bluuebunny/crossref_metadata_2025 huggingface dataset:
Overview of the future perspective of Aerofoil-Based Passive Heat Transfer Enhancement
Authors: Jadhao Rohit Rajendra , Chitragar Parashuram Ramana , Kamble Dattatray
Published: February 2025

With increasing demands for sustainability and energy efficiency in various industrial applications, inefficient heat transfer systems have received much attention. This abstract provides an ability that involves aerofoil-based passive heat transfer enhancement. Aerofoil-shaped structures inspired by aerodynamic principles have shown promise to enhance heat transfer without the need for external power sources. Understanding the capabilities and challenges of aerofoil-based passive approaches is important for the advancement of thermal management in a variety of applications including aerospace, industrial applications, renewable energy systems, electronics cooling and automotive systems. The study also considers various geometries, materials, and configurations to evaluate the impact on heat transfer performance. Furthermore, the underlying mechanisms governing the enhanced heat transfer in aerofoil-like structures are explored.The summary of the results includes key findings from studies investigating the use of aerofoil systems to enhance passive heat augmentation. It evaluates the effectiveness of different aerofoil geometries for heat enhancement performance by providing a comparative review analysis of parameters such as heat transfer coefficient, Nusselt number and thermal resistance in different passive enhancement techniques. The result also highlights the advantage of aerofoil-based passive techniques which demonstrate adaptability and versatility. This review concludes by providing a future perspective on the potential of aerofoil-based passive heat transfer enhancement.Knowledge gathered from recent studies shows a promising approach for aerofoil-like structures to significantly improve thermal performance in various industries. The findings highlight the need for continued research and innovations to overcome existing challenges and to fully exploit the potential of passive aerofoil-based techniques. The insights presented in this overview are intended to guide researchers, engineers, and policymakers in applying aerofoil-based methods for large-scale thermal systems in the upcoming years.
Potential use of bio- ethanol performance on variable compression ratio petrol engine
Authors: Kulkarni Srikar G , Navindgi M C
Published: February 2025

India is among the world’s fastest growing economies. The demand for crude oil and petroleum products is high and increasing. Fossil fuels have traditionally served as the primary energy source for the transportation industry. Biofuels, on the other hand, have recently acquired popularity as realistic replacements with significant economic and environmental benefits. In terms of energy usage, India comes in third place worldwide. India’s fuel ethanol initiative is largely motivated by two objectives: lowering emissions and reducing dependency on fossil fuels. Petroleum provides the vast majority of the world’s energy. Growing energy use and overreliance on imports raise serious worries about energy security. Its Energy demands are mostly satisfied by oil, which it continues to buy in large amounts from other nations. India will have doubled its energy consumption by 2050. Increased energy use and reliance on imports pose a severe threat to energy security. Furthermore, it results in a massive outflow of foreign exchange. A 4.75 kW gasoline engine with a variable compression ratio that was in sync with IC Engine software 9.0 was used for the testing in order to assess the feasibility of employing bioethanol blends. The blends were created on a volume basis in the following proportions: 05:95, 10:90, 15:85, 20:80, 25:75, and 30:70. They were referred to as E5, E10, E15, E20, E25, and E30 in comparison to gasoline E0. The findings indicate that bioethanol may be mixed with petrol up to E20 without requiring engine modifications, However, large percentage of biethanol combinations will not perform properly. . The emission parameters of the E20 bioethanol mix have produced good results and met emission standards out of all the blends studied. Developing nations like India may have the raw materials required to enhance bioethanol production. A higher minimum support price for sugarcane harvest benefits farmers economically.
Devoted to Death
Authors: Chesnut R Andrew
Published: February 2025

R. Andrew Chesnut offers a fascinating portrayal of Santa Muerte, a skeleton saint whose cult has become the fastest growing new religious movement on the planet over the past two decades. Although condemned by mainstream churches, this folk saint’s supernatural powers appeal to millions in Latin America, the U.S., and beyond. Devotees believe the Bony Lady (as she is affectionately called) to be the fastest and most effective miracle worker, and as such, her statuettes and paraphernalia now outsell those of the Virgin of Guadalupe and Saint Jude, two other giants of Mexican religiosity. In particular, Chesnut shows Santa Muerte has become the patron saint of drug traffickers, playing an important role as protector of peddlers of fentanyl and marijuana; DEA agents and Mexican police often find her altars in the safe houses of drug smugglers. Yet Saint Death plays other important roles: she is a supernatural healer, love doctor, moneymaker, lawyer, and angel of death. She has become without doubt one of the most popular and powerful saints on both the Latin American and American religious landscapes.
Brown Candle
Authors: Chesnut R Andrew
Published: February 2025

Chapter 1 delves into the multifaceted origins and development of the devotion to Santa Muerte, a figure entwined with both ancient Indigenous beliefs and European influences. It highlights the contrast between devotees’ focus on the saint’s miraculous powers and the academic interest in her historical and cultural roots. The narrative explores Santa Muerte’s identity, tracing her evolution from the Aztec goddess Mictecacihuatl to a symbol of Mexicanness and a folk saint blending Catholic and Indigenous traditions. The chapter weaves together myths, reality, and scholarly analysis to offer insights into the complexities of this New Religious Movement (NRM), showcasing Santa Muerte’s significance beyond her role as a mere deity of death, embodying a deeper connection to Mexican identity and spirituality.
White Candle
Authors: Chesnut R Andrew
Published: February 2025

This chapter encapsulates the essence and diversity of practices and beliefs surrounding Santa Muerte, a figure deeply rooted in Mexican spirituality and folk religion. This narrative delves into the personal journey of an academic, initially seeking a Virgin of Guadalupe candle, whose curiosity leads to the discovery of Santa Muerte paraphernalia in a local supermarket. This encounter marks the beginning of a profound exploration into the beliefs and practices associated with Santa Muerte, highlighting the figure’s multifaceted role in the lives of her devotees. The narrative reveals Santa Muerte’s transformation from a secretive figure of devotion into a prominent folk saint, reflecting the complex interplay among religion, culture, and identity. Through personal anecdotes, scholarly insights, and vivid descriptions of rituals and offerings, the text provides a comprehensive overview of the Santa Muerte cult, illustrating its significance in contemporary society and its deep connections to themes of protection, healing, and justice. Santa Muerte’s portrayal as a powerful and compassionate figure resonates with a wide array of followers, from those seeking divine intervention in daily struggles to individuals navigating the challenges of love, health, and justice. This chapter highlights the depth and diversity of Santa Muerte’s worship, emphasizing her role as a symbol of resilience, empowerment, and spiritual solace for many.
The Courtiers and the Court of Louis XIII, 1610–1643
Authors: Jaffré Marc W S
Published: February 2025

This book presents the first comprehensive study of Louis XIII’s court. The book charts the evolutions of the French court at a key-stage in its development, before the elaboration of Louis XIV’s Versailles model. Its chapters cover the court’s institutional development, politics at the court, ceremonial, entertainment, and the court’s itinerancy, but also topics less usually associated with the court, such as court finance, the merchants and artisans of the court, and how the court functioned when the king went to war. Throughout the book, the political, cultural, and material investment of courtiers (ranging from lowly coat-bearers to the most powerful princes) in the court as an institution is brought to the fore, proving just how central the court was to Louis XIII’s France. The delegitimizing and destabilizing role played by Cardinal Richelieu as minister-favourite is an important theme running through the book, providing new perspectives on the function of royal favourites within the early modern state. Through its study of Louis XIII’s court, this monograph demonstrates the agency people have in shaping the institutions in which they act and that are important to them. The monograph does this by emphasizing the role that courtiers, artisans, merchants, and financiers played in shaping the institutional, political, cultural, economic, and military framework of Louis’s court. In challenging the top-down paradigm prevalent in court studies, this monograph provides crucial correctives to the existing narrative that Louis XIII’s court was weak or unimportant and simultaneously revises how early modern courts and their development have been understood historiographically.
‘Confusion from the Kitchens to the Cabinet’: The Royal Household Indoors
Authors: Jaffré Marc W S
Published: February 2025

Chapter 1 provides an overview of the institutional development of the household departments of the Chamber, the Kitchens, and the Royal Chapel during the reign of Louis XIII. It complicates narratives that associate political instability with a growth in household size and emphasizes the ways in which department heads, like the grand master of France, and lower ranking household officers sought to alter the scope of their offices in order to safeguard or increase their access to the monarch, the financial benefits that could be gained from their offices, and the prestige tied to their offices. The chapter shows that household officers did not view their functions, privileges, or authority as fixed, and that it was their attempts to alter the terms of their service to their advantage that fuelled the fluctuations in the numbers of household officers within a department, the creation of new offices, and other institutional modifications. This activity, perceived by Cardinal Richelieu as disorder, was a sign of courtiers’ investment in household institutions and the court’s vitality as a whole.
‘This Crown is like a Vacant Abbey’: Favour, Faction, and Politics
Authors: Jaffré Marc W S
Published: February 2025

Chapter 3 examines how politics functioned at the court of Louis XIII, emphasizing Cardinal Richelieu’s complex relationship with the royal household, how Louis’s reliance on favourites affected factional politics and created problems of legitimacy, and the political importance of the satellite courts and households of Louis’s family members. It emphasizes the difficulties Richelieu had in managing the royal household due to the lack of household offices that were appropriate to both his status and political aims. This forced him to rely on proxies and a network of spies in order to manage the household. But it was an unreliable method of control, and he was forced at regular intervals to purge erstwhile allies, fuelling political instability at court. The energy Richelieu spent in managing the king’s household shows that he understood very well the continuing importance of court politics and that in practice power remained firmly rooted in the king’s person. At the same time, the chapter demonstrates how Richelieu’s discourse of reason of state forced those who did not agree with his policies into either armed rebellion or court conspiracy as dissenters were left without avenues for reconciliation. Far from shielding Louis XIII from unpopular political decisions, Louis’s reliance on Cardinal Richelieu as a minister-favourite was a destabilizing force because Richelieu and other favourites lacked the ability to confer legitimacy on their actions and the factions they belonged to. This left them particularly vulnerable to the political opposition of royal family members and their satellite courts.
‘Maintained in the Rank in Which he Belongs’: The Court, Courtiers, and the Development of Royal Ceremonial
Authors: Jaffré Marc W S
Published: February 2025

Chapter 4 analyses royal ceremonial during Louis XIII’s reign and emphasizes the role of courtiers both in ceremonial’s development and in shaping its meanings. The chapter begins with an overview of the officers involved in the ordering of royal ceremonies and reveals that the period was characterized not just by a growth in the number of ceremonial officers but also by an increasing interest in researching records and building archives of information relating to ceremonies. The chapter then proceeds to examine sacral kingship through an analysis of Louis’s coronation, funerary practices, the ceremony of the king’s touch, and ceremonies relating to foot washing (pedilavium). This examination highlights the multiple, confused meaning of ceremonies, and challenges ideas that kingship was programmatic or clearly thought out. It additionally demonstrates how wider noble trends and fashions could impact royal ceremonial practice. This chapter also finds that everyday ceremonial—such as the king’s lever, his coucher, and royal dining rituals—did not generate as many disputes as larger scale ceremonies, but that this was because these rituals were less visible rather than because the nobility was not invested in court ceremonial. On the contrary, shifting focus onto the nobility reveals the extent to which they tried to stamp their own meanings onto the ceremonies they participated in and simultaneously shines a light on a variety of daily court ceremonies, such as the swearing of oaths, courtiers’ baptism ceremonies, and conversion ceremonies, that were of pivotal importance for all the courtiers involved.
‘From Shoemaker I Could Become Councillor’: Merchant Courtiers’ Strategies and Ambitions
Authors: Jaffré Marc W S
Published: February 2025

Chapter 7 examines the merchants and artisans employed by Louis XIII’s court and their role within court society. The chapter emphasizes how large and varied the groups of merchants working for the court were as well as the different methods of remuneration employed by the court. Merchants mitigated risks involved with contracting with the court and maximized profits by forming associations with each other and by subcontracting part of their work to Parisian merchants. Court merchants benefited tremendously from exemptions from tax and custom duties, exemptions from guild structures, and the right to have their cases tried by the Provostship of the Household. Their exemptions led them to clash frequently with tax farmers and urban guilds, and it was a considerable advantage to be able to turn to the Provostship for support as it also relied on court merchants to help reinforce its own contested jurisdictional claims. Court merchants and artisans additionally exploited their court connections to participate in court society, pursue noble marriages for their daughters, acquire household offices, and elevate themselves into the nobility. The chapter reveals that court merchants were fully fledged courtiers, for whom the opportunity to participate in court society was one of the primary motivations for contracting with the court.
Melatonin modulated GPX5 and PTGDS expression in Bactrian camel epididymis mainly via receptor MT1
Authors: Zhao Shuqin , Wu Shipeng , Ji Shuai , Han Yaxuan , Yang Zhen , Gao Yuan
Published: February 2025

Melatonin (Mel), an important mediator of photoperiodic annual rhythm regulation and seasonal reproduction in animals, directly modulates the expression of specific genes in the epididymis and protects sperm from oxidative damage. Bactrian camel is a dominant species in desert and semi-desert areas, exhibiting the unique reproductive regulation patterns. However, the underlying regulation mechanism of Mel on Bactrian camel is still unclear. This study isolated the epididymal caput epithelial cells of Bactrian camels and investigated the expression of specific genes involving sperm protection after Mel treatment and overexpression/knockdown of Mel receptor MT1/MT2 using real-time quantitative PCR assay (qPCR), ELISA, and western blotting assay. The results showed that MT1, MT2, clock genes cryptochrome 1/2 (Cry1/Cry2) were all positively expressed in the epididymal lumen epithelial cells, peritubular myoid cells, and luminal spermatozoa. Intriguingly, Mel treatment activated receptor MT1 in epididymal caput epithelial cells, indicating that Mel treatment regulated genes expression mainly via MT1-dependent manner. Mel treatment or overexpression of MT1 both increased secretion of glutathione peroxidase 5 (GPX5) and prostaglandin D2 synthase (PTGDS), and MT1 silencing induced downregulation of GPX5 and PTGDS expression, indicating that the expression of GPX5 and PTGDS were regulated by Mel-MT1. Overexpression of MT1 or MT2 promoted Cry2 expression, and overexpression of Cry2 also activated the MT1/MT2 expression by feedback regulation. Finally, the double luciferase reports assay showed that the activation of MT1 by Cry2 occurred during transcription. These results help to understand the regulatory effect of Mel on the epididymis in Bactrian camels.
Papillon-Lefèvre syndrome: palmoplantar keratoderma with teeth abnormalities
Authors: Gupta Priyansh , Sangwan Priyanka , Thakur Vishal , Behera Biswanath
Published: February 2025

In this manuscript we have shown the clincal images of a patient with papillon lefevre syndrome confirmed with genetic analysis. Knowledge of such syndromes is important as they can be clinically suspected in backgrund of other findings like periodontitis.
Surgical tricuspid edge-to-edge repair: double-orifice repair versus clover repair
Authors: Lee Heemoon , Kim Jihoon , Jung Ji-Hyun , Yoo Jae Suk
Published: February 2025

OBJECTIVES

Surgical edge-to-edge repair has been proposed to treat tricuspid regurgitation with various etiologies. Two techniques can be used for this repair: the “double-orifice” and the “clover” repairs. This study compares the clinical outcomes of these two techniques.

METHODS

The study enrolled 258 patients who underwent tricuspid edge-to-edge repair out of 2,257 tricuspid valve repairs between January 2001 and December 2021. Patients were categorised into two groups (double-orifice and clover repairs) and analysed using propensity score matching.

RESULTS

The mean age of the 258 patients was 60.8 ± 12.4 years, with 190 females (73.6%) and a mean EuroScore II of 4.6 ± 5.5. Of these, 169 underwent double-orifice repair and 89 clover repair, adjusted to 118 and 66 after matching, respectively. Using the reverse Kaplan–Meier method to account for censored data, the median follow-up duration[Q1–Q3] was 169[76–229] months. Early mortality and morbidity did not differ significantly between the groups. Survival analysis did not show statistical differences in overall mortality and late severe tricuspid regurgitation recurrence between the groups. Similarly, freedoms from late significant tricuspid stenosis (trans-tricuspid pressure gradient ≥5 mmHg) and tricuspid reoperations (8[4.7%] in the double-orifice repair group and 2[2.2%] in the clover repair group) were not significantly different between the groups. The sensitivity analysis, which included the inverse probability of treatment weighting analysis, produced consistent results.

CONCLUSIONS

The surgical outcomes of tricuspid edge-to-edge repair were not statistically significantly different, regardless of the repair techniques. Both methods can be valuable options for tricuspid regurgitation repair.
Current status of aortic valve repair surgery
Authors: De Paulis Ruggero , Chirichilli Ilaria , de Kerchove Laurent , Della Corte Alessandro , El Khoury Gebrine , Michelena Hector I , Salica Andrea , Schäfers Hans-Joachim
Published: February 2025

Severe aortic valve regurgitation, if not timely treated, can significantly impact patients’ survival both for tricuspid aortic valve and bicuspid aortic valve patients, with the latter being significantly younger. Increased understanding of the root anatomy and its physiology has opened the way to techniques of aortic valve repair surgery. The techniques mainly relate to re-establishing a correct root and annular geometry and eliminating leaflet prolapse. These techniques are applied both in the presence of a dilated and normal root and are equally valid for tricuspid or bicuspid valve. Techniques for repairing a bicuspid valve might vary depending on the different valve phenotypes. Medium and long-term results appear favourable and potentially superior to those of prosthetic replacement in terms of valve-related complications and quality of life. Optimal surgical treatment, especially in younger and selected patients, should aim to avoid aortic valve replacement and its related complications.
Case analysis and finite element analysis of adult head skull fractures in people run over by motor vehicles
Authors: Yang Xingan , Chen Xinzhe , Zhang Fu , Yang Tengfei , Kong Jiangwei , Liao Xinbiao , Li Dongri
Published: February 2025

The cranial stress distribution and morphological characteristics of cranial fractures in adult heads run over by motor vehicle were investigated. Cases of adults’ heads being run over by motor vehicles were collected. The skull fracture degrees are categorized by no skull fracture, multiple skull fractures and skull fractures with brain tissue overflow. According to China’s road traffic management system, vehicles in traffic accidents are categorized heavy vehicles (weight ≥ 12 tons), medium vehicles (4.5 tons≤weight < 12 tons), light vehicles (1.8 tons<weight < 4.5 tons), and light minicars (weight ≤ 1.8 tons). Finite element simulations were used to analyze the relationship between cranial fracture morphology and vehicle weight as well as cranial stress response. A total of 41 cases of heads run over by motor vehicle were collected. In seven cases of multiple skull fractures caused by medium vehicle running over, there were head skull fractures on both the ground side and the tire side, and the degree of head skull fracture was more serious on the ground side than on the tire side. Finite element simulations showed that the cranial stress in the head was more concentratedly distributed on the ground side than on the tire side. Light vehicles and light minicars run over a head usually do not fracture the skull. Head injuries caused by medium vehicle running over are mainly characterized by multiple skull fractures, and the degree of skull fracture is more serious on the ground side than on the tire side.
The role and reach of alcohol reduction apps
Authors: Uscher-Pines Lori , Sousa Jessica L , Mehrotra Ateev , Busch Alisa B , Horgan Constance M , Huskamp Haiden A
Published: February 2025

Although apps are widely available and have several advantages as a tool to support alcohol reduction and recovery, little is known about how individuals are using them. In 2024, we conducted an exploratory sequential mixed-methods study that coupled in-depth interviews with 22 app users and a nationally representative survey of 2002 adults. We explored experiences with and perceptions of alcohol reduction apps. Approximately 6% of US adults in the sample reported using alcohol reduction apps, and for most, it was the only support to address problematic drinking. In interviews, some users viewed apps as an alternative to traditional services and a way to independently address alcohol use; however, apps were seen as disconnected from care even by those who also used other supports. App users accessed a variety of features, with the most common being motivational content, tracking alcohol consumption, and educational content. Findings suggest that there are opportunities to not only introduce apps to individuals receiving healthcare services or participating in mutual support groups, but to reference and embed them in those settings. New approaches to regulation and reimbursement may support adoption as well as integration into healthcare services.
Switching between medicare advantage and traditional medicare for individuals newly diagnosed with cancer 2015-2019
Authors: Parsons Helen M , Greenwald Samuel J , Jarosek Stephanie , Nikpay Sayeh , Clark Roxanne M , Shippee Nathan , Henning-Smith Carrie , Enewold Lindsey
Published: February 2025

Background

Medicare Advantage (MA) plans may offer more benefits and lower costs relative to Traditional Medicare (TM), but may also provide narrower provider networks and pre-authorization requirements. We explore the impact of a cancer diagnosis on switching between MA and TM after diagnosis.

Methods

We used the 2015-2019 Surveillance, Epidemiology and End Results-Medicare data to examine patterns of switching between MA and TM after cancer relative to those without cancer. We used binomial generalized estimating equations to evaluate the cancer and sociodemographic characteristics of those with higher probabilities of switching.

Results

Among those initially enrolled in MA plans (39.27% of those with vs 40.79% without cancer), 3.76% of individuals with cancer switched to TM compared to 2.23% without cancer. For those initially enrolled in TM, 2.96% of individuals with cancer switched to MA vs 4.35% without cancer. Multivariable analyses demonstrated that, among individuals starting in MA, a cancer diagnosis was associated with a 52.02% increase in switching relative to those without cancer, whereas among those starting in TM, a cancer diagnosis was associated with a 26.90% reduction in switching. Younger individuals, males, dual-eligible, those with more comorbidities, rural-dwellers, and those living in zip codes with higher education and income levels also had higher probabilities of switching from MA to TM.

Conclusions

Prior to diagnosis, MA enrollment is comparable between individuals with and without cancer. However, after diagnosis, individuals with cancer have higher probability of switching from MA to TM and lower probability of switching from TM to MA.
Drivers of root-associated fungal community structure in a common drought tolerant shrub at a regional scale
Authors: Chen Deqiang , Yang Juanjuan , Wu Chunping , Li Linyi , Lan Siren , Zhang Dianxiang , Liu Zhong-Jian , Qian Xin
Published: February 2025

Plant root-associated fungal communities are pivotal for enhancing plant growth, nutrient absorption, disease resistance, and environmental stress adaptation. Despite their importance, the assembly processes of these communities remain inadequately explored. In this study, we utilized high-throughput sequencing, co-occurrence network analysis, and null models to perform an extensive examination of the diversity, composition, interaction patterns, and assembly mechanisms of the root-associated fungal communities of Mussaenda pubescens, a drought tolerant shrub that can thrive in stressful environments and which is widely used for Chinese medicine. Our findings revealed pronounced regional and ecological niche-based variations in the diversity and assembly of total fungi and essential functional guilds, including saprotrophs, symbiotrophs, and plant pathogens. Significantly, the fungal diversity of plant pathogens decreased with elevation, whereas total fungi, saprotrophs, and symbiotrophs were minimally affected. Stochastic processes, such as dispersal limitation, play a significant role in fungal assembly. Furthermore, soil physicochemical properties, climatic conditions, and spatial variables also emerged as critical determinants of fungal community structure. This study enriches our understanding of the dynamics governing root-associated fungal community assemblies and underscores the factors essential for sustaining fungal diversity.
Unveiling spatial heterogeneity in medulloblastoma: a multi-omics analysis of cellular state and geographical organization
Authors: Li Jiankang , Liu Hailong , Wang Ziwei , Zhang Jiao , Chen Xuan , Daniels Craig , Wu Xiaochong , Saulnier Olivier , Suzuki Hiromichi , De Antonellis Pasqualino , Rasnitsyn Alexandra , Ong Winnie , Wang Evan Y , Hendrikse Liam D , Su Yu , Tian Yu , Han Dongming , Wang Ruohan , Mo Jialin , Liu Fei , Deng Kaiwen , Wang Dongyang , Feng Zhaoyang , Jiang Yifei , Li Yanong , Ma Yuting , Liu Zijia , Li Meiyu , Tian Peiyi , Shi Yanfeng , Jiang Yong , Yang Tao , Li Shouwei , Liang Jianfeng , Wu Jingchuan , Wang Ying , Zou Wanjing , Jiang Yina , Wang Lusheng , Chen Fang , Jin Xin , Li Shuaicheng , Qiu Xiaoguang , Li Chunde , Gao Ya , Tang Yujie , Taylor Michael D , Jiang Tao
Published: February 2025

Background

Despite numerous studies on medulloblastoma (MB) cell heterogeneity, the spatial characteristics of cellular states remain unclear.

Methods

We analyze single-nucleus and spatial transcriptomes and chromatin accessibility from human MB spanning four subgroups, to identify malignant cell populations and describe the spatial evolutionary trajectories. The spatial CNVs patterns and niches were analyzed to investigate the cellular interactions.

Results

Three main malignant cell populations were identified, including progenitor-like, cycling and differentiated populations. Gene signatures of cell populations strongly correlate to clinical outcomes. These tumor cell populations are geographically organized as stem-like and mature regions, highlighting their spatially heterogeneous nature. Progenitor-like and cycling cells are mainly concentrated in stem-like regions, whereas various differentiated populations are primarily distributed in mature regions. By analyzing chromosomal alterations, we find that stem-like region typically harbors a single pattern of CNVs, reflecting high originality and uniformity, which is in stark contrast to mature region exhibiting multiple patterns with a broader range of biological functions. Projecting cellular state program onto spatial sections fully illustrates the evolution from stem-like region to various functional zones in mature region, which is correlated to microenvironmental components along the paths to maintain stemness or promote differentiation. Conclusions. This multi-omics database comprehensively facilitates the understanding of MB spatial evolutionary organization.
Autoantibodies targeting angiotensin‐converting enzyme 2 are prevalent and not induced by SARS‐CoV‐2 infection
Authors: Galipeau Yannick , Castonguay Nicolas , McCluskie Pauline S. , Sonoda Mayra Trentin , Keeshan Alexa , Collins Erin , Arnold Corey , Pelchat Martin , Burns Kevin , Cooper Curtis , Langlois Marc‐André
Published: February 2025

Clinical outcomes resulting from SARS‐CoV‐2 infection vary widely, ranging from asymptomatic cases to the development of mild to severe respiratory illness, and in some instances, chronic lingering disease and mortality. The underlying biological mechanisms driving this wide spectrum of pathogenicity among certain individuals and demographics remain elusive. Autoantibodies have emerged as potential contributors to the severity of COVID‐19. Although preliminary reports have suggested the induction of antibodies targeting Angiotensin‐Converting Enzyme II (ACE2) post‐infection, this assertion lacks confirmation in large‐scale studies. In this study, our objective is to comprehensively characterize and quantify the prevalence and expression levels of autoantibodies directed against ACE2 in a sizable cohort (n = 464). Our findings reveal that ACE2‐reactive IgM antibodies are the most prevalent, with an overall seroprevalence of 18.8%, followed by IgG at 10.3% and IgA at 6.3%. Longitudinal analysis of individuals with multiple blood draws showed stable ACE2 IgG and IgA levels over time. Upon stratifying individuals based on molecular testing for SARS‐CoV‐2 or serological evidence of past infection, no significant differences were observed between groups. Functional assessment of ACE2 autoantibodies demonstrated that they are non‐neutralizing and failed to inhibit spike‐ACE2 interaction or affect the enzymatic activity of ACE2. Our results highlight that ACE2 autoantibodies are prevalent in the general population and were not induced by SARS‐CoV‐2 infection in our cohort. Notably, we found no substantiated evidence supporting a direct role for ACE2 autoantibodies in SARS‐CoV‐2 pathogenesis.
Effects of Middle Ear Status on Rotary Chair Outcomes in Children
Authors: Vicente Manuel , El-Hidek Nour , Patterson Jessie N. , Merchant Gabrielle R. , Janky Kristen L.
Published: February 2025

Objective:

Middle ear dysfunction is common in young children. There are varying reports on the effects of middle ear dysfunction on the vestibular system; however, it is unknown the extent to which abnormal middle ear function affects vestibular function tests, which could lead to misdiagnosis and improper medical management. Therefore, the purpose of this study is to evaluate how middle ear status affects rotary chair outcomes in young children (6 months to 6 years).

Design:

Twenty-one children with middle ear dysfunction (mean: 30 months, 11 males) and 36 control children with normal middle ear function (mean: 33 months, 19 males) participated. All participants completed tympanometry, wideband tympanometry, and sinusoidal harmonic acceleration rotary chair testing at 0.01, 0.04, and 0.16 Hz. The primary outcomes were rotary chair gain, phase, and symmetry.

Results:

For rotary chair gain, there was a significant frequency by group interaction. As expected, gain increased with increases in frequency; however, there were larger gain increases in the middle ear dysfunction group for 0.04 and 0.16 Hz. There was no significant effect of middle ear dysfunction on rotary chair phase or symmetry. Although 6 subjects (29%) had rotary chair phase leads that were greater than 2 SDs from the control mean, there were no significant group-level differences in phase; there was also no effect of severity of middle ear dysfunction on any rotary chair outcomes.

Conclusions:

Rotary chair in the presence of middle ear dysfunction is valid; however, isolated phase abnormalities can be present that are not explained by severity of middle ear dysfunction. Tympanometry and/or wideband tympanometry is recommended before rotary chair. In the event phase abnormalities are present coupled with abnormal tympanometry and/or wideband tympanometry, rotary chair testing could be repeated once the middle ear normalizes to rule out contributions from middle ear dysfunction.
Iruplinalkib for G1202R-mutant non–small cell lung cancer with anaplastic lymphoma kinase double fusion failed to alectinib: a case report
Authors: Yang Guangjian , Hu Jiaqi , Liu Runze , Li Pei , Yang Linke , Tang Xiaoyong , Wang Luokun
Published: February 2025

The novel and highly selective anaplastic lymphoma kinase (ALK) inhibitor iruplinalkib showed potent activity and manageable safety profiles in patients with ALK-rearranged non–small cell lung cancer (NSCLC). However, the evidence of iruplinalkib for uncommon ALK double fusion and secondary G1202R resistance mutation is limited. Here, we report a case of a 36-year-old male with metastatic NSCLC harboring uncommon TTC7A-ALK and EML4-ALK double fusion. Alectinib as first-line therapy showed partial response, with a progression-free survival (PFS) of 20 months. When his disease progressed, the ALK secondary G1202R resistance mutation was identified. His metastatic paraesophageal lymph node decreased during iruplinalkib treatment, achieving an ongoing PFS benefit for 10 months. Treatment-related adverse events of iruplinalkib were grade 1 hypercholesterolemia and hypertriglyceridemia. The modeling simulation revealed that the G1202R mutation exerted little effect on the binding of iruplinalkib. Iruplinalkib showed potency to G1202R because of its unique chemical structure and removal of steric clashes, which might be a promising option for ALK-rearranged NSCLC patients with G1202R resistance mutation.
Patterns of expression and prognostic implication of glycoprotein nonmetastatic protein B (GPNMB) expression in sentinel lymph nodes of melanoma patients
Authors: Beitner Ariel , Abu-Abeid Adam , Dayan Danit , Gat Andrea , Miodovnik Mor , Levy Carmit , Nizri Eran
Published: February 2025

Sentinel lymph node biopsy (SLNB) is a critical procedure in the management of melanoma, offering prognostic information and guiding adjuvant therapy. Glycoprotein nonmetastatic melanoma protein B (GPNMB), a melanogenesis marker, has been implicated in melanoma progression. This study investigates the expression patterns of GPNMB in SLN metastases and their association with oncological outcomes. We conducted a retrospective analysis of 27 melanoma patients with positive SLNB at Tel Aviv Sourasky Medical Center between 2010 and 2020. Immunohistochemistry was used to assess GPNMB expression in SLN metastases, categorizing patients into two groups based on GPNMB expression patterns: homogeneous (GPNMBho) and margin high (GPNMBmh). Peri-tumoral CD8+ T cell infiltration was also evaluated. Clinical outcomes, including melanoma-specific survival (MSS) and disease-free survival (DFS), were analyzed. GPNMB expression in SLN metastases displayed two distinct patterns: uniform (GPNMBho) and high at the tumor margins (GPNMBmh). Patients in the GPNMBmh group had significantly more peri-tumoral CD8+ T cells and exhibited improved MSS (127.6, 95% CI: 111.7–143.5 vs 79.5, 95% CI: 48.2–110.9 months, P = 0.018) and DFS (107.5, 95% CI: 79–135.8 vs 38, 95% CI: 15.2–60.8 months, P = 0.04) compared to the GPNMBho group. Multivariate analysis confirmed that GPNMB expression pattern and lymph node metastasis size were independent predictors of both MSS and DFS. GPNMB expression patterns in SLN metastases are strongly associated with long-term oncological outcomes in melanoma patients. The GPNMBmh pattern, characterized by higher margin expression and increased CD8+ infiltration, may serve as a prognostic biomarker for recurrence if validated in larger cohorts.
Characteristics of Eyes with Asymptomatic Primary Angle Closure Glaucoma with Varying Severity of Visual Field Loss at Presentation
Authors: Umapathi Ruthra M. , Hliang Tin Nwe , Su-Min Audrey Koh , Sim Charmaine , Perera Shamira A. , Husain Rahat , Ho Ching Lin , Wong Tina T. , Aung Tin , Nongpiur Monisha E.
Published: February 2025

Précis:

Approximately 38% of 467 asymptomatic primary angle closure glaucoma subjects had severe visual field loss (<−20 dB) at first presentation. Gender-based differences in prevalence and biometry suggests the need for an integrated approach for assessing risk.

Purpose:

To compare the clinical characteristics of patients with asymptomatic primary angle-closure glaucoma (PACG) across varying disease severity at presentation.

Methods:

Of 681 PACG patients recruited, 196 were excluded due to acute primary angle-closure and 18 due to pre-treatment. Clinical data from 467 patients were analysed, including age at presentation, presenting intraocular pressure (IOP), pre-intervention gonioscopy, vertical cup-to-disc ratio, biometry, pre-surgery refractive data, and visual field (VF) mean deviation (MD) at presentation (excluding the first VF). Disease severity was classified based on the VF MD as early-to-moderate (≥−12 dB), advanced (−12.01 to −20 dB), and severe (<−20 dB).

Results:

Of the 467 patients, 304 had reliable VFs within 1.5 years of presentation and were categorized as early-to-moderate (n=129; 42.4%), advanced (n=57; 18.8%) and severe PACG (n=118; 38.8%). Mean age at presentation was 64.7±8.6 years and 52.6% were male. Patients with severe PACG were more likely to be male (61.9%), with the highest presenting IOP (P<0.001), and narrowest anterior chamber angle (P<0.001). Significantly smaller anterior chamber depth and shorter axial length across worsening disease severity were only observed in female but not in male subjects. There was no significant difference in mean age at presentation across groups (P=0.12). Presenting IOP of ≤21 mm Hg was observed in 49.1% (n=28) advanced and 29.7% (n=35) severe PACG.

Conclusions:

Similar age at presentation of severe PACG and those with less severe disease suggests that the severe group either developed PACG at an earlier age or underwent rapid disease progression. Gender-based differences of prevalence and biometry may also impact disease risk.
Orthotic Interventions in Children’s and Adolescent’s Lower-Limb Transverse Plane Rotational Malalignments (A Systematic Review)
Authors: Keshavarzi Fatemeh , Baghaei Roshanak , Aliannejad Yeganeh , Rezaei Sina
Published: February 2025

Introduction

Lower-limb malalignments in children and adolescents can lead to future issues like arthritis. Surgery is not usually recommended for mild cases, and many parents do not prefer it for moderate conditions. Effective orthotic interventions may offer a promising alternative to address both mild and moderate malalignments.

Objective

The study aims to investigate the relationship between patient characteristics, orthosis type, and outcome variables in orthotic intervention studies for children with lower-limb rotational malalignment.

Study Design

This study is a systematic review.

Methods

Based on the search strategy developed by authors, five electronic databases including Web of Science, Scopus, PubMed, CINAHL Complete-EBSCO, and Cochrane Library were screened from 2000 to September 2023. All studies with orthotic interventions or shoe modification for children with lower-limb rotational malalignment without neurologic disorders or any other special disease were eligible. There was a restriction for the year of publication. The PEDdro scale was used for quality assessment.

Results

Five electronic databases revealed the 1999 documents. After screening the title and abstract, 10 studies were included in this review based on the full text. One thousand children with in-toeing gait patterns but different etiologies of abnormal gait took part in the 10 included studies.

Conclusions

Evidence supports the effect of the gait plate on the foot progression angle of in-toeing gait caused by excessive tibial torsion or femoral anteversion. Nighttime braces can be effective in the management of in-toeing gait caused by internal torsion of the tibia. The twister brace may affect the gait in the increased femoral anteversion condition. We suggest that future studies focus on evaluating the mechanism of orthoses function based on in-toeing gait etiology.

Clinical Relevance

By prescribing orthoses according to the underlying cause of rotational deformity, it is possible to enhance gait parameters and bone structure. Nighttime bracing may be beneficial for children with rotational deformities caused by tibial torsion; gait plate and twister orthoses have the potential to enhance walking patterns in both children and adolescents who have excessive hip anteversion.
Association between Islamic religiosity and preoperative anxiety in liver and renal transplant patients: a single-centered study from Pakistan
Authors: Khattak Umme Kulsoom , Hameed Muddsar , Ahmer Hania , Sajid Samaha , Khan Afridi Sheraz
Published: February 2025

Introduction:

This study investigates the association between religiosity and preoperative anxiety in liver and renal transplant patients at a tertiary care hospital in Pakistan. This study aims to explore the association between Islamic religiosity and preoperative anxiety in liver and renal transplant patients at a tertiary care hospital in Islamabad.

Objectives:

It seeks to assess preoperative anxiety levels in both donors and recipients, examine the relationship between religiosity and preoperative anxiety, and investigate the role of religiosity as a coping mechanism in managing preoperative anxiety.

Methods:

Conducted on 140 patients over 2 years using non-probability convenience sampling and validated tools, significant associations were found between anxiety levels and gender, marital status, age, education, spouse occupation, and transplant type.

Results:

Older adults and liver transplant recipients reported higher anxiety. Significant correlations were found between transplant type and anxiety age differences in anxiety (F(3,136) = 4.5, P < 0.05) and anesthesia anxiety (F(3,136) = 6.6, P < 0.05). Liver transplant recipients reported higher anxiety than donors. Religious coping strategies, such as seeking Allah’s guidance, were linked to lower anxiety, particularly among liver transplant recipients.

Conclusion:

The study found that demographic factors such as age, gender, marital status, and transplant type significantly influence anxiety levels. Older adults and liver transplant recipients experienced higher levels of anxiety. Notably, religious coping strategies, including seeking Allah’s guidance, were associated with lower anxiety, especially among liver transplant recipients. The findings suggest that religiosity may serve as a valuable coping mechanism and highlight the need for further research on spiritual interventions in transplant care.
Impact of HLA Epitope Matching on Outcomes in Haploidentical HSCT With Distinct GVHD Prophylaxes
Authors: Iwasaki Makoto , Kanda Junya , Tanaka Hidenori , Ikegame Kazuhiro , Shindo Takero , Kawase Takakazu , Yoshihara Satoshi , Doki Noriko , Nakamae Hirohisa , Eto Tetsuya , Tanaka Takashi , Ara Takahide , Hiramoto Nobuhiro , Kondo Yukio , Matsuoka Ken-Ichi , Ando Toshihiko , Shono Katsuhiro , Nagafuji Koji , Fukuda Takahiro , Ichinohe Tatsuo , Atsuta Yoshiko , Murata Makoto , Morishima Satoko
Published: February 2025

Background.

The introduction of posttransplant cyclophosphamide (PTCy) for prophylaxis against graft-versus-host disease (GVHD) has led to an increase in the number of transplants from haploidentical donors. Accordingly, we aimed to understand the impact of HLA epitope mismatch on the outcomes of haploidentical hematopoietic stem cell transplantation (HSCT) with prophylaxis against GVHD.

Methods.

This retrospective study included 1037 patients who underwent their first HSCT for hematologic malignancies from haploidentical peripheral blood donors in a Japanese registry between 2011 and 2019. In total, 542 patients received PTCy and 495 received antithymocyte globulin-based GVHD prophylaxis.

Results.

In patients with high-risk disease who received PTCy, higher class I Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE-I) scores were associated with a significantly lower risk of relapse, leading to a higher overall survival (OS: high PIRCHE-I patients compared with low PIRCHE-I patients: relapse: hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.46-0.98; P = 0.040; mortality: HR, 0.69; 95% CI, 0.46-0.99; P = 0.042). In patients with standard-risk disease who received antithymocyte globulin, a significant association between class II PIRCHE (PIRCHE-II) and a lower incidence of nonrelapse mortality (NRM) leading to higher OS was observed (high PIRCHE-II patients compared with low PIRCHE-II patients, NRM: HR, 0.41; 95% CI, 0.19-0.86; P = 0.019; OS: HR, 0.55; 95% CI, 0.32-0.94; P = 0.030).

Conclusions.

These findings suggest the differential effects of T-cell epitope matching based on GVHD prophylaxis after haploidentical HSCT. Pretransplant disease status may also be important for understanding the graft-versus-leukemia effect of mismatched HLA in haploidentical HSCT using PTCy.