potent. It exhibited significant cytotoxicity against MCF‐7 breast cancer cells (IC50 value 3.14±0.50 μM), evidenced by the decrease in viable cells and increased apoptotic features during phase contrast microscopy, such as AO/EB, DAPI and DCFDA staining studies. Compound 12 p also inhibited cell migration in wound healing assay. Anticancer potential of 12 p was proved by the inhibition of tubulin polymerization with IC50 of 5.64±0.15 μM. These results imply the potential of benzimidazole substituted spirocyclopropyl oxindoles, notably 12 p, as cytotoxic agent for the treatment of breast cancer.
Cancer‐related thrombotic microangiopathy and disseminated intravascular coagulation in a patient with bone marrow carcinomatosis of unknown primary origin: A case report
Authors: Manabe Masahiro , Inano Naoyuki , Hagiwara Yuuji , Sogabe Nobuhiro , Nanno Satoru , Mazaki Takeshi , Koh Ki‐Ryang
Published: March 2024

Background

Cancer‐related thrombotic microangiopathy (CR‐TMA) is a rare type of Coombs‐negative hemolytic anemia, which is caused by malignancy and has a poor prognosis.

Case

A 76‐year‐old female was referred to our hospital due to Coombs‐negative hemolytic anemia, which was causing fatigue and dyspnea on exertion, accompanied by schistocytosis. A bone marrow examination demonstrated bone marrow carcinomatosis, and the tumor cells were morphologically suspected to be signet‐ring cell carcinoma cells. As we failed to find the primary tumor site before the patient died, she was diagnosed with CR‐TMA due to bone marrow carcinomatosis of unknown primary origin. Thrombotic thrombocytopenic purpura (TTP) was rapidly ruled out based on her PLASMIC score. In addition, immunohistochemical staining of a clot section of the bone marrow and tumor marker data were useful for narrowing down the likely primary tumor site.

Conclusion

Although CR‐TMA is an extremely rare phenomenon, clinicians who suspect CR‐TMA should quickly rule out TTP and decide whether to provide appropriate chemotherapy or plan for palliative care.
Structure‐Guided Evolution of Cyclohexanone Monooxygenase Toward Bulky Omeprazole Sulfide: Substrate Migration and Stereoselectivity Inversion
Authors: Wei Shiyu , Xu Guochao , Zhou Jieyu , Ni Ye
Published: March 2024

Structure‐guided engineering of a CHMO from Amycolatopsis methanolica (AmCHMO) was performed for asymmetric sulfoxidation activity and stereoselectivity toward omeprazole sulfide. Initially, combinatorial active‐site saturation test (CASTing) and iteratively saturation mutagenesis (ISM) were performed on 5 residues at the “bottleneck” of substrate tunnel, and MT3 was successfully obtained with a specific activity of 46.19 U/g and R‐stereoselectivity of 99 % toward OPS. Then, 4 key mutations affecting the stereoselectivity were identified through multiple rounds of ISM on residues at the substrate binding pocket region, resulting MT8 with an inversed stereoselectivity from 99 % (R) to 97 % (S). MT8 has a greatly compromised specific activity of 0.08 U/g. By introducing additional beneficial mutations, MT11 was constructed with significantly increased specific activity of 2.29 U/g and stereoselectivity of 97 % (S). Enlarged substrate tunnel is critical to the expanded substrate spectrum of AmCHMO, while reshaping of substrate binding pocket is important for stereoselective inversion. Based on MD simulation, pre‐reaction states of MT3‐OPSproR, MT8‐OPSproS, and MT11‐OPSproS were calculated to be 45.56 %, 17.94 %, and 28.65 % respectively, which further confirm the experimental data on activity and stereoselectivity. Our results pave the way for engineering distinct activity and stereoselectivity of BVMOs toward bulky prazole thioethers.