bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian seromucinous carcinoma: an independent epithelial ovarian cancer?
Authors: Hu Yi , Fu Kun , Liu Huining , He Qiongqiong , Qiu Xiaoqin , Yang Wenqing , Zhang Yu
Published: January 2023

Background

2020 World Health Organization Classification of Female Genital Tumors removed ovarian seromucinous carcinoma as a distinct entity and recategorized it as ovarian endometrioid carcinoma with mucinous differentiation according to its pathological features. The aim of this study was to find whether ovarian seromucinous carcinoma truly represented a distinct category of ovarian tumors or an analogue of ovarian endometrioid carcinoma.

Methods

Twelve patients diagnosed with ovarian seromucinous carcinoma and received surgery at the Xiangya Hospital from January 2010 to December 2019 were included in this study. Clinicopathological features such as clinical symptoms, serological indicators, surgical information, postoperative findings, chemotherapy sensitivity, follow-up information, HE staining and IHC staining images and other clinicopathologic features were collected. Using t-test and Kaplan Meier to perform statistical analysis. Pathological review was conducted using the 2014 World Health Organization criteria. All pathological diagnoses were reviewed by two experienced pathologists.

Results

The age of 12 patients diagnosed with ovarian seromucinous carcinoma ranged from 23 to 68 years, with a median age of 46.8 years. Serum level of CA125 was elevated in 10 patients, and CA125/CEA ratio was less than 25 in 6 patients. Eleven patients underwent radical ovarian cancer surgery, and one patient underwent fertility preservation surgery. The progression free survival and overall survival of ovarian seromucinous carcinoma is 46.8 months and 50.2 months. Kaplan-Meier survival curve showed that the prognosis of ovarian seromucinous carcinoma and ovarian endometrioid carcinoma was significantly different (P = 0.03). The prognosis of ovarian seromucinous carcinoma and ovarian mucinous carcinoma was similar.

Conclusion

Although ovarian seromucinous carcinoma and ovarian endometrioid carcinoma are similar in pathologic morphology, their clinical features and prognosis are significantly different. The signs, serum biomarker and prognosis of the ovarian seromucinous carcinoma are similar with ovarian mucinous carcinoma. Therefore, ovarian seromucinous carcinoma is not suitable to be directly classified as ovarian endometrioid carcinoma.
Enhancement of acetate production in hydrogen-mediated microbial electrosynthesis reactors by addition of silica nanoparticles
Authors: Pan Zeyan , Liu Zhuangzhuang , Hu Xiaona , Cui Kai , Cai Wenfang , Guo Kun
Published: January 2023

Microbial electrosynthesis (MES) is a promising technology for CO2 fixation and electrical energy storage. Currently, the low current density of MES limits its practical application. The H2-mediated and non-biofilm-driven MES could work under higher current density, but it is difficult to achieve high coulombic efficiency (CE) due to low H2 solubility and poor mass transfer. Here, we proposed to enhance the hydrogen mass transfer by adding silica nanoparticles to the reactor. At pH 7, 35 ℃ and 39 A·m− 2 current density, with the addition of 0.3wt% silica nanoparticles, the volumetric mass transfer coefficient (kLa) of H2 in the reactor increased by 32.4% (from 0.37 h− 1 to 0.49 h− 1), thereby increasing the acetate production rate and CE of the reactor by 69.8% and 69.2%, respectively. The titer of acetate in the reactor with silica nanoparticles (18.5 g·L− 1) was 56.9% higher than that of the reactor without silica nanoparticles (11.8 g·L− 1). Moreover, the average acetate production rate of the reactor with silica nanoparticles was up to 2.14 g·L− 1·d− 1 in the stable increment phase, which was much higher than the other reported reactors. These results demonstrated that the addition of silica nanoparticles is an effective approach to enhancing the performance of H2-mediated MES reactors.

Graphical Abstract
Verapamil-loaded supramolecular hydrogel patch attenuates metabolic dysfunction-associated fatty liver disease via restoration of autophagic clearance of aggregated proteins and inhibition of NLRP3
Authors: Kim Do Kyung , Han Daewon , Bae Jeongyun , Kim Haeil , Lee Solji , Kim Jong-Seok , Jeong Young-Gil , Shin Jongdae , Park Hwan-Woo
Published: January 2023

Background

Obesity, a serious threat to public health, is linked to chronic metabolic complications including insulin resistance, type-2 diabetes, and metabolic dysfunction-associated fatty liver disease (MAFLD). Current obesity medications are challenged by poor effectiveness, poor patient compliance, and potential side effects. Verapamil is an inhibitor of L-type calcium channels, FDA-approved for the treatment of hypertension. We previously investigated the effect of verapamil on modulating autophagy to treat obesity-associated lipotoxicity. This study aims to develop a verapamil transdermal patch and to evaluate its anti-obesity effects.

Methods

Verapamil is loaded in biomimetic vascular bundle-like carboxymethyl pullulan-based supramolecular hydrogel patches cross-linked with citric acid and glycerol linkages (CLCMP). The investigation was then carried out to determine the therapeutic effect of verapamil-loaded CLCMP (Vera@CLCMP) on diet-induced obese mice.

Results

Vera@CLCMP hydrogel patches with hierarchically organized and anisotropic pore structures not only improved verapamil bioavailability without modifying its chemical structure but also enhanced verapamil release through the stratum corneum barrier. Vera@CLCMP patches exhibit low toxicity and high effectiveness at delivering verapamil into the systemic circulation through the dermis in a sustained manner. Specifically, transdermal administration of this patch into diet-induced obese mice drastically improved glucose tolerance and insulin sensitivity and alleviated metabolic derangements associated with MAFLD. Furthermore, we uncovered a distinct molecular mechanism underlying the anti-obesity effects associated with the hepatic NLR family pyrin domain-containing 3 (NLRP3) inflammasome and autophagic clearance by the vera@CLCMP hydrogel patches.

Conclusion

The current study provides promising drug delivery platforms for long-term family treatment of chronic diseases, including obesity and metabolic dysfunctions.
The interdependency of border bureaucracies and mobility intermediaries: a street-level view of migration infrastructuring
Authors: Infantino Federica
Published: January 2023

Building on the case of visa procedures, this article analyses the relationship between border bureaucracies and intermediaries understood as actors, organisations and knowledge that facilitate, shape, and enable human mobility. I take the street-level view to shed light on the interplay of multiple dimensions and logics, which affects how people are mobile. I argue that the analytical lens of interdependency between dimensions and logics that characterize bureaucracies and intermediaries makes sense of migration infrastructuring processes at the street-level. The case of visa policies and practices, which are characterized by the twofold objective of stemming and spurring mobility, is particularly apt to put forward that intermediaries’ socio-economic activities, which bridge borders, by facilitating, shaping, and sustaining mobility, respond not just to the policies and practices that build and reinforce borders but also to those soliciting certain kinds of mobility. The analysis builds on the comparison of ethnographic literature to put forward three empirical situations that exemplify the dynamics of interdependency: Local guides and experts who develop in response to the opacity of bureaucratic procedures and to the distance between visa applicants and state actors; The providers of pieces of documentation, whether counterfeit or ‘real-but-fake’, who respond to the impossibility of complying with bureaucratic requirements and to restrictive border regimes; Authorized administrative agencies, tour operators, travel agencies, and agencies that facilitate the supplying of specific kinds of workforce, who respond to the objective of soliciting the mobility of tourists, businessmen and workers. The street-level view of migration infrastructuring processes connects the micro-perspective of the trajectory of individuals to macro structures such as policies and drivers of international mobility. The investigation of the effectiveness of these actors and activities in obtaining visas, on which further research could systematically focus, shows that they might produce immobility as well. In a nutshell, (im)mobility also results from the interplay between border bureaucracies and mobility intermediaries.
Effect of atracurium and rocuronium on the state and response entropy during isoflurane anesthesia: randomized prospective study
Authors: Hassanien Noran Essam Mohamed , Bassiouny Mohsen Abdghany , ElSerwi Heba Bahaa Eldin , Ashour Tarek Mohamed Ahmed , Ismaiel Mohamed Abdelmohsen Abdelnaiem
Published: January 2023

Background

Several researches have examined the impact of inhalation anesthetics, intravenous anesthetics, and muscle relaxants on spectral entropy, but many did not evaluate the extent of neuromuscular block. Besides, they did not inspect the impact of distinct degrees of neuromuscular blockade on spectral entropy under dissimilar saturations of isoflurane inhalation. Hence, this study has evaluated variant degrees of minimum alveolar concentration (MAC) to estimate the isoflurane concentration, along with various levels of neuromuscular blockade.

This study aims to evaluate the effect of muscle relaxants (atracurium and rocuronium) on entropy readings (state, response entropy, and response-state difference) during isoflurane anesthesia.

This is a prospective randomized study, as forty patients have been included and divided into two study groups: patients in group A received atracurium, while patients in group R received rocuronium. Under 50% and 100% neuromuscular blockage, state and response entropy were observed at MACs of 0.8% and 1%, respectively.

Results

There was a positive correlation between state (SE) and response entropy (RE) at baseline, different MACs, and different trains of four (TOF) for both atracurium and rocuronium. State and response entropy decreased with increasing MAC of isoflurane (P < 0.001), while atracurium and rocuronium at TOF 50% and 100% showed no effect on SE, RE, or RE-SE (P > 0.05).

Conclusions

State and response entropy can be used effectively to evaluate the depth of anesthesia at different isoflurane MAC and atracurium or rocuronium doses.

Registration number

ClinicalTrials.gov identifier: NCT 05097508, Registered October 5, 2021 (prospectively registered), http://www.ClinicalTrial.gov
Novel MTO1 mutations associated with an intrafamilial phenotypic variability
Authors: Almeida Catarina Maria , Rodrigues Esmeralda , Campos Teresa Almeida , Vilarinho Laura , Teles Elisa Leão
Published: January 2023

Background

Mitochondrial diseases are a group of rare inborn metabolic disorders with multi-systemic manifestations. MTO1 gene mutations are associated with MTO1 (Mitochondrial tRNA Translation Optimization 1) protein deficiency, a mitochondrial disorder, which commonly presents with lactic acidosis and hypertrophic cardiomyopathy.

Case presentation

The authors describe two siblings with mitochondrial cytopathy and distinct outcomes. The index case, a female born in 1989, presented hypotonia and lactic acidosis since birth. She developed a severe myoclonic encephalopathy, movement disorder and psychomotor and growth delay. Respiratory chain enzyme complex measurement in muscle revealed a partial deficiency of complex III and IV. Throughout the years she had multiple decompensations with severe acidemia and died at age of 16, due to a respiratory infection. She never presented cardiac alterations. The younger sibling, a male born in 2002, had a less severe clinical presentation. He presented hypotonia and lactic acidosis at birth. Metabolic study performed in the first days of life revealed elevated plasma alanine and hyperlactacidemia. At 8 months of age a partial deficiency of complex IV was reported. He had a mild persistent hyperlactacidemia, psychomotor development delay, generalized hypotonia, dilated cardiomyopathy and epilepsy. In 2017, at 15 years of age, a genetic study confirmed the mitochondrial disease with identification of two MTO1 likely pathogenic variants [c.413delT (p.M138Sfs*6) / c.1450C > T (p.R484W)]. Currently, he is clinically stable, maintaining a multidisciplinary follow up. The same genotype was confirmed in his sister’s stored DNA.

Conclusions

With this case, report the authors emphasize mitochondrial diseases' phenotypic heterogeneity, even in the same family, and the significance of the new genetic diagnostic techniques. The authors also report a novel MTO1 likely pathogenic variant not described to date.
Huge right ventricular myxoma in a 15-year-old female patient: a case report and literature review
Authors: Deebis Ahmed , Elattar Hala , Bakry Ahmed
Published: January 2023

Background

Myxomas represent about 5–10% of primary cardiac tumors in children, and only about 2.5–4% of cardiac myxomas originate from ventricular chambers. Symptoms and signs of right ventricular tumors depend mainly on the size and the site of the tumor and its effect on the inflow and outflow of the blood.

Case presentation

A 15-year-old female patient presented with syncope on exertion and symptoms and signs of congestive heart failure. She had a history of dyspnea and palpitation on exertion for 2 years before admission. Echocardiography and cardiac magnetic resonance imaging (MRI) diagnose a huge right ventricular mobile mass (9 × 4.6 × 3.7 cm) prolapsing during systole into the main pulmonary artery and severe tricuspid regurgitation. The mass showed no contrast enhancement in early dynamic and delayed gadolinium images, suggestive of a thrombus. The mass was safely excised and tricuspid annuloplasty repair was done using right atriotomy and vertical right ventriculotomy approaches. The patient was discharged in a well condition on postoperative day 6. Pathologically, the mass was confirmed as cardiac myxoma with old extensive hemorrhage inside.

Conclusions

Early echocardiography is essential for patients complaining of unexplained cardiac symptoms for early diagnosis and management of rare cases. Multimodality imaging is needed for the diagnosis and planning of the surgical procedure of right ventricular masses. Hemorrhage inside myxoma may lead to no contrast enhancement of the tumor.
Impact of the HLA Immunopeptidome on Survival of Leukemia Patients After Unrelated Donor Transplantation
Authors: Crivello Pietro , Arrieta-Bolaños Esteban , He Meilun , Wang Tao , Fingerson Stephanie , Gadalla Shahinaz M. , Paczesny Sophie , Marsh Steven G.E. , Lee Stephanie J. , Spellman Stephen R. , Bolon Yung-Tsi , Fleischhauer Katharina
Published: January 2023

PURPOSE

Immunopeptidome divergence between mismatched HLA-DP is a determinant of T-cell alloreactivity and clinical tolerability after fully HLA-A, -B, -C, -DRB1, -DQB1 matched unrelated donor hematopoietic cell transplantation (UD-HCT). Here, we tested this concept in HLA-A, -B, and -C disparities after single class I HLA-mismatched UD-HCT.

PATIENTS AND METHODS

We studied 2,391 single class I HLA-mismatched and 14,426 fully HLA-matched UD-HCT performed between 2008 and 2018 for acute leukemia or myelodysplastic syndromes. Hierarchical clustering of experimentally determined peptide-binding motifs (PBM) was used as a proxy for immunopeptidome divergence of HLA-A, -B, or -C disparities, allowing us to classify 1,629/2,391 (68.1%) of the HLA-mismatched UD-HCT as PBM-matched or PBM-mismatched. Risks associated with PBM-matching status were assessed by Cox proportional hazards models, with overall survival (OS) as the primary end point.

RESULTS

Relative to full matches, bidirectional or unidirectional PBM mismatches in graft-versus-host (GVH) direction (PBM-GVH mismatches, 60.7%) were associated with significantly lower OS (hazard ratio [HR], 1.48; P < .0001), while unidirectional PBM mismatches in host-versus-graft direction or PBM matches (PBM-GVH matches, 39.3%) were not (HR, 1.13; P = .1017). PBM-GVH mismatches also had significantly lower OS than PBM-GVH matches in direct comparison (HR, 1.32; P = .0036). The hazards for transplant-related mortality and acute and chronic graft-versus-host disease but not relapse increased stepwise from full HLA matches to single PBM-GVH matches, and single PBM-GVH mismatches. A webtool for PBM-matching of single class I HLA-mismatched donor-recipient pairs was developed.

CONCLUSION

PBM-GVH mismatches inform mortality risks after single class I HLA-mismatched UD-HCT, suggesting that prospective consideration of directional PBM-matching status might improve outcome. These findings highlight immunopeptidome divergence between mismatched HLA as a driver of clinical tolerability in UD-HCT.
Sartre accusateur de Baudelaire ?
Authors: Louette Jean-François
Published: January 2023

Une esquisse de biographie existentielle ; une esquisse de psychanalyse existentielle ; une esquisse d’éthique existentielle – voilà le Baudelaire de Sartre1. Ce n’est pas le moins du monde une charge contre Les Fleurs du Mal ou Le Spleen de Paris ni une étude des ces œuvres. Mais une thèse s’y trouve posée dès la fin du premier paragraphe : les hommes n’ont jamais que la vie qu’ils méritent, et Baudelaire n’échappe pas à la règle. Sartre n’aurait guère aimé notre époque où tout un chacun se proclame victime. Et il allait à contre-courant du grand mouvement de réhabilitation dont Baudelaire bénéficia depuis la fin du XIXe siècle. Peut-être Sartre fut-il le dernier accusateur de Baudelaire ? Mais en quel sens, au juste ? N’est-ce pas aussi avec lui-même qu’il cherche à régler ses comptes ? Tout en faisant de Baudelaire l’occasion d’une réflexion sur l’histoire littéraire de la poésie aux XIXe et XXe siècles.
Overdetermined: Psychoanalysis and Solidarity
Authors: Rada Michelle
Published: January 2023

With common unhappiness as its curative horizon, psychoanalysis deserves—indeed, it requires—the hysteric’s famous challenge to Freud: what, and whom, is analysis for? Motivated by the hysteric’s desire for a better life and Freud’s commitment to the social dimension of the psyche, this special issue considers psychoanalysis—theory and clinic—as the grounds for solidarity and political community, from the consulting room to the picket line. This extended introduction elaborates on the curative limitations and social dimensions of psychoanalysis by digging into a term—overdetermination—that has structured the psychoanalytic social bond from the origins of the talking cure. In putting the subject to grips with the disorienting effects of intersubjectivity, psychoanalysis constructs an ethical relation grounded in the illocutionary enactment of the subject’s negativity, sustaining a bond of care between divided subjects and between their overdetermined desires. This essay considers what the psychoanalytic commitment to our unhappiness in common might generate or foreclose for political bonds of solidarity beyond the consulting room.
No Touching: Boundary Violation and Analytic Solidarity
Authors: Zeavin Hannah
Published: January 2023

“No Touching” argues that we can locate analytic solidarity in the boundaries drawn to protect analytic work from sexual enactment. The author traces ongoing elaborations of the notions of boundary and boundary violation as they become codified across the twentieth century in American (ego psychology) psychoanalysis and its legal and training institutions, in parallel with the retheorization of transference love toward a stable notion of erotic transference. The author argues that professional psychoanalytic institutions and associations only began to legislate boundary violation as a normative ethics problem when the feminization of psychoanalysis took place in the 1970s through the 1990s. The author then turns to the “overbounding” of analysis in its teletherapeutic contexts to ask if psychoanalytic suspicions of mediation are in part based in their capacity to suspend traditional forms of boundary violation.
For Better or Worst: The Social Bond of Hysterics on Strike
Authors: Colston Alex
Published: January 2023

The social bond of the group or culture writ large, for both Freud and Lacan, is predicated on something that exceeds simple social convention, contract, or historical mode of production. This is evinced, for Freud, by his myth of the primal horde and his notion of how groups cohere through a vertical, fantasmatic identification with any given leader and their connection with the dead Father. For his part, Lacan generated his theory of the four discourses as a structural—and, indeed, more plausible—account of how social relations are impossible yet work nevertheless. He mapped these on the basis of what Freud called the impossible professions: education, governance, and psychoanalysis. For Lacan, these are what he calls discourses, particularly the university discourse (education), the master’s discourse (governing), the analyst’s discourse (psychoanalysis, transforming or revolutionizing), and, Lacan adds, the hysteric’s discourse (desiring and protesting). The latter’s innovative addition is what I explore in this paper: how the hysteric makes and breaks institutions with their desire by “going on a kind of strike.” The social bond, for Lacan, is demonstrated most dramatically by the hysteric on strike; as he says, “A strike is the most social thing there is in the whole world. It represents fabulous respect for the social bond.” Herein, I elucidate the discursive power of the hysteric’s social bond, and how it offers a more thoroughgoing way to think of horizontal solidarity as an alternative to Freud’s leader-led patriarchal civilization.
Soft Eyes in an Empty Box
Authors: Maxwell Jason
Published: January 2023

The article recounts the author's experiences designing an undergraduate business writing course that bridges the long-standing divide between the traditional liberal arts and professionally-oriented forms of education. This course, organized around the television series The Wire, helps students grapple with the interpretive complexities that shape contemporary institutional life.
Preparing for the Posthistorical University
Authors: Trivedi Amish
Published: January 2023

This article applies critical pedagogy to creative writing courses in the context of the modern transforming university. The author incorporates discussions of varied forms of capital, histories of cultural and capital production in the academy, and transforming canons into workshops to facilitate student contextualization of their own creative work.
Making Room for What We Read
Authors: Stratman Jacob
Published: January 2023

In a world of Google-age information accessibility and Facebook-fueled quick rants, the author is interested in teaching a process of reading poetry that does not include easily accessed “answers” or result in reactionary analysis. By using contemporary poetry in introduction to literature courses, the author invites students to resist any quick way of accessing information about the poem. Instead, using Billy Collins's poem, “Introduction to Poetry,” the author helps students explore slower, maybe more contemplative and welcoming ways to listen to the language of the poems they study. And, along the way, the author invites students to consider the particular intellectual virtues they are cultivating in order to read well. In this essay, the author uses Aimee Nezhukumatathil's poem “Hummingbird Abecedarian,” published through the Academy of American Poets Poem-a-Day project, and a poem the author had only read a couple of times before introducing to a group of second-semester first-year “Introduction to Literature” students, as an illustrative example of how using contemporary poems can deepen students’ reading experiences when there are no academic resources around to save them from taking time to read well.
What the Dickens
Authors: Huggins Sofia Prado , Henderson Kaylee
Published: January 2023

In this essay, the authors discuss how collaborative course design fundamentally reshapes power structures within the classroom, opening traditional texts and canonical authors to generative readings. Through the design of an introductory-level literature course centered around a single celebrity author, Charles Dickens, the co-teachers detail how students came to see authorship as an inherently collaborative act, and through the lens of Foucault's “author function,” how these students came to see themselves as both collaborators and authors. This course, from inception to execution, was a collaborative effort grounded in feminist pedagogy, and as demonstrated by student feedback and the project examples included in the appendix, this pedagogical approach empowered the students to recognize themselves as co-creators of knowledge within a classroom.
Ethnic Loyalty versus Spring Fancy
Authors: Stenberg Josh
Published: January 2023

Hei Ying 黑嬰 (1915–1992) wrote prolifically about the “southern isles,” where he—a Hakka from Sumatra—was born. Written for a sophisticated urban readership in China that was curious about the exotic and erotic Nanyang, Hei Ying's 1930s fiction foregrounds questions of Chinese ethnicity and nation. Ethnicity interacts with gender against sultry and desultory backgrounds, with improper patriotic or sexual tendencies attracting narrative punishment. Drawing on three pieces of his short fiction from the 1930s, this article argues that Hei Ying's theme of sexual temptation in the tropics rehearses European colonial (or Han majority) views of the impulsive, sultry native, an image that is contrasted with Republican Chinese primness. The bourgeois woman awakening to Chinese ethnonationalism and rejecting sensuality in favor of patriotism makes her an ancestor to the sexless heroines of Chinese revolutionary culture, including some Hei Ying would write later. The sensuality of the tropics thus operates as a foil for passions correctly channeled—toward nation (and eventually also party-state).
Scribble and E-cadherin cooperate to control symmetric daughter cell positioning by multiple mechanisms
Authors: Chann Anchi S. , Chen Ye , Kinwel Tanja , Humbert Patrick O. , Russell Sarah M.
Published: January 2023

The fate of the two daughter cells is intimately connected to their positioning, which is in turn regulated by cell junction remodelling and orientation of the mitotic spindle. How multiple cues are integrated to dictate the ultimate positioning of daughters is not clear. Here, we identify novel mechanisms of regulation of daughter positioning in single MCF10A cells. The polarity protein, Scribble cooperates with E-cadherin for sequential roles in daughter positioning. First Scribble stabilises E-cadherin at the mitotic cortex as well as the retraction fibres, to mediate spindle orientation. Second, Scribble re-locates to the junction between the two daughters to allow a new E-cadherin-based-interface to form between them, influencing the width of the nascent daughter–daughter junction and subsequent cell positioning. Thus, E-cadherin and Scribble dynamically relocate to different intracellular sites during cell division to orient the mitotic spindle and control placement of the daughter cells after cell division.

This article has an associated First Person interview with the first author of the paper.
Endosomal escape of RNA therapeutics: How do we solve this rate-limiting problem?
Authors: Dowdy Steven F.
Published: January 2023

With over 15 FDA approved drugs on the market and numerous ongoing clinical trials, RNA therapeutics, such as small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs), have shown great potential to treat human disease. Their mechanism of action is based entirely on the sequence of validated disease-causing genes without the prerequisite knowledge of protein structure, activity or cellular location. In contrast to small molecule therapeutics that passively diffuse across the cell membrane's lipid bilayer, RNA therapeutics are too large, too charged, and/or too hydrophilic to passively diffuse across the cellular membrane and instead are taken up into cells by endocytosis. However, endosomes are also composed of a lipid bilayer barrier that results in endosomal capture and retention of 99% of RNA therapeutics with 1% or less entering the cytoplasm. Although this very low level of endosomal escape has proven sufficient for liver and some CNS disorders, it is insufficient for the vast majority of extra-hepatic diseases. Unfortunately, there are currently no acceptable solutions to the endosomal escape problem. Consequently, before RNA therapeutics can be used to treat widespread human disease, the rate-limiting delivery problem of endosomal escape must be solved in a nontoxic manner.
Development of tailored splice-switching oligonucleotides for progressive brain disorders in Europe: development, regulation, and implementation considerations
Authors: Aartsma-Rus Annemieke , van Roon-Mom Willeke , Lauffer Marlen , Siezen Christine , Duijndam Britt , Coenen-de Roo Tineke , Schüle Rebecca , Synofzik Matthis , Graessner Holm
Published: January 2023

Splice-modulating antisense oligonucleotides (ASOs) offer treatment options for rare neurological diseases, including those with very rare mutations, where patient-specific, individualized ASOs have to be developed. Inspired by the development of milasen, the 1 Mutation 1 Medicine (1M1M) and Dutch Center for RNA Therapeutics (DCRT) aim to develop patient-specific ASOs and treat eligible patients within Europe and the Netherlands, respectively. Treatment will be provided under a named patient setting. Our initiatives benefited from regulatory advice from the European Medicines Agency (EMA) with regard to preclinical proof-of-concept studies, safety studies, compounding and measuring benefit and safety in treated patients. We here outline the most important considerations from these interactions and how we implemented this advice into our plan to develop and treat eligible patients within Europe.
Heritage and Tourism - In the age of digital transition and pandemic
Authors: Ronchi Alfredo
Published: January 2023

Digital transition together with all the related side effects plus the pandemic imposed a true stress test to tourism and cultural institutions. Extended lockdowns deeply impacted citizens’ lifestyle, significantly reducing social life and cultural enjoyment. Following the fil-rouge of the evolution of tourism in different forms up to overtourism impacting both residents and heritage. The paper explores the key indicators of overtourism and related causes. From the advent of models based on the number of visitors and the carrying capacity of tourist locations, to the most recent assessments which also consider visitor behaviour, time dimensions and concentration phenomena of people in certain places. The term overtourism is an umbrella that covers a wide range of causes including urban planning, infrastructures, city managers, different stakeholders, citizens and of course tourists and daily visitors. This to do not forget undertourism and its origins.
Early Hellenistic marble statue found in Alexandria, Egypt
Authors: Limneos Papakosta Calliope
Published: January 2023

On 4th of May 2009, in Shallalat Gardens of Alexandria, a marble statue was found, during the excavations held by H.R.I.A.C. (Hellenic Research Institute of Alexandrian Civilization). The statue represents a standing naked man in a form of classical contraposto, with one foot raised, possibly bent to a support. Head and body are in a very good condition, but the part of the legs under the knees is missing. The features of the statue, the attributes and the stylistic analysis are connected with the portraiture of Alexander the Great.
Epidemiology of pediatric schistosomiasis in hard-to-reach areas and populations: A scoping review protocol
Authors: Isaiah Phyllis Munyiva , Palmeirim Marta Sólveig , Steinmann Peter
Published: January 2023

Background: Schistosomiasis is a neglected tropical disease (NTD) that affects millions of people. Children are the most vulnerable group to developing overt disease. An estimated 779 million people are at risk of schistosomiasis and 50 million preschool-age children (PSAC) need treatment. PSAC are not currently targeted by national chemotherapy campaigns due to a lack of suitable pediatric formulations of praziquantel. The Pediatric Praziquantel Consortium has developed an orally dispersible praziquantel formulation (arpraziquantel) and is facilitating its adoption for schistosomiasis control by endemic countries through the ADOPT program – an implementation research program that paves the way for the large-scale delivery of the child-friendly formulation to treat schistosomiasis in preschool-aged children in endemic countries. A key challenge for comprehensive NTD control including schistosomiasis is reaching all at-risk populations, including those hard to reach. Main access barriers include geographic, social and economic conditions.

Objective: This scoping literature review aims to document the epidemiology of schistosomiasis in children under 6 years of age living in hard-to-reach areas and populations.

Methods: This review will adopt the five-stage scoping review process of identifying the research question, identifying relevant studies, study selection, charting data and collating, summarizing and reporting results. Electronic databases including Medline, Web of Science, Embase (Ovid), LILACS and African Journals OnLine (AJOL) will be searched for relevant articles. Two independent reviewers will screen identified articles using a two-stage approach of reviewing the title/abstract and then the full text of provisionally retained articles. Relevant literatures will be downloaded into EndNote X9 to maintain and manage citation and facilitate the overall review process. A meta-analysis will be conducted if indicated.

Relevance: The results will provide insights into the burden of schistosomiasis among marginalized PSAC, aiming to produce evidence on the need for inclusion of this population when designing the expansion of preventive chemotherapy programs.
Pragmatics in the context of English for occupational purposes: Speech acts produced by Japanese workers
Authors: Hijikata Yuko , Roberts Rachael D. , Ueno Masakazu
Published: January 2023

Background: Second-language (L2) pragmatics is one of the important fields of second-language acquisition research, where the native speakers’ norm is the standard. However, in another subfield of applied linguistics, English for occupational purposes (EOP), the importance of speakers’ expertise is instead emphasized. Although pragmatics plays an important role in workplace communication, few empirical studies examined Japanese workers’ English usage. This study clarifies how appropriately the participants can produce speech acts of request, apology, refusal, and advice-giving, and what factors affect their performances. Furthermore, we investigate the relationship between pragmatics scores and the strategies used by participants.  

Methods: We recruited 100 Japanese workers who speak English through a crowdsourcing platform. Complete responses from 92 participants were included in data analysis; eight people input the completion code but failed to save data on the survey response form, thus were excluded from the study. The participants answered demographic questions and then answered a written discourse completion task. We posed 12 situations, representing four speech acts: request, apology, refusal, and advice-giving. Considering the situation, the participants typed the English expression they would offer in response. Their responses were graded with a six-point rating rubric and coded using the strategy framework.

Results: Multiple strategies influenced the pragmatics scores, regardless of the type of speech act. Those who obtained higher scores tended to use multiple strategies, and not only main strategies but also modifications. The L2 proficiency was a significant factor affecting how participants offer an apology, while participants’ experiences of working abroad affected how they expressed refusal. Participants who obtained higher scores tended to use indirect pragmatics strategies, accompanied by modifications.

Conclusion: The application of multiple pragmatics strategies is essential, regardless of the speech act type. To extend the findings, further EOP research is required with a variety of transferred employees in inner/outer/expanding circles.
Model systems informing mechanisms and drug discovery: a systematic review of POLG-related disease models
Authors: Meyrick Jonathan , Stefanetti Renae J , Errington Linda , McFarland Robert , Gorman Gráinne S. , Lax Nichola Z.
Published: January 2023

Introduction

Pathogenic variants in the gene encoding the catalytic subunit of DNA polymerase gamma (POLG), comprise an important single-gene cause of inherited mitochondrial disorders. Clinical manifestations are now recognised as an array of overlapping clinical features rather than discrete syndromes as originally conceptualised. Animal and cellular models have been used to address numerous scientific questions, from basic science to the development and assessment of novel therapies. Here, we sought to perform a systematic review of the existing models used in mitochondrial research and their effectiveness in recapitulating POLG-related disease.

Methods

Four databases were searched from inception to May 31, 2022: MEDLINE, Scopus, Web of Science, and Cochrane Review. Original articles available in English, reporting the use of a model system designed to recapitulate POLG­-related disease, or related pathogenicity, were eligible for inclusion. Risk of bias and the methodological quality of articles were assessed by an adapted version of the Cochrane Risk of Bias Tool, with the quality of evidence synthesized across each model.

Results

A total of 55 articles, including seven model organisms (Human, yeast [Saccharomyces cerevisiae and Schizosaccharomyces pombe], Drosophila, Mouse, Nematoda, and Zebrafish) with 258 distinct variants were included. Of these, 66% (N=38) of articles recapitulated mitochondrial DNA (mtDNA) depletion and 42% (N=23) recapitulated POLG-related disease. Thirty-three percent of articles (N=18/55) utilised tissue-specific models of POLG-related dysfunction, while 13% (N=7) investigated the effect of potential therapeutics in POLG-related mitochondrial disorders.

Discussion

The available evidence supporting the ability of models for POLG-related disease to recapitulate molecular mechanisms and phenotype is limited, inconsistent and of poor methodologic quality.  Further success in examining and translating novel therapies into effective treatments will be enhanced by the availability of more robust models that better recapitulate the entire spectrum of POLG-related disease.

PROSPERO registration: CRD42021234883
Zinc for the Common Cold: Is It Worth a Try?
Authors: Sroczyńska Monika , Luchowska Anna , Żaczek Aleksandra
Published: January 2023

Introduction: Common cold is a viral infection of upper respiratory tract, caused by over 200 strains of viruses, mainly rhinoviruses, coronaviruses, adenoviruses and rotaviruses. The common cold is the most frequent infection among the human population and is responsible for up to 20% of all medical visits in developed countries. Despite this fact, no vaccine nor cure currrently exists. In recent years a number of studies have been published, describing effects of zinc supplementation on reduction of a duration of a common cold.
Aim of the study: A summary of the current state of knowledge, treatment efficacy and future possibilities regarding the use of zinc during the common cold.
Methods and materials: A review of the available literature on PubMed database, using keywords: „common cold”, „zinc supplementation”, „viral infection”
Results: Usage of zinc in appropriate dose during common cold leads to shortening the duration of an infection, as well as reducing severity of symptoms. Zinc supplementation has also a documented effect on decresing risk of viral infection.
Conculusions: Common cold, while being the most frequent viral infection among human population in developed world, leads to serious socioeconomic consequences. Therefore any aid in shortening the duration of this illness is much needed. Since zinc supplements have a documented positive effect on the speed of healing during acute viral infections and do not carry a significant number of side effects, they can be successfully used to treat the common cold.
Amantadine toxic effect and acute psychosis – a case report
Authors: Gruca Dariusz , Antoniak Krzysztof , Wais Marcin , Zając Marlena
Published: January 2023

Introduction and purpose: The pandemic of COVID-19 has induced patients to use different ways to struggle with SARS-CoV-2 infection. Amantadine has become more popular as a supportive drug in the treatment of COVID-19 symptoms. This report presents a case of a young, previously healthy woman hospitalized in the Toxicology and Cardiology Department because of acute psychosis induced by amantadine intoxication.
Brief description of the state of knowledge: Several medications, including psychostimulants, antibiotics, antivirals, and antiparkinsonians can cause acute psychosis. Amantadine has primarily dopaminergic with some anticholinergic properties and is used predominantly as an adjuvant agent in the management of Parkinson's disease treatment. Psychomotor agitation, insomnia, excessive verbosity, delusions, and behavioral disturbances are typical toxic effects of amantadine primarily affecting the central nervous system presented by the patient described in this case report.
Conclusions: Our case illustrates the adverse effects of amantadine on the central nervous system when given at the recommended dose to young, healthy women. Despite being rare, this induced psychosis may become more common, especially while becoming more popular as a supportive drug in COVID-19 treatment. While prescribing amantadine clinicians should be aware of the rapid onset of its psychotic complications.
Sexual activity in terms of cardiac rehabilitation after cardiovascular incidents
Authors: Grudzińska Aleksandra , Dudzińska Paulina , Milanowska Małgorzata , Jarosz Dominika , Tsitko Hanna
Published: January 2023

Cardiovascular diseases (CVD) are still the leading cause of death. Environmental factors such as smoking, low physical activity and poor diet have the greatest impact on the incidence of the disease. For patients after a cardiovascular incident, cardiac rehabilitation is the key to recovery. One possible path of rehabilitation is sexual activity (SA). Sexual activities are similar to mild/moderate physical activity during a short period. Most patients are recommended to involve in sexual activity after prior comprehensive evaluation of physical condition. Before involving in sexual activity the general condition of the patient needs to be checked.  A useful method for this is a stress testing. The patients with stable cardiac symptoms and good functional capacity are at a low risk of recurrent cardiovascular events, and others require treatment or improvement of heart function. The most efficient way to provide SA is a sexual counseling. Evidence suggests that relatively few cardiac patients receive sexual counseling, which can result in negative outcomes ranging from psychological, physical, and quality of life. Sexual problems and concerns are prevalent, including patient and partner fear of causing another heart attack. It is because people still believe that sexual activity is too risky and they cease all of it. Sexual counseling is needed across health care settings to ensure that patients receive information to safely resume SA.
Late-onset Pompe disease - literature review and summary of current knowledge
Authors: Jaskuła Karolina , Merkisz Konrad , Nemeczek Sylwia , Walczak Klaudia , Grzybowski Jakub , Marciniak Agnieszka , Orłowski Władysław , Grzywna Natalia , Walczak Patrycja , Salasa Weronika
Published: January 2023

Introduction: Pompe disease is a glycogen storage disorder caused by the deficient activity of the lysosomal enzyme acid α-glucosidase (GAA). Mutations in the GAA gene lead to the accumulation of glycogen in different organs. In a late-onset form (late-onset Pompe disease), the disease is characterized by slow, progressive proximal limb and respiratory muscle weakness. The diagnosis is based on a low level of GAA either in the muscle biopsy or in the leucocytes. LOPD is treated with enzyme replacement therapy (ERT).
Purpose: Summary of currently knowladge about Late-onset Pompe disease - characteristic, diagnosis and treatment.
Methods: A review of literature available in the PubMed database and Google Scholar. by searching for keywords: Pompe disease, Late-onset Pompe disease, LOPD, alglucosidase- α.
Results: The diagnosis of late-onset Pompe disease can often be difficult. It is a very rare disease and the clinical presentation is similar to other neuromuscular disorders, such as Duchenne and Backer muscular dystrophies, glycogenosis or autoimmune or mitochondrial myopathies and others. Despite available specific enzyme replacement therapy LOPD is progressive. Patients require support from a multidisciplinary team of specialists, including care from neurologists, pulmonologists or physiotherapists.
Conclusion: Although rare, Pompe disease should be considered in patients with proximal paresis and respiratory failure. More research into LOPD can help increasing precocity of diagnosis and treat it more effectively.
Adaptogens - use, history and future
Authors: Marciniak Agnieszka , Nemeczek Sylwia , Walczak Klaudia , Walczak Patrycja , Merkisz Konrad , Grzybowski Jakub , Grzywna Natalia , Jaskuła Karolina , Orłowski Władysław
Published: January 2023

Adaptogens are synthetic compounds or plant extracts that have the ability to increase the body's efficiency in the presence of stress stimuli. Extracts from ginseng, Eleutherococcus senticosus, Rhaponticum carthamoides, roseroot and chinensis are the best known plant adaptogens. The aim of this work is to assess the use of plant adaptogens in the past and present, and to outline the prospects for their future use. The use of natural adaptogens by humans has a rich history - they are used to treat many diseases, improve memory or reduce the effects of stress. Half a century ago, plant adaptogens were first used in competitive sports due to their effect on increasing the body's resistance to stress and improving physical endurance. Although many people now take plant adaptogens, human clinical trials are still very limited. Information obtained while writing this paper indicates that plant adaptogens may provide a number of benefits in the treatment of chronic fatigue, cognitive dysfunction and immune diseases.
Psoriasiform lesions as a side effect of SGLT-2 therapy
Authors: Gałązka Jakub Krzysztof , Domagalski Łukasz , Homa Piotr , Hoffman Zofia
Published: January 2023

SGLT-2 inhibitors (flozins) are one of the new classes of anti-diabetic drugs, used from 2012. They are highly recommended in case of intolerance or contraindication of metformin, but in Poland they are used usually as third-line drug after metformin and sulfonylurea. They growing popularity is caused by their significance in cardiovascular risk reduction and preventive role in according to diabetes complications like chronic kidney disease, or diabetes-induced dementia. The aid of this article is to summarize the knowledge on the risk of psoriasis development in diabetic patients cured with flozins.

            In according to the newest studies, flozins may be considered as a pro-psoriatic factor, increasing the risk of this skin disease, especially in patients with diabetic kidney disease. But on the other hand, SGLT-2 inhibitors have significantly decreasing effect on cardiovascular risk, which is increased in psoriatic patients.