bluuebunny/crossref_metadata_2025 huggingface dataset:
What motivates people with type 2 diabetes mellitus to participate in clinical trials from home?
Authors: Kopanz Julia , Lagerwaard Bart , Beran Magdalena , Veldwijk Jorien , Mader Julia K. , Pöttler Tina , Tews Dietrich , Grobbee Diederick E. , Zuidgeest Mira G. P. ,   the Trials@Home consortium
Published: November 2024

Decentralized clinical trials (DCTs), in which all or part of the trial activities are moved to the participants' immediate surroundings, promise to improve trial conduct. However, no evidence is available on what motivates people to participate in DCTs. Our aim was to determine the drivers and perceptions for participation in clinical trials with different decentralization levels in persons with type 2 diabetes mellitus. Five focus groups were conducted utilizing the nominal group technique in the Netherlands (n = 1), Germany (n = 1), and Austria (n = 3) with four to six participants per group. The focus groups were analyzed using thematic analysis. Of the 26 participants (10 females, median age: 66 years [IQR: 62–72]) 42% had previously participated in a trial, and almost all had internet access at home (96%). A total of seven main themes regarding participation in clinical trials (location, time investment, contact with healthcare professionals (HCPs), digital technologies, data collection, perceived risk, and motivation) were identified, of which a total of 20 drivers emerged. Perceptions regarding trial participation differed widely among participants, and individual preferences influenced which drivers were considered more important by participants. Flexibility of location and time spent on the trial were identified as the most motivating factors for participation in DCTs. Some drivers, such as digital infrastructure, digital literacy, home visits, personal interaction, and relationship with HCPs were perceived as both enablers and barriers, depending on personal preferences. However, most of the potential barriers regarding DCTs may be resolved by addressing them in the design of future DCTs.
Spatiotemporal Hotspots of Juvenile Bigeye and Yellowfin Tuna Catches Under Drifting Fish‐Aggregating Devices in the Eastern Atlantic Ocean to Define Moratorium Strata
Authors: Akia Sosthene Alban Valeryn , Guéry Loreleï , Pascual‐Alayón Pedro J. , Gaertner Daniel
Published: November 2024

To reduce catches of juvenile bigeye and yellowfin tuna, while maintaining skipjack catches under drifting fish aggregating devices (dFAD), we analyzed spatiotemporal distributions of dFAD catches by European purse seiners in the Eastern Atlantic Ocean during 1996–2019. To detect hotspots of juvenile dFAD catches, we: identified periods of maximum abundance using a seasonal sub‐series diagram; normalized monthly FAD catches per unit effort; and used emerging hotspots analysis on spatiotemporal density. Two main spatiotemporal strata were identified in the Guinean Gulf, which could be used to establish moratoria on dFAD fishing. These spatiotemporal strata differed from the existing ICCAT moratorium, which spanned a larger part of the African coast. Our findings also indicated that time‐area closures of dFAD‐fishing lasting 3–4 months in smaller areas could be more effective than the current dFAD moratorium to reduce unwanted bycatch in the Eastern Atlantic region. The two metrics we developed for comparison provided clear and measurable evidence that demonstrated how strategic and data‐informed moratoriums can lead to substantial improvements in conservation.
Occipital neuralgia as an initial manifestation of atypical Lemierre syndrome: A case report
Authors: Hanazono Akira , Yasuda Keita , Nagata Atsuyoshi , Kitamura Toshiharu , Sugawara Masashiro
Published: November 2024

Lemierre syndrome is a life‐threatening but treatable septic thrombosis of the internal jugular vein (IJV) derived from a craniocervical bacterial infection. Metastatic septic embolization is common. However, diagnostic delay and poor prognosis remain a problem, largely due to the diverse clinical presentations and unclear symptomatology of Lemierre syndrome. In contrast, occipital neuralgia is a common disease typically treated with symptomatic therapy in emergency settings, as most cases are not life‐threatening. The present case involved a 70‐year‐old female with Lemierre syndrome stemming from Streptococcus anginosus infection originating in sinusitis or periodontitis. The onset was characterized by headache with typical occipital neuralgia, a severe trigger point in the posterior neck ipsilateral to the infected IJV, and reduced sensation of the C2 nerve root area. Given the anatomical relationship of the cranial venous emissary system into the posterior cervical venous plexus, the case highlights the potential for the neighboring occipital nerve to be directly involved in Lemierre syndrome. Interestingly, despite Lemierre syndrome typically arising from pharyngeal bacterial infections and infected IJV located in the “anterior” neck, many prior case reports have described “occipital” or “posterior” pain at the head or neck. History taking and physical examination remain essential to identify the causes of these posterior/occipital symptoms, since imaging investigations, as in this case, often fail to identify them. Early recognition of occipital neuralgia as a potential initial symptom of Lemierre syndrome could lead to earlier diagnosis and treatment, potentially improving patient outcomes.
INHERITANCE AND INCEST: TOWARD A LÉVI‐STRAUSSIAN READING OF MONTESQUIEU'S DE L'ESPRIT DES LOIS1
Authors: Cheney Paul
Published: November 2024

The premise of this article is that Montesquieu, while seen as an Enlightenment thinker who contributed centrally to the development of the social sciences before the period of discipline formation in the nineteenth century, is generally appreciated in only the vaguest of terms. To the degree that he has been seen as a social theorist rather than as a belletrist or a political writer, scholars have had to amputate major sections of his masterwork, De l'esprit des lois (1748). In so doing, they have tended to give false or at least only partial readings of a work whose author insisted must be read as a whole. This article proceeds in an unorthodox fashion—at least for a historian—through a reading of De l'esprit des lois against Claude Lévi‐Strauss's Les structures élémentaires de la parenté (1949). Through this parallel reading, I establish that Montesquieu's treatment of inheritance bears a remarkable homology with Lévi‐Strauss's treatment of incest in Les structures élémentaires. These authors saw their respective objects—the incest taboo, in one case, and inheritance law, in the other—as fundamental to regulating sociability itself. This technique offers a more unified reading of De l'esprit des lois and, in so doing, reassesses Montesquieu's contribution to modern social theory. From a methodological point of view, I am hoping to interest my readers in an alternative way of reading historical texts: juxtaposing texts or corpora that do not have the clear genetic links between them that are generally highly valued by historians. This is an example of what Robert B. Pippin has called “interanimation” and what I have elsewhere likened to the painterly technique of simultaneous contrast.
The impact of land use on the acoustic behaviour of cicadas in the Chocó lowland tropical forest of Ecuador
Authors: Gindhart Rosa , Müller Jörg , Burivalova Zuzana , Blüthgen Nico , Busse Annika , de la Hoz Maria , Donoso David A. , Feldhaar Heike , Grella Nina , Kortmann Mareike , Kriegel Peter , Kümmet Sonja , Newell Felicity L. , Püls Marcel , Schaefer H. Martin , Seibold Sebastian , Tremlett Constance J. , Mitesser Oliver
Published: November 2024

The biodiversity of tropical rainforests is under extreme pressure due to the expansion of agricultural land. Beyond the immediate risk of species extinction, the intensification of land use can alter species' behaviour with consequences for the entire ecosystem.

In this study we investigated the impact of land use on the acoustic behaviour of cicadas in the highly biodiverse Ecuadorian Chocó region. We used passive acoustic monitoring (PAM) for the collection of audio data, from which we identified and analysed the sound activity of cicadas and the structure of daily patterns along a chronosequence of forest recovery. At landscape scale we studied the impact of a surrounding either dominated by agricultural land use or forests on the acoustic behaviour of cicadas.

Cicada sound activity was significantly lower in active agriculture compared to undisturbed old‐growth forest and increased along the forest recovery gradient. The diurnal pattern changed from simple in active agriculture to more complex and highly synchronized along the recovery gradient towards old‐growth forests. A surrounding dominated by agricultural land use additionally reduced the sound activity of cicadas and simplified the diurnal pattern in old‐growth forests.

Taken together, agricultural land use at local and landscape scales affects overall activity, diurnal patterns and synchrony of vocalizing song cicadas. This is a concerning trend considering the direct link between chorusing and fitness for cicadas. However, mature restoration forests embedded in forest dominated landscape surroundings showed restored cicada song behaviours similar to those of old‐growth forests, which underlines the conservation value of advanced secondary forests and the importance to support forest regeneration in the tropics.
Examining the Effects of the L2 Learning Experience on the Ideal L2 Self and Ought‐to L2 Self in a Japanese University Context
Authors: Huang Jerry , Mizumoto Atsushi , Bailey Benjamin
Published: November 2024

Dörnyei's L2 motivational self‐system (L2MSS) is a dominant theory within the field of language motivation research. In this study, we explore the interrelationship between the three central components of L2MSS, with a particular focus on the often‐overlooked L2 learning experience (L2LE). While previous research has primarily examined the Ideal L2 Self and Ought‐to L2 Self in relation to various factors, this paper explores the impact of the L2LE on these two motivational constructs. We collected and analyzed data from 238 surveys administered online to Japanese university students using structural equation modeling. The results indicate that the L2LE has a causal pathway toward both the Ideal L2 Self and Ought‐to L2 Self, characterized by a moderate to strong degree of influence. Furthermore, there exists a moderate to strong causal relationship between the Ideal L2 Self and the Ought‐to L2 Self. The results of this study should have clear implications for educators and researchers, as it shows the importance of the L2LE and should encourage further research into this still underexplored construct.
Effectiveness of Acceptance and Commitment Therapy on Reducing Depression and Anxiety in Older Adults: A Systematic Review and Meta‐Analysis
Authors: Sun Yali , Tian Zixiao , Ma Yongfang , Zhu Qiuyue , Zheng Ruichang , Guan Yan , Zhang Xiaojie
Published: November 2024

Objective

To assess the effectiveness of acceptance and commitment therapy (ACT) in reducing depressive and anxiety symptoms in older adults.

Design

A systematic review and meta‐analysis.

Methods

Nine databases were searched for publications up to 2 April 2024, using combinations of search terms related to depression, anxiety, ACT, older adults and randomised controlled trials (RCTs). Two researchers were selected according to inclusion and exclusion criteria, data extraction and methodological quality evaluation, and Stata 16.0 software was used for meta‐analysis.

Results

Seven articles were included in a systematic review and six were in a meta‐analysis. The results indicated that, compared to the control group, ACT had a small but significant effect in reducing depressive symptom (SMD = −0.22, 95% CI, −0.38 to −0.06, p < 0.001; 576 older adults; low‐quality evidence), while it showed a small, non‐significant effect on reducing anxiety symptoms (SMD = −0.29, 95% CI, −0.73 to 0.15, p = 0.194; 576 older adults; very low‐quality evidence). Subgroup analysis based on the different control conditions may have some enlightenment on the sources of heterogeneity.

Conclusion

ACT can be an important component of future psychotherapy for older adults, as it may alleviate depressive symptoms. However, high‐quality studies with large samples, multiple centres and long follow‐up durations should be performed to further reliably assess the treatment effects of depressive symptoms and explore potential benefits for anxiety symptoms.
MASLD, At‐Risk MASH and Increased Liver Stiffness Are Associated With Young Adulthood Obesity Without Residual Risk After Losing Obesity
Authors: van Kleef Laurens A. , Pustjens Jesse , Savas Mesut , Ayada Ibrahim , Li Pengfei , Pan Qiuwei , van Rossum Elisabeth F. C. , Janssen Harry L. A. , Brouwer Willem P.
Published: November 2024

Background

Obesity can result in persistent metabolic changes despite weight loss, which may affect liver health. We aimed to investigate associations between young adulthood obesity and metabolic dysfunction‐associated steatotic liver disease (MASLD), at‐risk steatohepatitis and increased liver stiffness measurement (LSM) in a general population setting.

Methods

We studied NHANES 2017–2020 community‐dwelling participants aged > 40 years with BMI ≥ 18.5 and no heart failure. Weight at age 25 was obtained through questionnaires and compared to current weight. Assessment included controlled attenuation parameter (CAP) and LSM. Associations between obesity status change with MASLD or at‐risk metabolic dysfunction‐associated steatohepatitis (MASH) and increased LSM were investigated and adjusted for demographics and metabolic health.

Results

The cohort comprised 4,580 participants (57% stable non‐obesity, 33% gained obesity, 2% lost obesity and 8% stable obesity). Compared to stable no‐obesity, stable obesity was strongly associated with MASLD (odds ratio [OR]: 5.47, 95% confidence interval [95%CI]: 3.97–7.66) as was gained obesity (OR: 4.68, 95% CI: 3.93–5.59), whereas no increased risk was demonstrated for lost obesity (OR: 1.26, 95% CI: 0.76–2.10). Similar associations for stable obesity and gained obesity with at‐risk MASH and LSM ≥ 8 kPa were demonstrated. No residual risk was found for lost obesity (MASH–OR: 1.05 95% CI: 0.36–2.49; LSM ≥ 8 kPa–OR: 0.85, 95% CI: 0.29–1.97). Results were consistent in sensitivity analysis where obesity change was calculated over the past 10 years and weight change was stratified in normal weight/overweight/obesity.

Conclusion

Young adulthood obesity is an important risk factor for MASLD, at‐risk MASH and increased LSM among the general population aged 40–80 years. Losing obesity resulted in normalisation of odds for MASLD, at‐risk MASH and increased LSM. These findings underline the importance of preventing and treating young adulthood obesity to maintain liver health.
Born high, born fast: Does highland birth confer a pulmonary advantage for sea level endurance?
Authors: Paris Hunter L. , Baranauskas Marissa N. , Constantini Keren , Shei Ren‐Jay , Allen Peyton E. , Jadovitz John R. , Wiggins Chad C. , Storm Cooker Perkins
Published: November 2024

Less than 7% of the world's population live at an altitude above 1500 m. Yet, as many as 67% of medalists in the 2020 men's and women's Olympic marathon, and 100% of medalists in the 2020 men's and women's Olympic 5000 m track race may have been born or raised above this otherwise rare threshold. As a possible explanation, research spanning nearly a quarter of a century demonstrates that indigenous highlanders exhibit pulmonary adaptations distinct from their lowland counterparts. These adaptations may then promote endurance performance. Indeed, healthy indigenous highlanders often exhibit a larger aerobic exercise capacity compared to sea‐level residents who travel to high altitude. However, questions remain on whether high‐altitude birth is advantageous for sea‐level competitions. In this review, we ask whether being born at a high altitude generates an ergogenic advantage for endurance performance in the Summer Olympics—a venue that is generally held at sea level. In so doing, we distinguish between three groups of high‐altitude residents: (i) the indigenous highlander, (ii) the highland newcomer, and (iii) the highland sojourner. Concentrating specifically on altitude‐induced alterations to pulmonary physiology beginning in the perinatal period, we propose that if altitude‐related maladaptations are avoided, genomic and developmental alterations accompanying highland birth may present benefits for endurance competitions at sea level.
Structural basis for the reaction cycle and transport mechanism of human Na
+
-sulfate cotransporter NaS1 (SLC13A1)
Authors: Chen Xudong , Zhang Youqi , Yin Jian , Liu Chang , Xie Min , Wang Yixue , Chen Meiying , Zhang Rui , Yuan Xinyi , Li De , Chen Xiangmei , Gao Xin , Cai Guangyan , Zhang Sensen , Zhou Boda , Yang Maojun
Published: November 2024

Sulfate (SO
4
2−
) is a pivotal inorganic anion with essential roles in mammalian physiology. NaS1, a member of solute carrier 13 family and divalent anion/sodium symporter family, functions as a Na
+
-sulfate cotransporter, facilitating sulfate (re)absorption across renal proximal tubule and small intestine epithelia. While previous studies have linked several human disorders to mutations in the
NaS1
gene, its transport mechanism remains unclear. Here, we report the cryo–electron microscopy structures of five distinct conformations of the human NaS1 at resolutions of 2.7 to 3.3 angstroms, revealing the substrates recognition mechanism and the conformational change of NaS1 during the Na
+
-sulfate cotransport cycle. Our studies delineate the molecular basis of the detailed dynamic transport cycle of NaS1. These findings advance the current understanding of the Na
+
-sulfate cotransport mechanism, human sulfate (re)absorption, and the implications of disease-associated NaS1 mutations.
Structural characterization and AlphaFold modeling of human T cell receptor recognition of NRAS cancer neoantigens
Authors: Wu Daichao , Yin Rui , Chen Guodong , Ribeiro-Filho Helder V. , Cheung Melyssa , Robbins Paul F. , Mariuzza Roy A. , Pierce Brian G.
Published: November 2024

T cell receptors (TCRs) that recognize cancer neoantigens are important for anticancer immune responses and immunotherapy. Understanding the structural basis of TCR recognition of neoantigens provides insights into their exquisite specificity and can enable design of optimized TCRs. We determined crystal structures of a human TCR in complex with NRAS Q61K and Q61R neoantigen peptides and HLA-A1 major histocompatibility complex (MHC), revealing the molecular underpinnings for dual recognition and specificity versus wild-type NRAS peptide. We then used multiple versions of AlphaFold to model the corresponding complex structures, given the challenge of immune recognition for such methods. One implementation of AlphaFold2 (TCRmodel2) with additional sampling was able to generate accurate models of the complexes, while AlphaFold3 also showed strong performance, although success was lower for other complexes. This study provides insights into TCR recognition of a shared cancer neoantigen as well as the utility and practical considerations for using AlphaFold to model TCR-peptide-MHC complexes.
Enhanced dual-mode imaging: Superior photoacoustic and ultrasound endoscopy in live pigs using a transparent ultrasound transducer
Authors: Kim Jaewoo , Heo Dasom , Cho Seonghee , Ha Mingyu , Park Jeongwoo , Ahn Joongho , Kim Minsu , Kim Donggyu , Jung Da Hyun , Kim Hyung Ham , Kim Hee Man , Kim Chulhong
Published: November 2024

Dual-mode photoacoustic/ultrasound endoscopy (ePAUS) is a promising tool for preclinical and clinical interventions. To be clinically useful, ePAUS must deliver high-performance ultrasound imaging comparable to commercial systems and maintain high photoacoustic imaging performance at long working distances. This requires a transducer with an intact physical aperture and coaxial alignment of acoustic and optical beams within the probe, a challenging integration task. We present a high-performance ePAUS probe with a miniaturized, optically transparent ultrasonic transducer (TUT) called ePAUS-TUT. The 1.8-mm-diameter probe, fitting into standard endoscopic channels, aligns acoustic and optical beams efficiently, achieving commercial-level ultrasound and high-resolution photoacoustic imaging over long distances. These imaging capabilities were validated through in vivo imaging of a rat’s rectum and a pig’s esophagus. The ePAUS-TUT system substantially enhances feasibility and potential for clinical applications.
Catalytic kinetic resolution of helical polycyclic phenols via an organocatalyzed enantioselective dearomative amination reaction
Authors: Chu Anqi , Zhu Boyan , Zhang Xiaoyong , Zhu Hanwen , Zhang Jingying , Liu Xihong
Published: November 2024

Despite the considerable potential applications for helically chiral molecules across various sectors, their catalytic asymmetric synthesis remains nascent and has seen very limited advancement compared to that of central and axial chiral compounds, primarily owing to the scarcity of available starting materials and the immense challenges associated with achieving stereochemical control. Herein, we report an innovative approach to the facile synthesis and catalytic kinetic resolution of uniquely structured and stereochemically complex helical polycyclic phenols by using a steric hindrance–regulated enantioselective dearomative amination reaction. The distinguished aspects of this method include the exceptional stability of the dearomatized products and impressive versatility of the recovered substrates in the construction of enantioenriched helical frameworks. This work showcases that the strategic incorporation of appropriate steric groups near the reaction site of an electron-rich aromatic compound can indeed enable an interrupted Friedel-Crafts reaction, thus opening an alternate avenue for the study of dearomatization in nonfunctionalized arenes.
Submillimeter fiber robots capable of decoupled macro-micro motion for endoluminal manipulation
Authors: Zhou Cheng , Xu Zheng , Lin Zecai , Qin Xiaotong , Xia Jingyuan , Ai Xiaojie , Lou Chuqian , Huang Ziyi , Huang Shaoping , Liu Huanghua , Zou Yun , Chen Weidong , Yang Guang-Zhong , Gao Anzhu
Published: November 2024

Endoluminal and endocavitary intervention via natural orifices of the body is an emerging trend in medicine, further underpinning the future of early intervention and precision surgery. This motivates the development of small continuum robots to navigate freely in confined and tortuous environment. The trade-off between a large range of motion and high precision with concomitant actuation cross-talk poses a major challenge. Here, we present a submillimeter-scale fiber robot (~1 mm) capable of decoupled macro and micro manipulations for intervention and operation. The thin optical fibers, working both as mechanical tendons and light waveguides, can be pulled/pushed to actuate the macro tendon-driven continuum robot and transmit light to actuate the liquid crystal elastomer–based micro built-in light-driven parallel robot. The combination of the decoupled macro and micro motions can accomplish accurate cross-scale motion from several millimeters down to tens of micrometers. In vivo animal studies are performed to demonstrate its positioning accuracy of precise micro operations in endoluminal or endocavitary intervention.
Reductive deaminative cross-coupling of alkyl bistriflimides enabled by electrocatalysis
Authors: Tao Xiangzhang , Lee Wooseok , Xu Zhimin , Shu Hui , Wang Qing , Ni Shengyang , Pan Yi , Hong Sungwoo , Wang Yi
Published: November 2024

We present a versatile nickel-electrocatalytic deaminative cross-coupling platform for the efficient construction of C(sp
3
)–C(sp
3
) and C(sp
3
)–C(sp
2
) bonds from readily available alkyl bistriflimides. This methodology involves the assembly of two leaving groups on alkyl amines to form alkyl bistriflimides, followed by their effective coupling with a wide range of alkyl halides, alkyl pseudohalides, aryl halides, and alkenyl halides under electrochemical reductive conditions. Moreover, the successful application of electrochemical reductive relay cross-coupling and transition metal–free cross-electrophile coupling further demonstrates the versatility of alkyl bistriflimides as valuable building blocks in organic synthesis. Combined control experiments and density functional theory calculations provide insights into the reaction pathway and the crucial role of iodide in the catalytic process.
Quantiles of Мmax and Other Characteristics of the Seismic Field Used in the Compilation of General Seismic Zoning (GSZ) Maps
Authors: Pisarenko V. F.
Published: November 2024

Abstract—A new probabilistic approach to the problem of estimating the regional maximum possible magnitude and some parameters of seismic impact is proposed. The methodology of its practical application is described, which is based on considering the maximum magnitude in the future time interval T as a random quantity and using its quantile with a given level of confidence as the regional maximum magnitude.
Developing a Congenital Upper Limb Difference Registry in Australia
Authors: WILKS Daniel James , MCCOMBE David B.
Published: November 2024

Clinical registries are increasingly common and have value in conditions such as congenital upper limb differences where collection of adequate data for scientific study can be challenging due to small numbers and clinical, surgical and psychosocial heterogeneity. This article discusses the motivation, purpose and development of the Australian Hand Differences Register before examining some of the challenges faced during its implementation and considering limitations of registry-derived data.

Level of Evidence: Level V (Diagnostic)
Analysis of a Data‐Driven Vector‐Borne Dengue Transmission Model for a Tropical Environment in Bangladesh
Authors: Al Mobin Mahadee , Kamrujjaman Md. , Molla Md. Mamun , Chen Shi
Published: November 2024

Dengue is the most prominent arboviral infection known to humans, especially in tropical regions of the world like Bangladesh. This is often a tricky outbreak to deal with, given its nature of seasonality, and due to the impact of climate change, variations in the length of its on‐season have been observed. This article models the dengue scenario in Bangladesh using a periodic, nonautonomous SIS vector–host model, proposes some development over the existing algorithm to determine the basic reproduction number, R0, for nonautonomous models, namely the “linear operator method,” and hence patriots the behavior of R0 with respect to the length of the on‐season. Our experimentation shows that the infection transmission will be at its peak when the length of the on‐season is around 10 months. Based on the data of 2022, the current dynamic of the disease scenario in Bangladesh shows that the disease will not persist in the long run but occasional outbreaks may occur, given the right set of conditions. Finally, we conduct a sensitivity analysis of the model parameters, which shows that improving the recovery rate of the infected patient class and impeding the birth rate of the vector can effectively subdue the disease outbreak.
Probabilistic Failure Risk Assessment of Aeroengine Disk Considering Manoeuvring Flight
Authors: Li Guo , Huang Shuchun , Lu Wanqiu , Zhou Huimin , Ding Shuiting
Published: November 2024

Accurately predicting the failure risk of aeroengine disks is a key part of engine safety design. The traditional probabilistic failure risk analysis framework has limitations in the selection of analysis time, risk characterization, and iteration criteria. These limitations restrict the applicability, efficiency, and accuracy of the traditional framework in analysing manoeuvring flights, especially for military aircraft. A new risk analysis framework was established to analyse the failure risk of a disk in manoeuvring flight. A centrifugal compressor disk was analysed during manoeuvring flight. The results showed that the failure risk considering the thermal–mechanical load of manoeuvring flight is approximately three times greater than the risk considering only the thermal–mechanical load at the most dangerous moments, which indicates the necessity of considering manoeuvring flight. This new analysis framework is verified to be superior to the traditional analysis framework in terms of convergence accuracy and efficiency. This work provides a reference for exploring probabilistic damage tolerance in complex environments, which is useful for aeroengine safety design.
Vitamin D Fortification: A Promising Approach to Overcome Drug Resistance and Tolerance in Therapeutic Interventions
Authors: Digvijaya  , Mittal Saurabh , Mittal Prateek , Singh Ruhi , Gupta Simran , Singh Taniya , Khan Rahmuddin , Alzobaidi Nafaa , Alhalmi Abdulsalam
Published: November 2024

The issue of drug resistance and tolerance presents a significant challenge as it diminishes the efficacy and potency of medications, posing a formidable obstacle for physicians striving to enhance pharmacological therapy worldwide. These resistance mechanisms can arise from genetic predispositions or as a consequence of medical interventions. Notably, acquired resistance or tolerance may extend to other drugs within the same or different classes, despite differing mechanisms of action. This phenomenon leads to the ineffectiveness of various pharmacological treatments over time, hindering the attainment of complete remission for numerous illnesses spanning metabolic disorders, autoimmune diseases, carcinomas, infectious diseases, cardiovascular diseases, and neurological disorders. Vitamin D, an essential lipid‐soluble nutrient crucial for regulating calcium and phosphorus levels, is emerging as a potential solution to counteract treatment resistance and tolerance in various conditions such as cancer, tuberculosis, and depression. This review scrutinizes existing research and offers insights for future investigations aimed at fully elucidating the therapeutic potential of vitamin D in mitigating the challenges associated with prolonged medication regimens and drug treatment failures.

Trial Registration: ClinicalTrials.gov identifier: NCT01169259 and NCT04342598.
Baicalein Long‐Circulating Liposomes Improve Histological and Functional Outcomes After Traumatic Brain Injury
Authors: Yuan Dong , Xu Wenbo , Raza Faisal , Zafar Hajra , Guan Shuangxian , Wang Zhen , Ullah Kamran Hidayat , Shi Hongchao
Published: November 2024

High mortality and disability have been principally linked with traumatic brain injury (TBI) with this condition being a principal issue in public health. Currently, there is no reliable pharmaceutical agent to salvage the damage caused by TBI. Baicalein (BCL), a traditional Chinese medicine active ingredient, has preliminarily shown repair activity on brain injury. However, BCL has poor water solubility and bioavailability, which culminates in rapid elimination in vivo. Herein, we sought to solve the above‐mentioned challenges that are associated with the application of this flavonoid by preparing BCL‐loaded long‐circulating liposomes (BLC‐Lips) via thin‐film hydration method. Subsequently, BLC‐Lips were applied to TBI model mice to evaluate their effect on brain injury repair. The results showed that the prepared BLC‐Lips exhibited smaller sized nanoparticles, excellent polydispersed index (PDI), and zeta (ζ)‐potential with stable property. After loading of BCL into the liposomes, we estimated the physicochemical properties of BLC‐Lips to be roughly 87.98% (encapsulation efficiency [EE]) and 7.56% (loading capacity of the drug). Administration of BLC‐Lips through oral route increased aqueous solubility, bioavailability, and time for in vivo circulation of BCL. Moreover, the BLC‐Lips could improve outcomes of histological and neurological motor function and reduce inflammatory cytokines and neurotoxicity after TBI. Taken together, the long‐circulating liposomes may serve as a new approach to potentially prolong drug circulation in vivo and increased bioavailability of BCL for TBI treatment.
TableS6 from ETx-22, a Novel Nectin-4–Directed Antibody–Drug Conjugate, Demonstrates Safety and Potent Antitumor Activity in Low-Nectin-4–Expressing Tumors
Authors: Lopez Marc , Crompot Emerence , Josselin Emmanuelle , Farina Anne , Rubis Marion , Castellano Remy , Fares Joanna , Wehbe Maria , Collette Yves , Charafe Emmanuelle , Blanchin Stéphanie , Romagne François , Pálfi Anikó , Hechler Torsten , Pahl Andreas , Azim Hatem A. , Lhospice Florence , Mamessier Emilie , Bertucci François , Elands Jack , Préville Xavier , Olive Daniel
Published: November 2024

Supplementary Table 6 shows the summary of GLP toxicology study results 
Table S4 from ETx-22, a Novel Nectin-4–Directed Antibody–Drug Conjugate, Demonstrates Safety and Potent Antitumor Activity in Low-Nectin-4–Expressing Tumors
Authors: Lopez Marc , Crompot Emerence , Josselin Emmanuelle , Farina Anne , Rubis Marion , Castellano Remy , Fares Joanna , Wehbe Maria , Collette Yves , Charafe Emmanuelle , Blanchin Stéphanie , Romagne François , Pálfi Anikó , Hechler Torsten , Pahl Andreas , Azim Hatem A. , Lhospice Florence , Mamessier Emilie , Bertucci François , Elands Jack , Préville Xavier , Olive Daniel
Published: November 2024

Supplementary Table 4 shows the PK data of ETx-22 in Cynomolgus monkeys
Table S1 from ETx-22, a Novel Nectin-4–Directed Antibody–Drug Conjugate, Demonstrates Safety and Potent Antitumor Activity in Low-Nectin-4–Expressing Tumors
Authors: Lopez Marc , Crompot Emerence , Josselin Emmanuelle , Farina Anne , Rubis Marion , Castellano Remy , Fares Joanna , Wehbe Maria , Collette Yves , Charafe Emmanuelle , Blanchin Stéphanie , Romagne François , Pálfi Anikó , Hechler Torsten , Pahl Andreas , Azim Hatem A. , Lhospice Florence , Mamessier Emilie , Bertucci François , Elands Jack , Préville Xavier , Olive Daniel
Published: November 2024

Supplementary Table 1 shows apparent affinity of various chimeric mAbs and human HA22 anti-nectin-4 mAbs
Figure S1 from ETx-22, a Novel Nectin-4–Directed Antibody–Drug Conjugate, Demonstrates Safety and Potent Antitumor Activity in Low-Nectin-4–Expressing Tumors
Authors: Lopez Marc , Crompot Emerence , Josselin Emmanuelle , Farina Anne , Rubis Marion , Castellano Remy , Fares Joanna , Wehbe Maria , Collette Yves , Charafe Emmanuelle , Blanchin Stéphanie , Romagne François , Pálfi Anikó , Hechler Torsten , Pahl Andreas , Azim Hatem A. , Lhospice Florence , Mamessier Emilie , Bertucci François , Elands Jack , Préville Xavier , Olive Daniel
Published: November 2024

Supplementary Figure 1 shows epitope mapping of humanized 15A7.5 to human nectin-4
Histology of Myopic Dome-Shaped Macula
Authors: Panda-Jonas Songhomitra , Jonas Jost B. , Jonas Shefali B. , Jonas Rahul A.
Published: November 2024

Introduction: The aim of the study was to examine the histological correlate of a dome-shaped macula in highly myopic human eyes. Case Presentation: We examined histomorphometrically the histological section of an enucleated, axially extremely elongated globe (axial length: 32.0 mm) of a Caucasian patient aged 56 years. The histological slide exhibited in the foveal region a localized scleral thickening up to 535 µm as compared to a scleral thickness of 298 µm and 310 µm in the parafoveal region. The choroid was thicker in the fovea than parafoveally (21 µm vs. 15 µm). Bruch’s membrane (BM) had a foveal defect (length: 19 µm), at one end of which BM was corrugated. The BM defect was spatially correlated with a subretinal proliferation of retinal pigment epithelium (RPE) cells. Within this subretinal fibrous mass, the RPE cells were connected with a PAS (periodic-acid-Schiff)-positive basal membrane. In the direction of the optic nerve head, BM ended at a distance of 3.8 mm from the optic disc, indicating a large parapapillary gamma zone. The BM end in direction to the optic disc showed a BM corrugation, suggesting a rupture of the lengthened and thinned choroidal peripapillary border tissue. Within parapapillary gamma zone, the peripapillary scleral flange (parapapillary delta zone) was elongated to a length of 0.42 mm and thinned to 94 µm. Conclusions: These histomorphometric findings agree with clinical, optical coherence tomography-based observations of eyes with DSMs, confirm the association of DSMs with macular BM defects, and support the notion of BM playing a role in the biomechanics of the eye.
Ecthyma Gangrenosum of Fungal Origin: A Case Report
Authors: León-Sánchez Germán Andrés , Lozada-Ramos Heiler , Daza-Arana Jorge Enrique , Restrepo-Becerra Andrés Darío , Varela-Miranda Ruben
Published: November 2024

Introduction: Ecthyma gangrenosum (EG) is usually a dermatologic manifestation of a Pseudomonas aeruginosa infection in an immunocompromised individual but may sometimes be caused by other bacteria or fungi in an immunocompromised or non-immunocompromised individual. Case Presentation: A 75-year-old woman with a history of high blood pressure and sequels of ischemic cerebral infarction presented with a 5-day history of general malaise, cough with yellow sputum, and respiratory distress. The patient had pale mucous membranes, temperature of 38.5°C, tachycardia, normal blood pressure, SaO2 of 85%, intercostal retractions, and severe bronchospasm upon hospital admission. No skin lesions were seen. The patient was admitted to the intensive care unit (ICU) because of her critical condition and was supported with invasive mechanical ventilation. Her blood count showed 8,100 leukocytes/mm3, neutrophils 79%, hemoglobin 10.1 g/dL, creatinine 1.1 mg/dL, and C-reactive protein 328 mg/dL. Arterial blood gases showed metabolic acidosis and moderate hypoxemia. The initial report of blood and urine cultures was negative for bacteria, and positive for influenza A H1N1. The patient was treated with oseltamivir and intravenous methylprednisolone for acute respiratory distress syndrome associated with the viral infection that occurred. Subsequently, violaceus macular and papular lesions appeared, which evolved into ulcerated lesions with erythematous border and necrotic center were seen in the anterior region of the chest and abdomen, from where Candida metapsilosis was isolated. EG was reported in this patient, who was also immunocompromised because of steroid use, had a prolonged stay in the ICU and received broad-spectrum antibiotics. Fungemia and urinary infection due to different fungi were also found. Conclusion: It is worth mentioning that EG can be caused by germs other than P. aeruginosa and fungal infections should not be ruled out.
The first reported case of Peroral Endoscopic Myotomy in a child in Portugal
Authors: Rodrigues Inês , Rodrigues Luís , Lopes Ana I. , Correia Luís , Moura Miguel
Published: November 2024

Introduction: Achalasia is a rare disorder, with few cases occurring during childhood. It is also part of the Allgrove syndrome phenotype and a clinical feature that has a major impact on children’s development. Timely diagnosis and effective treatment of symptoms are essential. The novel peroral endoscopic myotomy (POEM) may represent an effective alternative in children.
Case Presentation: We present the case of a female child born in 2013, without relevant family history or perinatal events. At six years old she presented with seizures related to recurrent hypoglycemia episodes and adrenal insufficiency was diagnosed. Two years later, the patient was referred to our institution due to regurgitation and vomiting, causing failure to thrive. After an upper endoscopy with no significant findings, high-resolution manometry revealed type II achalasia. Alacrimia was also part of the clinical picture and Allgrove syndrome was genetically confirmed. Due to significant symptoms, an endoscopic pneumatic dilation was performed, with transient relief of symptoms. After a second pneumatic dilation and several hospitalizations due to achalasia complications, a POEM was considered. She underwent POEM in March 2024, without adverse events and excellent short term outcomes.
Discussion: Although there is limited literature on POEM in children, the results demonstrate an encouraging success rate, compared to pneumatic dilation and laparoscopic Heller’s miotomy. We present the first reported case of POEM performed in a child in Portugal. The long-term efficacy of this promising minimally invasive procedure should be assessed in the pediatric population.
Sombras do grotesco: violência e horror em O Senhor das Moscas, de William Golding
Authors: Brandão Geysa Russielly Campelo , Sá Paula Fabrisia
Published: November 2024

This paper article to analyze the representation of the grotesque in The Lord of the Flies, by William Golding, since this work represents, through the presence of shocking expressions and plot, situations of conflict between conventional social laws and the creation of a new world, a familiar but strange one. Thus, first we are going to show the trajectory of this grotesque as a concept, this would take in to consideration the changes and variations and its meaning through the ages. In the second moment, we will discuss the grotesque world in the work under study, exploring how the rupture of childhood produces a violent and horrific scenario in the narrative, as well as the metaphors that symbolize the grotesque and the grotesque language of the work. In this study directed for this purpose, research was conducted from theories and studies of Kayser (2013), Hugo (2014), Bakhtin (2010) and Sodré and Paiva (2014). With this work, it is possible to verify that the grotesque is in all narratological aspects of The Lord of the Flies, leading the reader to reflect on human nature, fears, horrors and violence that surround us.
A metonímia horrífica na ficção: a concepção sui generis de monstros em "Consciência tranquila", de Cruz e Sousa
Authors: Santos Gabriel Costa Resende Pinto Bastos dos
Published: November 2024

This paper discusses a particular strategy of horror literature to conceive its monstruous characters: the horrific metonymy (CARROLL, 1999). After surveying possible representational shapes of the fictional monstrous, we decided to utilize this specific mode of the horrific metonymy, the most appropriate for our case, to critically analyze a short story by author João da Cruz e Sousa, well-known for being one of the arcanes of brazilian simbolism, about a cruel slave owner and the many horrors he sponsored. Without significantly diverging from a consolidated understanding of the “monster” classical category, our aim is to exemplify one of the ways of featuring the monstruous in brazilian literature, in which it has always to be furtively expressed in order to avoid the yoke of a critical and historiographical tradition that knowningly valorizes realistic and “documentary” criterions.
O Pio da Coruja: elementos góticos em S. Bernardo, de Graciliano Ramos
Authors: Maia Mateus de Novaes
Published: November 2024

This article aims to investigate the traces of a Gothic discourse in S. Bernardo (1934) by Graciliano Ramos. The analysis is conducted by identifying conventional elements of the Gothic tradition present in the novel — such as the locus horribilis, the monstrous character, and the ghostly presence of the past. Although the novel does not conform to a typically Gothic narrative, it is understood that the Gothic poetics permeating the text is operationalized according to the conventions of this tradition, expressing the anxieties of the narrator-protagonist regarding modernity and the decline of the rural patriarchal figure that shapes the foundation of the drama unfolding in the pages of the book, particularly in Chapter XIX. Additionally, parallels are drawn between the use of Gothic discourse in Graciliano Ramos's work and that of another author often associated with him, William Faulkner, through a comparative analysis with the novel Absalom, Absalom! (1936). Finally, a discussion is proposed regarding the possibility of situating S. Bernardo within attempts to categorize Brazilian Gothic.
Cores muito vivas
Authors: Oliveira Francisco
Published: November 2024

Literatura.
Racial and Ethnic Disparities in the Use and Outcomes With WATCHMAN FLX: A SURPASS Analysis of the NCDR Left Atrial Appendage Occlusion Registry
Authors: Alli Oluseun O. , Garg Jalaj , Boursiquot Brian C. , Kapadia Samir R. , Yeh Robert W. , Price Matthew J. , Piccini Jonathan P. , Nair Devi G. , Hsu Jonathan C. , Gibson Douglas N. , Allocco Dominic , Christen Thomas , Sutton Brad , Freeman James V.
Published: November 2024

Background

Left atrial appendage occlusion (LAAO) is increasingly used as an alternative to oral anticoagulation for stroke prevention in select patients with atrial fibrillation. Data on outcomes in racial and ethnic minority individuals are limited. This analysis assessed differences in the use and outcomes of LAAO by race and ethnicity in a large national registry.

Methods and Results

This analysis acquired data on patients who underwent WATCHMAN FLX implantation from the retrospective NCDR (National Cardiovascular Data Registry) LAAO registry through September 2022. All patients with an attempted WATCHMAN FLX implantation and known race and ethnicity were included. Baseline characteristics and 1‐year event rates were compared. A total of 97 185 patients were analyzed; 87 339 were White individuals (90%), 3750 Black individuals (3.9%), and 2866 Hispanic individuals (Hispanic/Latinx), 2.9%). Black and Hispanic patients were younger, with a higher incidence of prior stroke and significant bleeding compared with White patients. Black and Hispanic patients were treated with LAAO in smaller numbers relative to their proportion of the US population. Rates of procedural success were similar between groups. Though direct oral anticoagulants were prescribed in most patients across the groups, dual and single antiplatelet therapy were prescribed more often in Black patients. Black patients had significantly higher rates of 1‐year death and bleeding compared with White and Hispanic patients.

Conclusions

Patients from racial and ethnic minority groups comprise a disproportionately small fraction of all patients who undergo LAAO. Black and Hispanic patients were younger but had significantly higher comorbidities compared with White patients. Procedural success was similar among the groups, but Black patients experienced higher rates of death and bleeding at 1 year.