bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrogen enhances the proliferation, migration, and invasion of papillary thyroid carcinoma via the ERα/KRT19 signaling axis
Authors: Song Z. M. , Wang Y. D. , Chai F. , Zhang J. , Lv S. , Wang J. X. , Xi Y.
Published: October 2024

Background

Estrogen is thought to be the reason for the higher prevalence of papillary thyroid carcinoma (PTC) in fertile women; however, more study is required to completely comprehend how estrogen affects PTC development at the cellular level. Therefore, we combined Oxford Nanopore Technologies (ONT) sequencing to explore molecular markers of PTC and to investigate the molecular mechanisms by which estrogen promotes PTC development.

Methods

The expression levels of ESR1 (ERα) and KRT19 in normal thyroid tissues and cancer tissues as well as in different cancer stages, races, genders, age groups, histological subtypes and nodular metastasis status of the TCGA database were analyzed online by Ualcan; the relationship between ESR1, KRT19 and the survival of THCA patients was analyzed. A PTC xenograft tumor model was established. An ERα specific inhibitor (MPP) was administered and an EDU cell proliferation assay was used to verify the effect of estrogen on PTC proliferation. KRT19 was knocked down in KTC-1 cells, and the proliferation, migration, and invasion abilities of PTC cells were determined using CCK-8, immunofluorescence labeling, Western blot for EMT-related proteins, scratch assay, and Transwell assay. The role of ERα in relation to KRT19 was investigated by Western blot and immunofluorescence. The effects of ERα/KRT19 signaling axis on the proliferation, migration and invasion ability of PTC cells were evaluated using EDU cell proliferation assay and Transwell. Using ONT sequencing, 15 pairs of PTC tissue and paracancer tissue samples were collected. A PPI network was constructed to validate the differential expression of KRT19 in combination with biosignature analysis, and the protein interaction between KRT19 and ESR1 was verified using STRING.

Results

Ualcan showed that the expression of ESR1 and KRT19 was higher in THCA tissues than in normal thyroid tissues. E2 activation of ERα promoted the growth of PTC cells and tissues. si-KRT19 inhibited the proliferation, migration and invasion of PTC cells. KRT19 together with ERα formed the ERα/KRT19 signaling axis. E2 activation of the ERα/KRT19 signaling axis promoted the proliferation, migration, and invasion of PTC cells. ONT sequencing and STRING website verified that KRT19 is significantly differentially expressed in PTC and that ESR1 and KRT19 have protein interactions and are related to the estrogen signaling pathway.

Conclusions

Using public databases, RNA sequencing, and bioinformatics, we discovered that E2 stimulates the ERα/KRT19 signaling axis to stimulate PTC proliferation, migration, and invasion.
Teaching the Basics Brilliantly or Reinforcing Yet Another Subject Hierarchy?
Authors: Wrathall Jade
Published: October 2024

The New Zealand Curriculum is comprised of eight compulsory learning areas: English, the arts, health and physical education, learning languages, mathematics and statistics, science, social sciences, and technology. Collectively, these learning areas are intended to provide children with a broad and balanced education. Despite this, the National-led government have introduced a new education policy titled Teaching the Basics Brilliantly. As this policy is focused exclusively on reading, writing, mathematics, and science, a hierarchy of subjects will likely be reinforced. This article examines the different aspects of the Teaching the Basics Brilliantly policy and discusses the implications of privileging three of the eight learning areas.
‘The Little Things’: The Temporality of Young People’s Strategies for Existential, Grounded, and Expansive Wellbeing in Rural Australia
Authors: Lee Meghan
Published: October 2024

This paper is based on research in rural southeast Australia with young people from recent migrant and refugee backgrounds. While existing research on the wellbeing of this group often emphasises successful settlement through education, employment, and belonging as pathways to future wellbeing, this paper asks what we can learn from young people’s own experiences and understandings of wellbeing. Guided by the words, images, and reflections of young people involved in this research, the paper explores everyday wellbeing as an existential, relational, and situated happening that takes both time and place. Young people in the study highlighted the importance of finding beauty, joy, and connection in ‘the little things’ of daily life to bring a sense of meaning into monotonous temporal rhythms and weekly routines structured by work and study. Drawing from Todres and Galvin’s ‘dwelling-mobility’ wellbeing framework, this paper conceptualises young people’s ability to be well as intricately intertwined with their ability to experience their lives over time as grounded and secure, while also having a sense of greater meaning and possibility. Ultimately, the paper illustrates how young people understand their ability to be well as temporally complex, informed by ongoing, non-linear interactions between past, present, and future experiences as they look forward and back over their lives, seeking to transform the passage of time from meaningless to meaningful.
Waste 4.0: transforming medical waste management through digitalization and automated segregation
Authors: Mohamed Nurul Hamizah , Khan Samir , Jagtap Sandeep
Published: October 2024

Medical waste management is a crucial issue due to its potential health risks to humans and harm to the environment. The World Health Organization (WHO) advises separating medical waste into seven groups based on its type. However, despite the implementation of color-coded bin bags, cases of missegregation still occur frequently, leading to injuries and spreading diseases. Infectious waste such as sharps, human tissue, and body parts are often found mixed in waste bins, posing a severe threat to waste employees. To address this issue, this paper proposes exploring the potential of digitalization in waste segregation. The literature on current segregation methods and technology applications is analysed and compared, and a framework for utilizing barcode tagging and scanning to ensure waste is correctly categorized is presented. The barcodes and scanner will be connected through a monitoring system, which can notify waste generators and collectors of misplacing or mixed waste. This digitalization system is expected to serve as a monitoring agent for segregating waste before it is collected from any health facilities. Additionally, the exchanged data from waste generator bins can inform collectors and other waste stakeholders about the waste's condition, potentially opening up opportunities for recycling companies to purchase used plastics or metals from hospital wastes. By implementing digitalization in medical waste management, waste segregation can improve, reduce the spread of diseases and injuries, and promote the recycling of hospital waste materials.
Competing few-body correlations in ultracold Fermi polarons
Authors: Liu Ruijin , Cui Xiaoling
Published: October 2024

Polaron, a typical quasi-particle that describes a single impurity dressed with surrounding environment, serves as an ideal platform for bridging few- and many-body physics. In particular, different few-body correlations can compete with each other and lead to many intriguing phenomena. In this work, we review the recent progresses made in understanding few-body correlation effects in attractive Fermi polarons of ultracold gases. By adopting a unified variational ansatz that incorporates different few-body correlations in a single framework, we will discuss their competing effects in Fermi polarons when the impurity and majority fermions have the same or different masses. For the equal-mass case, we review the nature of polaron-molecule transition that is driven by two-body correlations, and especially highlight the finite momentum character and huge degeneracy of molecule states. For the mass-imbalanced case, we focus on the smooth crossover between polaron and various dressed clusters that originate from high-order correlations. These competing few-body correlations reviewed in Fermi polarons suggest a variety of exotic new phases in the corresponding many-body system of Fermi-Fermi mixtures.
Making sense of the interaction between geopolitics and middle-technology trap: evidence from China’s catching-up CNC machine tool industry
Authors: Yuan Haoyan
Published: October 2024

This study proposes a framework to analyze the interaction between geopolitics and the Middle-Technology Trap, drawing on evidence from China's CNC machine-tool industry. Qualitative methods such as interviews have been utilized to identify geopolitical variables that have driven the development of the Chinese CNC machine tools industry. To explore the combined effects of the Middle-Technology Trap and the intense competition between China and the West, this article focuses on an industry that has been significantly influenced by the economic decoupling between China and the US, a phenomenon deeply rooted in recent great power competition. While several industries may illustrate the new status quo of the Middle-Technology Trap, the CNC machine-tool industry is particularly exemplary due to its close interrelation with geopolitics. Accordingly, this study presents a catch-up case that incorporates technology-oriented aspects and factors from strategic competition, underlining three scenarios that geopolitics could influence the result of addresing the Middle-Technology Trap, respectively technological decoupling, the relocation of supply chain, and industrial policy.
The Neuropsychology of Dementia
Authors: Gerhand Simon
Published: October 2024

An up-to-date clinical guide for healthcare professionals on the assessment, diagnosis and management of dementia and mild cognitive impairment (MCI), including the role played by neuropsychology in the diagnostic process. Written in an accessible style, it provides a reference book for qualified professionals and a valuable resource for students and trainees working in dementia services. The book covers the diagnosis and management of the most common forms of dementia, and some rarer types, and the latest advances in diagnostic technology and current and future treatment options. It explores non-pharmacological interventions for cognitive impairment and preventative measures to reduce the risk of developing dementia. Featuring the essential background information required by all clinicians working in the field, alongside a review of recent research and developments in the field. With an emphasis on the links between theory and practice, this is a must-read manual for clinicians working in memory clinics.
Remedies in Australian Private Law
Authors: Barnett Katy , Harder Sirko
Published: October 2024

Remedies in Australian Private Law presents a detailed and scholarly map of remedies under Australian private law. Clearly structured and accessibly written, the text takes a black-letter law approach to remedies in common law, equity and statute, and develops a framework for understanding the principles of private law remedies and their practical application. The third edition has been updated to include recent cases in remedial law, offering students clear links between principles and practice, and provides more in-depth coverage of compensation under the Australian Consumer Law. Reasonable fee awards and disgorgement and accounts of profit are now addressed in separate chapters to reflect recent changes in international case law. Written by an expert author team, Remedies in Australian Private Law enables students and practitioners to develop a coherent understanding of remedial law and to analyse legal problems and identify appropriate remedial solutions.
Playing with Fire
Authors: Malik Aditi
Published: October 2024

Drawing on a rare cross-regional comparison of Kenya and India, Playing with Fire develops a novel explanation about ethnic party violence. Combining rich historical, qualitative, and quantitative data, the book demonstrates how levels of party instability can crucially inform the decisions of political elites to organize or support violence. Centrally, it shows that settings marked by unstable parties are more vulnerable to experiencing recurring and major episodes of party violence than those populated by durable parties. This is because transient parties enable politicians to disregard voters' future negative reactions to conflict. By contrast, stable party organizations compel politicians to take such costs into account, thereby dampening the potential for recurring and severe party violence. By centering political parties as key actors in the production of conflict, and bringing together evidence from both Africa and South Asia, Playing with Fire contributes new insights to the study of political violence.
Ireland's abstract review and the Judicial Appointments Commission Bill case
Authors: Cahillane Laura
Published: October 2024

The Irish Constitution contains a pre-enactment abstract review procedure under Article 26 whereby, before signing a Bill into law, the President can refer the Bill to the Supreme Court for a decision on its constitutionality. However, only 16 such references have ever been made. The reason Irish Presidents have been cautious about sending Bills to the Supreme Court for abstract review relates to the fact that if a Bill survives the Article 26 review process, it then acquires an immunity from further challenge under Article 34.3.3. This has sometimes been referred to as a ‘seal of constitutionality’ and the absolute nature of this blanket immunity has been criticised because it means that, in practice, the review process is rarely used. By its very nature, abstract review suffers from the defect that the provisions are being looked at in a vacuum, without the benefit of a concrete factual scenario and it may be that circumstances later arise which could result in an unconstitutionality that was not apparent when the Bill was initially examined. For this reason, Presidents will sometimes decide not to refer a Bill, even one which is considered controversial, for fear of closing off the Bill to potential future challenges; they may feel it is better for challenges to occur organically as situations arise rather than to prevent a situation where a future challenge is blocked by the immunity following the review process. As Hogan has put it, ‘[w]ithout a plaintiff, a court may fail to anticipate side-effects or unintended consequences of the law’. The paucity of occurrences means that when the procedure is invoked, there is a great interest (amongst members of the legal and academic communities at least) in the process and outcome.
God and Purported Logical Arguments from Evil and Suffering
Authors: Sterba James P.
Published: October 2024

Logical arguments from evil against the existence of God are the strongest form of arguments from evil. They maintain that the all-good, all-powerful God of traditional theism is logically incompatible with the evil in the world. Given that the most well-known logical argument from evil remains the argument put forward by John Mackie over fifty years ago, I begin by setting out Mackie’s argument in detail as well as Alvin Plantinga’s well-regarded critique of it. I then discuss Mackie’s not well-known confusing response to Plantinga’s critique along with attempts by Hugh LaFollette and Quentin Smith to support Mackie’s argument, which fail to take into account Mackie’s own concession to Plantinga’s critique. I then discuss my own attempt in 2019 to provide a Mackie-style logical argument from evil and the reception it has received. I end by suggesting that further discussion might best be pursued by taking up the related question of whether an objective ethics can by adequately supported without appealing to the existence of the God of traditional theism.
Sinicizing China’s World Muslim City: Spatial Politics, National Narratives, and Ethnoreligious Assimilation in the PRC
Authors: McCarthy Susan K.
Published: October 2024

The nation-state is as much a narrative and ideational project as it is a spatial-territorial one. In the People’s Republic of China, Xi Jinping’s calls to “revitalize” China’s traditional culture, “Sinicize” religions, and “rejuvenate” the Chinese nation reflect a broader effort to reframe the national narrative and strengthen Communist Party control. This article examines the implications of Xi’s revisionist nationalism for China’s fifty-five minority nationalities, in particular the Hui, one of ten Muslim minority groups. It does so by analyzing the rise and demise of World Muslim City (WMC), a development project in western China that mobilized Hui identity and traditions for economic and diplomatic purposes. WMC was facilitated by a multicultural national narrative and by a fragmented authoritarian political system that for many years fostered policy improvisation, and deviation, at the local level. Its suspension underscores the increasingly anti-Muslim, anti-religious tenor of PRC policy, as evidenced by the Sinicization campaign that was a proximate cause of WMC’s demise. Its demise also highlights ongoing efforts to reassert CCP control over government, business, and the Party’s own rank-and-file. The fate of WMC furthermore reveals the spatial dimensions of Sinicization, and of Chinese cultural governance past and present. To paraphrase theorist Henri Lefebvre, Sinicization entails “spatial practices” that impose Xi-ist “representations of space” on lived “representational spaces,” from mosques and businesses to theme parks and luxury resorts.
Zombie International Currency: The Pound Sterling 1945–1971
Authors: Avaro Maylis
Published: October 2024

This paper examines the international role of sterling during the Bretton Woods era and argues that it was not a competitor to the U.S. dollar. I construct a novel dataset to measure the reserve role of sterling in Europe and sterling area countries. The postwar reserve role of sterling was limited to the sterling area and was artificial as this area was built as a captive market. I document how British authorities imposed exchange controls, commercial threats, and economic sanctions on sterling area countries to compel them to keep their foreign exchange reserves in sterling.
The Belle-Epoque of Portfolios? How Returns, Risk, and Diversification Correlated with the Wealth Distribution in Paris in 1912
Authors: Pastore Thomas
Published: October 2024

I reconstruct the historical performance of individual portfolios owned by Parisian investors during the French Belle-Epoque, which was characterized by a massive concentration of wealth. Using the value of inherited bequests as a proxy for ex ante wealth, I show that wealthier investors not only exhibited greater betas and thus benefited from the bull market, but also captured positive alphas, which translated into greater Sharpe ratios. Their performance was enhanced by diversification tilted toward equity and foreign assets. I identify heterogeneity in returns as a significant driver of the rise of wealth inequalities during the Belle-Epoque.
Endogenous Political Legitimacy: The Tudor Roots of England’s Constitutional Governance
Authors: Greif Avner , Rubin Jared
Published: October 2024

This paper highlights the importance of endogenous changes in the foundations of legitimacy for political regimes. It focuses on the central role of legitimacy changes in the rise of constitutional monarchy in England. It first defines legitimacy and briefly elaborates a theoretical framework enabling a historical study of this unobservable variable. It proceeds to substantiate that the low-legitimacy, post-Reformation Tudor monarchs promoted Parliament to enhance their legitimacy, thereby changing the legislative process from the “crown and Parliament” to the “crown in Parliament” that still prevails in England. The break with Rome permanently altered England’s political development.
Fibre & fermented foods: differential effects on the microbiota-gut-brain axis
Authors: Schneider Elizabeth , Balasubramanian Ramya , Ferri Aimone , Cotter Paul D. , Clarke Gerard , Cryan John F.
Published: October 2024

The ability to manipulate brain function through the communication between the microorganisms in the gastrointestinal tract and the brain along the gut-brain axis has emerged as a potential option to improve cognitive and emotional health. Dietary composition and patterns have demonstrated a robust capacity to modulate the microbiota-gut-brain axis. With their potential to possess pre-, pro-, post-, and synbiotic properties, dietary fibre and fermented foods stand out as potent shapers of the gut microbiota and subsequent signalling to the brain. Despite this potential, few studies have directly examined the mechanisms that might explain the beneficial action of dietary fibre and fermented foods on the microbiota-gut-brain axis, thus limiting insight and treatments for brain dysfunction. Herein, we evaluate the differential effects of dietary fibre and fermented foods from whole food sources on cognitive and emotional functioning. Potential mediating effects of dietary fibre and fermented foods on brain health via the microbiota-gut-brain axis are described. Although more multimodal research that combines psychological assessments and biological sampling to compare each food type is needed, the evidence accumulated to date suggests that dietary fibre, fermented foods, and/or their combination within a psychobiotic diet can be a cost-effective and convenient approach to improve cognitive and emotional functioning across the lifespan.
Tragedy and ēthos in Andocides’ On His Return and at his later trial
Authors: Hill Theodore
Published: October 2024

This article argues that Andocides’ speech On His Return (Andocides 2) makes use of themes drawn from tragedy, including a near-quotation from Sophocles, in order to present the orator as deserving of pity and forgiveness. This neglected speech is therefore an ingenious work of rhetoric in its creation of ēthos and evocation of pathos. Moreover, it is a key document for the development of religious argumentation in the Athenian courts, and for the early reception of Sophocles. This also affects our interpretation of the two extant speeches from Andocides’ later trial in ca. 400, Against Andocides ([Lysias] 6) and On the Mysteries (Andocides 1), which both develop similar tragic themes in new directions.
The Value of the Creative Faculty in Man
Authors: Gill Eric
Published: October 2024

What is the nature of Man—“Quid est homo? … Constituisti eum super omnia opera manuum tuarum.” In what is this superiority? “I have said you are gods.” In what way are men as gods? What do we know of God? Credo in Deum … creatorem coeli et terrae. Creatorem—what does create mean? The Shorter Oxford Dictionary says: to bring into being; to cause to exist; to form out of nothing; to originate.

Now the existence of anything is dependent upon four causes. Take for example this table, (I) There is something that makes tables tables and not candlesticks; this kind of thing, not another kind. But, further, as an individual thing: this particular table and not that; a table like this one and not like that one—what makes tables tables, and this particular table this particular shape is the formal cause and without that cause this table would not exist.
Racial and ethnic disparities in social isolation and 11-year dementia risk among older adults in the United States
Authors: Grullon J. , Soong D. , Wong R.
Published: October 2024

Aims

Social isolation has been implicated in the development of cognitive impairment, but research on this association remains limited among racial-ethnic minoritized populations. Our study examined the interplay between social isolation, race–ethnicity and dementia.

Methods

We analyzed 11 years (2011–2021) of National Health and Aging Trends Study (NHATS) data, a prospective nationally representative cohort of U.S. Medicare beneficiaries aged 65 years and older. Dementia status was determined using a validated NHATS algorithm. We constructed a longitudinal score using a validated social isolation variable for our sample of 6,155 community-dwelling respondents. Cox regression determined how the interaction between social isolation and race–ethnicity was associated with incident dementia risk.

Results

Average longitudinal frequency of social isolation was higher among older Black (27.6%), Hispanic (26.6%) and Asian (21.0%) respondents than non-Hispanic White (19.1%) adults during the 11-year period (t = −7.35, p < .001). While a higher frequency of social isolation was significantly associated with an increased (approximately 47%) dementia risk after adjusting for sociodemographic covariates (adjusted hazard ratio [aHR] = 1.47, 95% CI [1.15, 1.88], p < .01), this association was not significant after adjusting for health covariates (aHR = 1.21, 95% CI [0.96, 1.54], p = .11). Race–ethnicity was not a significant moderator in the association between social isolation and dementia.

Conclusions

Older adults from racial-ethnic minoritized populations experienced a higher longitudinal frequency of social isolation. However, race–ethnicity did not moderate the positive association observed between social isolation and dementia. Future research is needed to investigate the underlying mechanisms contributing to racial-ethnic disparities in social isolation and to develop targeted interventions to mitigate the associated dementia risk.
Afterslip and Creep in the Rate‐Dependent Framework: Joint Inversion of Borehole Strain and GNSS Displacements for the Mw 7.1 Ridgecrest Earthquake
Authors: Hanagan C. , Bennett R. A. , Barbour A. , Hughes A. N.
Published: October 2024

The elusive transition toward afterslip following an earthquake is challenging to capture with typical data resolution limits. A dense geodetic network recorded the Mw 7.1 Ridgecrest earthquake, including 16 Global Navigation Satellite System (GNSS) stations and 3 borehole strainmeters (BSM). The sub‐nanostrain precision and sub‐second sampling rate of BSMs bridges a gap between conventional seismologic and geodetic methods, exemplified by atypical postseismic shear strain reversals observed at nearfield (<2 km) station B921 that remain unexplained. We jointly invert GNSS displacements and BSM strains for coseismic and postseismic slip spanning hours to months over 7 independent periods. Cosiesmically, our model resolves the largest slip magnitudes of up to 6.6 m on the mainshock rupture plane, with similar patterns to other inferred slip distributions. The foreshock fault appears to slip coincidently with mainshock, revealing potential asperities activated during the preceding Mw 6.4 event. Postseismically, the best‐fitting models adhere to mechanical rate‐and‐state expectations of logarithmically decaying slip adjacent to the coseismic rupture terminus, and where deep rheologic conditions favor creep. Most spatial variation occurs in the early postseismic timeframe (<1–2 weeks), with evidence for regional rheologic control and static stress dependence. Triggered creep on the neighboring Garlock Fault unexpectedly persists for >178 days—further highlighting the importance of fault networks in postseismic stress redistribution, critical to assessing future hazard.
Differential Phase Analysis for Volcanic Tremor Detection and Source Location
Authors: Barajas Andrés , Shapiro Nikolai M. , Prieto German
Published: October 2024

We present observations showing that during episodes of volcanic tremors, the phase of inter‐station cross‐correlations becomes stable. We propose a new quantity, the phase coherence, to identify the differential phase stability in recordings obtained from a single pair of stations, which is extrapolated to the seismic network. Then, we present a new approach based on the estimation of differential travel times through the differential phase measurements, to locate the sources of tremors occurring at the end of 2015 at the Klyuchevskoy Volcanic Group in Kamchatka, Russia. We present evidence supporting the existence of two types of activity happening simultaneously during the tremor episode: the main tremor source, originating from a region located between 7 and 9 km depth under the main volcanoes, and the widespread occurrence of weak low‐frequency earthquakes occurring at random locations. We show how the phase coherence and the differential phases can be used to provide information on the stability of the tremor source position and to estimate its location.
Pressure Monitoring of Disposal Reservoirs in North‐Central Oklahoma: Implications for Seismicity and Geostorage
Authors: Allen B. , Murray K. , Ogwari P. , Suriamin F. , Walter J. I. , Hayman N. W.
Published: October 2024

Disposal of industrial wastewater and activities such as underground sequestration depend upon pressure conditions within deep geologic reservoirs. Sometimes, injection and storage are associated with induced seismicity, suggested to result from reservoir compartmentalization, leakage into faults, or other mechanisms in the subsurface. To understand subsurface pressure conditions within a major regional disposal reservoir, the Arbuckle Group of Oklahoma, we monitored the water levels in 15 inactive injection wells. The wells were monitored at 30‐s intervals, with eight wells monitored since September 2016, and an additional seven from July 2017. All the wells were monitored until early March 2020. Since 2016, hydraulic head decreased in 13 of the 15 wells, proportional to near‐borehole fluid pressure even considering decreasing regional injection volumes during this period. The well pressures respond to three types of perturbations: (i) gravitational fluctuations (a.k.a. solid‐earth tides) (ii) distal and proximal earthquakes, and (iii) injections into nearby wells. Parameterization of tidal responses illustrates that the near wellbore environments have negative fluid flux (i.e., are leaking). Earthquakes cause differing pressure responses from well to well, with some highly sensitive to proximal events, some to distal events, and some apparently insensitive. Injections have variable impacts in some cases masking tidal and earthquake pressure signals. Collectively, there appears to be a threshold injection rate above which well pressure becomes less sensitive to the volume of injections within 15 km. Multi‐scale geological structure and temporal permeability changes are likely controlling the pressure field, indicating leakage of fluids across the system.
Living without pain: A 10-year study of congenital insensitivity to pain with anhidrosis
Authors: klaitman Shai Shlomi , ling Galina , Kristal Eyal , David Odeya , Elamour Siham , Hershkovitz Eli , Ling Eduard
Published: October 2024

Background

Congenital Insensitivity to Pain with Anhidrosis (CIPA) is a rare hereditary neuropathy caused by NTRK1 gene mutations, predisposing patients to recurrent infections and chronic wounds. Long-term studies on microbial and clinical outcomes in CIPA are limited. This study presents analysis of infection patterns, antibiotic resistance, and clinical outcomes in CIPA patients.

Methods

A comprehensive ten-year retrospective cohort study was conducted at Soroka University Medical Center, Beer Sheva, Israel, from January 2014 to January 2023. Electronic medical records were reviewed to identify 63 CIPA patients, all were of consanguineous Bedouin families. Data collection included demographic details, clinical presentations, genetic analysis, documentation of infections, wound sites, hospital duration, and surgical interventions.

Results

Staphylococcus aureus, notably methicillin-resistant, dominated, with Gram-negative bacteria common in lower limbs. The study noted reduced extended-spectrum beta-lactamase bacteria and linked demographic factors to infection traits, antibiotic resistance, and surgical needs.

Conclusion

This study provides valuable insights into the clinical and microbial patterns of CIPA, highlighting dynamic shifts in microbial compositions and antibiotic resistance profiles over time. Staphylococcus aureus, and Gram-negative bacteria particularly in lower limb infections, pose significant challenges in patient management. The findings underscore the importance of tailored approaches to address evolving microbial profiles and optimize patient care in CIPA.

Impact

Key Message: This is the largest cohort study on CIPA to date, highlighting the dominance of Staphylococcus aureus, including methicillin-resistant strains, and significant Gram-negative bacterial infections in lower limbs.

Contribution to Literature: It draws parallels between infection dynamics in CIPA and diabetic foot ulcers, emphasizing similar challenges due to neuropathy and ischemia, enhancing understanding of infection susceptibility and management in neuropathic conditions.

Impact: The findings inform clinical practices by detailing infection and resistance patterns, supporting the development of targeted treatment strategies to improve outcomes for CIPA and similar conditions.
Mechanism of curcumin in the prevention and treatment of oral submucosal fibrosis and progress in clinical application research
Authors: She Rong , Xu Pu
Published: October 2024

Introduction

Oral submucosal fibrosis is a potentially life-threatening oral disease that significantly impacts physiological functions such as speech and swallowing while also diminishing the quality of life for patients. Currently, the mainstream treatment for oral submucosal fibrosis in clinical practice involves invasive glucocorticoid drugs such as injection therapy. However, this method often leads to intraoperative pain, anxiety, fear, and poor medical experience due to associated side effects.

Methods

There is an urgent need to actively explore new drugs and relatively noninvasive approaches for the treatment of oral submucosal fibrosis in order to enhance patients’ medical experience and compliance. This has become a focal point of attention in clinical research. After conducting an extensive literature search, it was discovered that curcumin, a natural polyphenolic compound, exhibits potent anti-tumor, anti-inflammatory, antioxidant, anti-metastatic and anti-angiogenic properties. Moreover, curcumin holds significant clinical potential in the prevention and treatment of various diseases such as oral submucosal fibrosis.

Conclusion

This review presents a comprehensive elaboration encompassing the action mechanisms, biological activity, potential applications, and clinical characteristics of curcumin in the management of oral submucosal fibrosis, aiming to provide diagnostic insights and novel therapeutic perspectives for its prevention and treatment.
One-carbon-mediated purine synthesis underlies temozolomide resistance in glioblastoma
Authors: Ghannad-Zadeh Kimia , Ivanova Alyona , Wu Megan , Wilson Taylor M. , Lau Alyssa , Flick Robert , Munoz David G. , Das Sunit
Published: October 2024

Glioblastoma accounts for nearly half of all primary malignant brain tumors in adults, and despite an aggressive standard of care, including excisional surgery and adjuvant chemoradiation, recurrence remains universal, with an overall median survival of 14.6 months. Recent work has revealed the importance of passenger mutations as critical mediators of metabolic adaptation in cancer progression. In our previous work, we identified a role for the epigenetic modifier ID-1 in temozolomide resistance in glioblastoma. Here, we show that ID-1-mediated glioblastoma tumourigenesis is accompanied by upregulation of one-carbon (1-C) mediated de novo purine synthesis. ID-1 knockout results in a significant reduction in the expression of 1-C metabolism and purine synthesis enzymes. Analysis of glioblastoma surgical specimens at initial presentation and recurrence reveals that 1-C purine synthesis metabolic enzymes are enriched in recurrent glioblastoma and that their expression correlates with a shorter time to tumor recurrence. Further, we show that the 1-C metabolic phenotype underlies proliferative capacity and temozolomide resistance in glioblastoma cells. Supplementation with exogenous purines restores proliferation in ID-1-deficient cells, while inhibition of purine synthesis with AICAR sensitizes temozolomide-resistant glioblastoma cells to temozolomide chemotherapy. Our data suggest that the metabolic phenotype observed in treatment-resistant glioma cells is a potential therapeutic target in glioblastoma.
Lyophilised amniotic membrane patches are a safe and effective treatment for rhegmatogenous lesions in combined tractional and rhegmatogenous retinal detachment: a prospective interventional study
Authors: García-Vásquez Ángel , Rojas-Juárez Sergio , Rios-Nequis Geovanni , Ramirez-Estudillo Abel
Published: October 2024

Objectives

This study was performed to evaluate the safety and effectiveness of a lyophilised amniotic membrane (LAM) as a patch for the treatment of retinal breaks and to describe the structural changes at the implantation site.

Design

Prospective, interventional case series study. Patients with diabetic retinopathy and combined tractional and rhegmatogenous retinal detachment.

Methods

Patients were organised into 3 groups according to the number of rhegmatogenous lesions: those in group A had a single break, those in group B had two breaks, and those in group C had three or more breaks. The location of the break was also evaluated as either superior or inferior. Structural outcomes were assessed using SD-OCT during a 3-month follow-up period.

Results

Of a total of 23 eyes of 23 patients, 22 (95.6%) achieved retinal repair without associated complications. Patients with 2 or fewer rhegmatogenous lesions located in the superior sector had a better anatomical result as they achieved 100% surgical success. The structural changes observed by SD-OCT over the follow-up period showed adequate adaptation of the lyophilised patch and complete closure of the rhegmatogenous lesion with no alterations in the adjacent tissue.

Conclusions

The LAM patch seems to be safe and effective, as it promotes therapeutic closure of rhegmatogenous lesions without damaging the retinal architecture adjacent to the implantation site.
Persistence and recurrence after removal of idiopathic epiretinal membrane
Authors: Reichel Felix F. , Labbe Eduardo , Gelisken Faik , Seitz Immanuel P. , Hagazy Sherif , Dimopoulos Spyridon
Published: October 2024

Objectives

To analyse the incidence of persistence and recurrence after the peeling of idiopathic epiretinal membrane (ERM) and to describe its clinical features.

Methods

This retrospective study included 666 eyes (645 patients) that underwent macular surgery for ERM removal. Optical coherence tomographic (OCT) images taken within three months after surgery and at the following visits, clinical parameters and surgery related factors were analysed to investigate the incidence and associated factors of ERM persistence and recurrence. Postoperative ERM types were categorised depending on the size ( < 100 µm, ≥100 µm) and the location (foveal, parafoveal, outside the parafovea)

Results

The mean follow-up time was 29.4 months. ERM persistence (examination within 3 months) was found in 29.6% of all eyes. Only 1.9% of the eyes presented foveal ERM persistence. Foveal recurrence, defined as reappearance or growth of persistent ERM covering the fovea, was found in 8.2%. In 84.4% of eyes with foveal ERM recurrence, postoperative persistence of ERM of varying severity were identified. None of the pre-operative or surgery related factors were found significantly associated with ERM recurrence. Persistent ERM within the parafovea was the most significant risk factor for foveal ERM recurrence.

Conclusion

Recurrence of ERM is generally preceded by the persistence of ERM fragments found in the early postoperative period. Growth of ERM persistence from the parafoveal region was often the origin of foveal ERM recurrence. Insufficient peeling seems to be the most significant predisposing factor for foveal ERM recurrence.
Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling
Authors: Zhang Hailong , Hasegawa Yuko , Suzuki Masataka , Zhang Ting , Leitner Deborah R. , Jackson Ruaidhrí P. , Waldor Matthew K.
Published: October 2024

Serotonergic neurons in the central nervous system control behavior and mood, but knowledge of the roles of serotonergic circuits in the regulation of immune homeostasis is limited. Here, we employ mouse genetics to investigate the functions of enteric serotonergic neurons in the control of immune responses and find that these circuits regulate IgA induction and boost host defense against oral, but not systemic Salmonella Typhimurium infection. Enteric serotonergic neurons promote gut-homing, retention and activation of intestinal plasmacytoid dendritic cells (pDC). Mechanistically, this neuro-immune crosstalk is achieved through a serotonin-5-HT receptor 7 (HTR7) signaling axis that ultimately facilitates the pDC-mediated differentiation of IgA+ B cells from IgD+ precursors in the gut. Single-cell RNA-seq data further reveal novel patterns of bidirectional communication between specific subsets of enteric neurons and lamina propria DC. Our findings thus reveal a close interplay between enteric serotonergic neurons and gut immune homeostasis that enhances mucosal defense.
Enhanced ocean CO2 uptake due to near-surface temperature gradients
Authors: Ford Daniel J. , Shutler Jamie D. , Blanco-Sacristán Javier , Corrigan Sophie , Bell Thomas G. , Yang Mingxi , Kitidis Vassilis , Nightingale Philip D. , Brown Ian , Wimmer Werenfrid , Woolf David K. , Casal Tânia , Donlon Craig , Tilstone Gavin H. , Ashton Ian
Published: October 2024

The ocean annually absorbs about a quarter of all anthropogenic carbon dioxide (CO2) emissions. Global estimates of air–sea CO2 fluxes are typically based on bulk measurements of CO2 in air and seawater and neglect the effects of vertical temperature gradients near the ocean surface. Theoretical and laboratory observations indicate that these gradients alter air–sea CO2 fluxes, because the air–sea CO2 concentration difference is highly temperature sensitive. However, in situ field evidence supporting their effect is so far lacking. Here we present independent direct air–sea CO2 fluxes alongside indirect bulk fluxes collected along repeat transects in the Atlantic Ocean (50° N to 50° S) in 2018 and 2019. We find that accounting for vertical temperature gradients reduces the difference between direct and indirect fluxes from 0.19 mmol m−2 d−1 to 0.08 mmol m−2 d−1 (N = 148). This implies an increase in the Atlantic CO2 sink of ~0.03 PgC yr−1 (~7% of the Atlantic Ocean sink). These field results validate theoretical, modelling and observational-based efforts, all of which predicted that accounting for near-surface temperature gradients would increase estimates of global ocean CO2 uptake. Accounting for this increased ocean uptake will probably require some revision to how global carbon budgets are quantified.
A multiple session dataset of NIRS recordings from stroke patients controlling brain–computer interface
Authors: Isaev Mikhail R. , Mokienko Olesya A. , Lyukmanov Roman Kh. , Ikonnikova Ekaterina S. , Cherkasova Anastasiia N. , Suponeva Natalia A. , Piradov Michael A. , Bobrov Pavel D.
Published: October 2024

This paper presents an open dataset of over 50 hours of near infrared spectroscopy (NIRS) recordings. Fifteen stroke patients completed a total of 237 motor imagery brain–computer interface (BCI) sessions. The BCI was controlled by imagined hand movements; visual feedback was presented based on the real–time data classification results. We provide the experimental records, patient demographic profiles, clinical scores (including ARAT and Fugl–Meyer), online BCI performance, and a simple analysis of hemodynamic response. We assume that this dataset can be useful for evaluating the effectiveness of various near–infrared spectroscopy signal processing and analysis techniques in patients with cerebrovascular accidents.
The impact of education level on all-cause mortality in patients with atrial fibrillation
Authors: Sztaniszláv Áron , Björkenheim Anna , Magnuson Anders , Bryngelsson Ing-Liss , Edvardsson Nils , Poci Dritan
Published: October 2024

The association of socioeconomic status with cardiovascular morbidity and mortality is well known, but data on the influence of education level on mortality in individuals with atrial fibrillation (AF) are scarce. We investigated education level as a predictor of all-cause mortality in patients diagnosed with AF. This retrospective cohort study used a database created from several Swedish nationwide registries to identify all patients hospitalized with a diagnosis of AF hospitalized from 1995 to 2008. Education level was categorized as primary, secondary, and academic. All-cause mortality risk was estimated in subpopulations defined by the Charlson Comorbidity Index and several comorbidities. A total of 272,182 patients (56% male; mean age 72 ± 10 years) were followed for five years. Cox regression models showed a reduction in all-cause mortality risk with increased education level. Hazard ratios (HR) relative to primary education remained significant after stratification and adjustment for several confounders: secondary education HR = 0.88; 95% CI: 0.86–0.89; P < 0.001; academic education HR = 0.70; 95% CI: 0.67–0.72; P < 0.001. Subpopulation analyses confirmed a significant reduction in relative risk with higher education level. Targeted screening and education programs could be effective in reducing mortality in AF patients with fewer years of formal education.
Eyestrains among smartphone users while watching videos in Taipei MRT carriages: a comparison between sitting and standing postures
Authors: Chen Yi-Lang , Chu Kuo-Hao , Huang Po-Chun , Ho Chieh-Ting , Nguyen Hong-Tam
Published: October 2024

In MRT carriages, more passengers are watching videos on their smartphones during daily commutes, yet the impact of these viewing conditions on visual strain remains unexplored. This study examined eyestrain in 24 male and 24 female participants while watching videos on smartphones in two postures (sitting and standing) and over two durations (15 min and 30 min) in Taipei MRT carriages. We measured critical flicker fusion frequency (CFF) reduction, visual fatigue scale (VFS) scores, and viewing distance (VD) for each trial. Results revealed significant effects of sex, posture, and viewing duration on visual strain, with notable two-way interactions (sex × posture and posture × time) influencing most outcomes. Women showed greater CFF reduction while sitting compared to standing (3.47 Hz vs. 1.90 Hz, p < 0.001) and maintained shorter VDs while seated (25.5 cm vs. 34.3 cm, p < 0.001). However, they reported higher VFS scores when standing (8.94 vs. 4.60, p < 0.001), indicating increased discomfort while standing in the moving MRT carriage. Men exhibited higher CFF reduction (2.81 Hz) than women while standing (1.90 Hz) (p < 0.01), but this difference was not observed while sitting. Eyestrain indicators significantly worsened after 30 min of viewing compared to 15 min, with stronger effects on VFS scores and VDs. This finding supports the recommendation to take breaks after 20 min of smartphone use, even in MRT carriages. Although subjective eyestrain is not always recognized, watching videos on smartphones while seated can result in unexpectedly high levels of objective visual fatigue, indicated by CFF reduction. Our findings suggest that eyestrain patterns in MRT carriages differ from those reported in previous studies. Seated passengers, particularly females with shorter VD, may experience unrecognized eyestrain that could impact eye health, while standing passengers may face greater discomfort. These results highlight the need for increased awareness and preventive measures to mitigate eyestrain in digital public transportation environments.