bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging of endogenous RNA in live cells using sequence-activated fluorescent RNA probes
Authors: Zheng Haifeng , Liu Xiyu , Liu Luhui , Hu Jiarui , Chen Xianjun
Published: December 2024

RNA performs a remarkable range of functions, such as RNA processing, chromosome maintenance and dosage compensation. Technologies that robustly and specifically image RNA in its native state are highly desirable, as these technologies can help researchers clarify the localization and functionality of diverse RNAs. Here, we describe the development of a sequence-activated fluorescent RNA (SaFR) technique. In SaFR, in the absence of target RNA, the structure of fluorogenic RNA is disrupted by the invader sequence, and the ability to activate the Pepper’s cognate fluorophores is lost as a result. In the presence of target RNA, SaFR undergoes conformational reorganization and transforms into the fluorogenic conformation of Pepper, enabling the activation of fluorophores to produce fluorescent signals. SaFR exhibits favourable properties, such as large dynamic ranges, high specificity and fast fluorescence generation. Further studies showed that exogenous or endogenous RNAs can be tracked in live and fixed cells through SaFR. We further demonstrated the usefulness of SaFR in monitoring the assembly and disassembly of stress granules in real-time. Overall, this study offers a robust and versatile tool for labelling and imaging endogenous RNA in cells, which will be useful for clarifying the functionality and molecular mechanism of RNA.
Hypoxia increases methylated histones to prevent histone clipping and heterochromatin redistribution during Raf-induced senescence
Authors: Chang Soojeong , Moon Ramhee , Nam Dowoon , Lee Sang-Won , Yoon Insoo , Lee Dong-Sung , Choi Seunghyuk , Paek Eunok , Hwang Daehee , Hur Junho K , Nam Youhyun , Chang Rakwoo , Park Hyunsung
Published: December 2024

Hypoxia enhances histone methylation by inhibiting oxygen- and α-ketoglutarate-dependent demethylases, resulting in increased methylated histones. This study reveals how hypoxia-induced methylation affects histone clipping and the reorganization of heterochromatin into senescence-associated heterochromatin foci (SAHF) during oncogene-induced senescence (OIS) in IMR90 human fibroblasts. Notably, using top-down proteomics, we discovered specific cleavage sites targeted by Cathepsin L (CTSL) in H3, H2B and H4 during Raf activation, identifying novel sites in H2B and H4. Hypoxia counteracts CTSL-mediated histone clipping by promoting methylation without affecting CTSL’s activity. This increase in methylation under hypoxia protects against clipping, reshaping the epigenetic landscape and influencing chromatin accessibility, as shown by ATAC-seq analysis. These insights underscore the pivotal role of hypoxia-induced histone methylation in protecting chromatin from significant epigenetic shifts during cellular aging.
The farnesoid X receptor activates transcription independently of RXR at non-canonical response elements
Authors: van der Veen Suzanne W , Dijkstra Jelmer J , Willemsen Ellen C L , Houtman René , Milona Alexandra , Marchet Nikolas , Spit Maureen , Hollman Danielle , Zwartkruis Fried J T , Vermeulen Michiel , Ramos Pittol Jose M , van Mil Saskia W C
Published: December 2024

The farnesoid X receptor (FXR) is a nuclear receptor (NR) known to obligately heterodimerize with the retinoid X receptor (RXR). FXR is expressed as four isoforms (α1–α4) that drive transcription from IR-1 (inverted repeat-1) response elements (REs). Recently, we found that FXR isoforms α2/α4 also activate transcription from non-canonical ER-2 (everted repeat-2) REs, mediating most metabolic effects of general FXR activation. Here, we explored molecular determinants of regulation by FXRα2 from ER-2 REs through quantitative interaction proteomics, site-directed mutagenesis and transcriptomics. We discovered FXRα2 binds to and activates ER-2 elements in vitro and in reporter assays independently of RXR. Genome-wide binding analysis in mouse liver revealed higher ER-2 motif enrichment in FXR sites lacking RXR. Abrogation of FXRα2:RXR heterodimerization abolished IR-1, but preserved ER-2 transactivation. Transcriptome-wide, RXR overexpression inhibited 25% of FXRα2 targets in HepG2. These genes were specifically activated by the heterodimerization-deficient mutant FXRα2L434R, enriched for ER-2 motifs at their promoters, and involved in lipid metabolism and ammonia detoxification. In conclusion, RXR acts as a molecular switch, inhibiting FXRα2 activation from ER-2 while enhancing it from canonical IR-1 REs. Our results showcase FXR as the first NR with isoform-specific RXR-independent REs, highlighting a new layer of regulation and complexity for RXR-heterodimerizing NRs.
The 2025 Nucleic Acids Research database issue and the online molecular biology database collection
Authors: Rigden Daniel J , Fernández Xosé M
Published: December 2024

The 2025 Nucleic Acids Research database issue contains 185 papers spanning biology and related areas. Seventy three new databases are covered, while resources previously described in the issue account for 101 update articles. Databases most recently published elsewhere account for a further 11 papers. Nucleic acid databases include EXPRESSO for multi-omics of 3D genome structure (this issue’s chosen Breakthrough Resource and Article) and NAIRDB for Fourier transform infrared data. New protein databases include structure predictions for human isoforms at ASpdb and for viral proteins at BFVD. UniProt, Pfam and InterPro have all provided updates: metabolism and signalling are covered by new descriptions of STRING, KEGG and CAZy, while updated microbe-oriented databases include Enterobase, VFDB and PHI-base. Biomedical research is supported, among others, by ClinVar, PubChem and DrugMAP. Genomics-related resources include Ensembl, UCSC Genome Browser and dbSNP. New plant databases cover the Solanaceae (SolR) and Asteraceae (AMIR) families while an update from NCBI Taxonomy also features. The Database Issue is freely available on the Nucleic Acids Research website (https://academic.oup.com/nar). At the NAR online Molecular Biology Database Collection (http://www.oxfordjournals.org/nar/database/c/), 932 entries have been reviewed in the last year, 74 new resources added and 226 discontinued URLs eliminated bringing the current total to 2236 databases.
Mechanistic insights into Sindbis virus infection: noncapped genomic RNAs enhance the translation of capped genomic RNAs to promote viral infectivity
Authors: Karki Deepa , LaPointe Autumn T , Isom Cierra , Thomas Milton , Sokoloski Kevin J
Published: December 2024

Alphaviruses are globally distributed, vector-borne RNA viruses with high outbreak potential and no clinical interventions, posing a significant global health threat. Previously, the production and packaging of both viral capped and noncapped genomic RNAs (cgRNA and ncgRNA) during infection was reported. Studies have linked ncgRNA production to viral infectivity and pathogenesis, but its precise role remains unclear. To define the benefits of ncgRNAs, pure populations of capped and noncapped Sindbis virus (SINV) gRNAs were synthesized and transfected into host cells. The data showed that mixtures of cgRNAs and ncgRNAs had higher infectivity compared to pure cgRNAs, with mixtures containing low cgRNA proportions exceeding linear infectivity expectations. This enhancement depended on co-delivery of cgRNAs and ncgRNAs to the same cell and required the noncapped RNAs to be viral in origin. Contrary to the initial hypothesis that the ncgRNAs serve as replication templates, the cgRNAs were preferentially replicated. Further analysis revealed that viral gene expression, viral RNA (vRNA) synthesis and particle production were enhanced in the presence of ncgRNAs, which function to promote cgRNA translation early in infection. Our findings highlight the importance of ncgRNAs in alphaviral infection, showing they enhance cgRNA functions and significantly contribute to viral infectivity.
Precision medicine: an intrahepatic cholangiocarcinoma with a novel RBPMS-MET fusion sensitive to crizotinib
Authors: Wan Wei , Liu Xueqin , Zhang Yamin , Shen Rui , Xia Weihu , Li Shuangni , Tan Yuan , Duan Qianqian , Liu Jinpeng , Wang Wuping
Published: December 2024

Background

Intrahepatic cholangiocarcinoma is a malignant tumor that starts from the epithelium of the bile duct and has a poor prognosis. They are characterized by poor response to chemotherapy and lack of effective targeted therapies; thus, therapeutic options are limited.

Case Presentation

A 59-year-old man was admitted to the hospital for a workup of abnormal CA19-9 levels. He was diagnosed with ICC, underwent surgery and was found to have pT1bNx disease. He developed rapid disease recurrence on adjuvant gemcitabine + capecitabine. Following recurrence, he received first-line systemic pembrolizumab + lenvatinib and second-line pembrolizumab + lenvatinib + chemotherapy and had mild tumor regression followed by progression. Next-generation sequencing was performed on the baseline surgical sample. This revealed a novel RBPMS-MET fusion, and based on the literature, crizotinib 250 mg twice a day was administered. After 3 months of crizotinib treatment, magnetic resonance imaging revealed a significant reduction in liver lesions, and 4 months after initiating treatment, scans demonstrated a partial response.

Conclusion

Our case report strengthens the evidence that crizotinib may be a viable treatment option for patients with ICC with a c-MET tyrosine kinase fusion, necessitating additional clinical investigation.
Associations of frailty with survival, hospitalization, functional decline, and toxicity among older adults with advanced non-small cell lung cancer
Authors: Lee Howard J , Boscardin John , Walter Louise C , Smith Alexander K , Cohen Harvey J , Giri Smith , Williams Grant R , Presley Carolyn J , Singhal Surbhi , Huang Li-Wen , Velazquez Ana I , Gubens Matthew A , Blakely Collin M , Mulvey Claire K , Cheng Michael L , Sakoda Lori C , Kushi Lawrence H , Quesenberry Charles , Liu Raymond , Fleszar-Pavlovic Sara , Eskandar Caroline , Cutler Edward , Mercurio Anne Marie , Wong Melisa L
Published: December 2024

Introduction

Among older adults with cancer receiving chemotherapy, frailty indices predict OS and toxicity. Given the increased use of immunotherapy and targeted therapy for advanced non-small cell lung cancer (aNSCLC), we evaluated frailty and Karnofsky Performance Status (KPS) among older adults with aNSCLC receiving chemotherapy, immunotherapy, and/or targeted therapy.

Methods

Patients aged ≥ 65 with aNSCLC starting systemic therapy with non-curative intent underwent geriatric assessments over 6 months. We developed a deficit-accumulation frailty index to categorize patients as robust, pre-frail, or frail. To evaluate associations between frailty and KPS with OS, we used Cox proportional hazards models adjusted for race, insurance, and treatment. We used logistic regression to evaluate hospitalizations, functional decline, and severe toxicity.

Results

Among 155 patients (median age 73), 45.8% were robust, 36.1% pre-frail, and 18.2% frail; 34.8% had a KPS ≥ 90, 32.9% had a KPS of 80, and 32.3% had a KPS ≤ 70. The median OS was 17.9 months. Pre-frail/frail patients had worse OS compared to robust patients (adjusted hazard ratio [HR] 2.09, 95% CI, 1.31-3.34) and were more likely to be hospitalized (adjusted odds ratio [OR] 2.21, 95% CI, 1.09-4.48), functionally decline (adjusted OR 2.29, 95% CI, 1.09-4.78), and experience grade ≥ 3 hematologic toxicity (adjusted OR 5.18, 95% CI, 1.02-26.03). KPS was only associated with OS.

Conclusions

Our frailty index was associated with OS, hospitalization, functional decline, and hematologic AEs among older adults with aNSCLC receiving systemic therapies, while KPS was only associated with OS. Pretreatment frailty assessment may help identify older adults at risk for poor outcomes to optimize decision-making and supportive care.
The BRAHMA-associated SWI/SNF chromatin remodeling complex controls Arabidopsis seed quality and physiology
Authors: Wrona Magdalena , Zinsmeister Julia , Krzyszton Michal , Villette Claire , Zumsteg Julie , Mercier Pierre , Neveu Martine , Sacharowski Sebastian P , Archacki Rafał , Collet Boris , Buitink Julia , Schaller Hubert , Swiezewski Szymon , Yatusevich Ruslan
Published: December 2024

The SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complex is involved in various aspects of plant development and stress responses. Here, we investigated the role of BRM (BRAHMA), a core catalytic subunit of the SWI/SNF complex, in Arabidopsis thaliana seed biology. brm-3 seeds exhibited enlarged size, reduced yield, increased longevity, and enhanced secondary dormancy, but did not show changes in primary dormancy or salt tolerance. Some of these phenotypes depended on the expression of DOG1, a key regulator of seed dormancy, as they were restored in the brm-3 dog1-4 double mutant. Transcriptomic and metabolomic analyses revealed that BRM and DOG1 synergistically modulate the expression of numerous genes. Some of the changes observed in the brm-3 mutant, including increased glutathione levels, depended on a functional DOG1. We demonstrated that the BRM-containing chromatin remodeling complex directly controls secondary dormancy through DOG1 by binding and remodeling its 3′ region, where the promoter of the long noncoding RNA asDOG1 is located. Our results suggest that BRM and DOG1 cooperate to control seed physiological properties and that BRM regulates DOG1 expression through asDOG1. This study reveals chromatin remodeling at the DOG1 locus as a molecular mechanism controlling the interplay between seed viability and dormancy.
Optimized single-cell gates for yeast display screening
Authors: Pan Xiaoli , de Souza Matheus O , Figueiras Francisco M , Huang Aric , Banach Bailey B , Wolfe Jacy R , Pirhanov Azady , Madan Bharat , DeKosky Brandon J
Published: December 2024

Yeast display is a widely used technology in antibody discovery and protein engineering. The cell size of yeast enables fluorescence-activated cell sorting (FACS) to precisely screen gene libraries, including for multi-parameter selection of protein phenotypes. However, yeast cells show a broader size distribution than mammalian cells that complicates single-cell gate determination for FACS. In this report, we analyze several yeast display gating options in detail and present an optimized strategy to select single yeast cells via flow cytometry. These data reveal optimized single-cell gating strategies to support robust and high-efficiency yeast display studies.
Cross-Subsidization of Bad Credit in a Lending Crisis
Authors: Artavanis Nikolaos , Lee Brian Jonghwan , Panageas Stavros , Tsoutsoura Margarita
Published: December 2024

We study the corporate-loan pricing decisions of a major, systemic bank during the Greek financial crisis. A unique aspect of our data set is that we observe both the actual interest rate and the “break-even rate” (BE rate) of each loan, as computed by the bank’s own loan-pricing department (in effect, the loan’s marginal cost). We document that low-BE-rate (safer) borrowers are charged significant markups, whereas high-BE-rate (riskier) borrowers are charged smaller and even negative markups. We rationalize this de facto cross-subsidization through the lens of a dynamic model featuring depressed collateral values, impaired capital-market access, and limit pricing.
A protocol for targeted B-lymphocyte depletion for the treatment of IgG4-related disease
Authors: Colquhoun Matthew , Barwick Tara D , Bolton Eva , Gibbons Norma , Hughes-Hallett Archie , Levy Jeremy B , McAdoo Stephen P , Parisinos Constantinos A , Philips Natalie , Tam Frederick W K , Wernig Florian , Youngstein Taryn , Tomlinson James A P
Published: December 2024

Objectives

To determine the clinical outcomes of patients with immunoglobulin 4-related disease (IgG4-RD) treated with a defined B-cell depletion protocol using rituximab.

Methods

Patients were included if they had (i) an IgG4-RD diagnosis at Imperial College Healthcare NHS Trust between February 2017 and October 2022, and (ii) >9 months of follow-up data available following the first rituximab dose. The rituximab protocol targeted B-cell depletion to <10 cells/microliter for a maintenance period of two years. Electronic records were used to define patient demographics, serological and radiological variables and treatment responses according to the IgG4-RD responder index (RI).

Results

Forty-five patients received induction treatment with rituximab. Two patients had insufficient follow-up data for outcome analysis. All patients responded to rituximab therapy according to the IgG4-RD RI. Most patients (25/43, 58%) were also treated with low-dose glucocorticoids at the time of rituximab induction (median prednisolone dose 5 mg daily) and 4/25 (16%) remained on prednisolone at two years (median prednisolone dose 5 mg daily). Disease flares occurred in 11/43 (26%) patients; 9/11 flares occurred in the presence of B-cell repopulation; 2/11 (18.1%) flares occurred in the absence of B-cell repopulation (>10 cells/uL). All flares re-treated with rituximab (7/7, 100%) responded positively.

Conclusion

Rituximab administration targeting B-cell depletion for a two-year period is an effective treatment strategy for IgG4-RD and can limit the cumulative glucocorticoid exposure. Flares are uncommon and typically occur in the setting of B-cell repopulation, with good clinical responses to further rituximab administration.
The effectiveness of revocable precommitment strategies in reducing decision-making impulsivity
Authors: Wang Dawei , Zhou Mengmeng , Han Dong , Wu Xiao , Mao Wenxu , Hu Yixin
Published: December 2024

Precommitment shows promise in reducing decision-making impulsivity; however, it may be invalidated, leading to self-control failures. Therefore, this study aimed to explore the effectiveness of revocable precommitment in promoting commitment and reducing decision-making impulsivity through two studies. Experiment 1 used event-related potentials to explore whether revocable precommitment was beneficial to make individuals more inclined to commit. Experiment 2 explored the effectiveness of revocable precommitment in reducing decision-making impulsivity. The results showed that (i) compared with the precommitment condition, there is a higher proportion of precommitment selection under the revocable precommitment condition. Besides, in short delay time condition, the proportion of individuals choosing precommitment is higher than that of the other two conditions. Additionally, the average amplitudes of N1 and P300 in the revocable precommitment condition are significantly lower than those in the precommitment condition. (ii) There is a higher proportion of choosing larger-later (LL) options in the revocable precommitment condition compared with the other conditions. Moreover, the proportion of choosing LL options in short-term conditions is higher than that in medium-term conditions, which is higher than that in long-term conditions. Our findings indicated the efficiency of revocable precommitment in reducing decision-making impulsivity.
“Not one of us”: anti-immigrant sentiment spread to multiple immigrant groups in the wake of Islamic terrorism
Authors: Ramirez Daniel , Kim Joeun
Published: December 2024

In reaction to terrorism, current research shows that discriminatory attitudes against immigrant populations among native populations sometimes increase. However, it is unclear if native populations respond to threats with a specifically targeted anti-immigrant sentiment or whether there is a general increase in anti-immigrant views that spill over to other minority groups. Furthermore, plausible processes explaining the spread of anti-immigration sentiment to larger immigrant populations are largely underexplored in the research. This article analyzes the impact of terrorist attacks on anti-Muslim sentiment and spillover effects on groups seemingly unrelated to the attacks. Using the coincidental timing of the European Social Survey and the attack on Charlie Hebdo, we investigate the effects of terrorism on anti-immigrant attitudes toward Muslim, Jewish, and Roma minorities. Second, in accordance with symbolic boundary theory, we investigate whether the Charlie Hebdo attack increased discriminatory attitudes toward immigrant characteristics and argue that these spillover effects are partially attributable to such changes. Our findings show that the Charlie Hebdo attack was associated with increased anti-immigrant sentiment toward all three groups to a comparable degree and that these effects are partially explained by intensified racial and religious boundaries. Furthermore, we find that the association between the attack and increases in racial and religious boundaries, as well as discriminatory attitudes toward all studied minorities, is stronger in countries with historically low immigration reception. Our study finds that where discriminatory processes are activated, they are not manifested through precise social categorization but rather using generalized minority characteristics.
Child Welfare Exhibitions in Delhi (1920, 1924–1932): Motherhood, Public Health and Colonial Government
Authors: Carballido-Coria Laura
Published: December 2024

The child welfare exhibitions in Delhi, held for the first time in 1920, and then from 1924 to 1932, aimed at educating mothers to look properly after their children hoping to reduce illness and mortality. These exhibitions are to be understood against two broad trends. One is a worldwide interest regarding maternal and infant mortality and a greater awareness regarding the relevance of hygiene and sanitation. The other is the set of particular concerns in India and Delhi. There was a shift in policy and language between the end of the decade of 1910 and the beginning of the decade of 1920, when sanitation acquired a new meaning which included not only drainage works or cleaning of streets, but also hygiene lessons and inspection at schools; when there was talk about public health, and greater emphasis on the role of the ‘Indian public’ and ‘social service’ in the colonial discourse.
Being a Woman Politician on the Isle of Man: How Smallness Explains Political Culture
Authors: Edge Peter W , Mackie Catriona , Powell Alex
Published: December 2024

This article explores the distinctive experience of women as legislators in a small democracy, drawing on a multimethod study of the Isle of Man. Experiences of gender in a small democracy’s politics are not merely quantitatively different, for instance in terms of constituents per representative; but qualitatively different as a result of the interconnected ramifications of quantitative differences. We find pervasive effects from the absence of strong party institutionalization, the intersection of intimacy and vulnerability, and the constraints of strictly limited capacity. Understanding gender and politics in a small democracy is an important contribution to island feminism, and acts as a corrective to an understanding of the interrelations of gender and politics within democratic constitutions based only on the experience of women in large democracies. The study also shows the pervasive importance of smallness even for a European democracy with close cultural ties to a large democracy.
Integrating Deep Learning Derived Morphological Traits and Molecular Data for Total-Evidence Phylogenetics: Lessons from Digitized Collections
Authors: Hunt Roberta , Reyes-Hernández José L , Shaw Josh Jenkins , Solodovnikov Alexey , Pedersen Kim Steenstrup
Published: December 2024

Deep learning has previously shown success in automatically generating morphological traits which carry a phylogenetic signal. In this paper we explore combining molecular data with deep learning derived morphological traits from images of pinned insects to generate total-evidence phylogenies and we reveal challenges. Deep learning derived morphological traits, while informative, underperform when used in isolation compared to molecular analyses. However, they can improve molecular results in total evidence settings. We use a dataset of rove beetle images to compare the effect of different dataset splits and deep metric loss functions on morphological and total evidence results. We find a slight preference for the cladistic dataset split and contrastive loss function. Additionally, we explore the effect of varying the number of genes used in inference and find that different gene combinations provide the best results when used on their own vs in total evidence analysis. Despite the promising nature of integrating deep learning techniques with molecular data, challenges remain regarding the strength of the phylogenetic signal and the resource demands of data acquisition. We suggest that future work focus on improved trait extraction and the development of disentangled networks to better interpret the derived traits, thus expanding the applicability of these methods in phylogenetic studies.
Emission patterns of volatile organic compounds from Norway spruce logs following bark beetle (Ips typographus L.) infestation
Authors: Du Baoguo , Frühbrodt Tobias , Delb Horst , Burzlaff Tim , Biedermann Peter H W , Kreuzwieser Jürgen
Published: December 2024

Norway spruce (Picea abies L.) is economically one of the most important conifer species in Europe. Spruce forests are threatened by outbreaks of the bark beetle Ips typographus L., and this will worsen with a projected warmer and drier climate and increased outbreak dynamic following storms. Volatile terpenes and aromatics play pivotal roles in defence of trees, however little is known about the emission dynamics of these compounds from trees colonized with I. typographus, particularly in dependence on the beetle’s developmental stages and colonization densities. Here, we analysed the emission profiles of volatile organic compounds (VOCs) from spruce logs colonized with low (LDT) and high (HDT) densities of I. typographus from the initial colonization until the emergence of the next beetle generation. A first VOCs emission peak appeared directly after colonization and lasted for 1 week. It mainly consisted of monoterpenoids and most likely reflected the trees’ constitutive defence against herbivory. Under HDT, a second emission maximum occurred during the larval stage, whereas under LDT a second peak appeared later during maturation feeding of callow beetles. In contrast to the first peak, sesquiterpenoids, aromatics and oxygenated monoterpenoids dominated the second peak, possibly reflecting the trees’ induced defence. Developing beetles seem to face a variety of defence compounds even if the tree has been overwhelmed and colonization by parental beetles was already successful. The specific release patterns under LDT and HDT might be due to different availability of precursor compounds, depletion of constitutively stored compounds and differences in microbial activities associated with the bark beetles. The present study highlights constitutive defence of spruce trees upon herbivore attack, and the effect of infestation density on the temporal dynamics of induced defence. Particularly the oxygenated monoterpenoid terpinen-4-ol may be used as cue to assess habitat quality and competition by newly arriving beetles.
Foliage development and resource allocation determine the growth responses of silver birch (Betula pendula) to elevated environmental humidity
Authors: Õunapuu-Pikas Eele , Tullus Arvo , Kupper Priit , Tamm Ilona , Reinthal Taavi , Sellin Arne
Published: December 2024

Scenarios for future climate predict an increase in precipitation amounts and frequency of rain events, resulting in higher air humidity and soil moisture at high latitudes, including in northern Europe. We analysed the effects of artificially elevated environmental humidity (air relative humidity and soil moisture) on leaf gas exchange, water relations, growth and phenology of silver birch (Betula pendula) trees growing at the free air humidity manipulation experimental site situated in the hemiboreal vegetation zone, in eastern Estonia, with no occurring water deficit to the trees. The environmental humidity manipulation did not significantly affect the water relations traits but did affect some leaf gas exchange parameters, growth and phenology of the trees. Elevated air humidity (H) did not influence photosynthetic capacity and stomatal conductance, while the trees exhibited higher stomatal sensitivity to leaf-to-air vapour pressure difference compared with the trees at ambient conditions (C) or at elevated soil moisture (I). H trees demonstrated reduced height growth and foliage biomass, increased allocation to stem radial growth and prolonged leaf retention in autumn compared with the C trees. Increased air humidity supports longer leaf retention and growth period, but this does not translate into increased growth parameters at the tree level. The changes in tree growth in response to increasing atmospheric humidity could plausibly be explained by (i) retardation of foliage development and (ii) changes in resource allocation, causing a shift in the ratio of photosynthetic to non-photosynthetic tissues in favour of the latter. Under high atmospheric evaporative demand, higher stomatal sensitivity in H trees induces faster stomatal closure, which may result in carbon starvation. A future rise in atmospheric humidity at high latitudes may lead to reduced tree growth and forest productivity, in contrast to the predicted future of forests.
γδ T cells in hematological malignancies: mechanisms and therapeutic strategies
Authors: Chen Xingchi , Sun Guangyu , Zhu Xiaoyu
Published: December 2024

γδ T cells are a unique subset of lymphocytes with both innate and adaptive features. They recognize and eradicate various hematological malignancies through different mechanisms, employing factors including γδ TCR, NKR, NKG2D, TRAIL, and perforin/granzyme. They also modulate other immune cells to enhance their antitumor activity. Moreover, γδ T cells have potent antiviral functions after hematopoietic stem cell transplantation (HSCT), which may improve the outcome of patients with hematological malignancies. In this review, we summarize the current knowledge on γδ T cell biology and function in hematological malignancies and HSCT complications. We also discuss the challenges and limitations of the clinical application of γδ T cells, such as their low frequency in peripheral blood and heterogeneity among different subsets. We then highlight some promising strategies for γδ T cell-based therapy, such as using agonist antibodies, cell engagers, or genetic modification technology. Furthermore, we review the recent clinical trials evaluating the safety and efficacy of γδ T-cell therapy in different hematological malignancies. In conclusion, γδ T cells represent a promising immunotherapeutic tool for hematological malignancies that deserves further exploration.
Lucio Phenomenon: a Review
Authors: Magaña Mario , Vargas Bornacini María Fernanda , Landeta-Sa Ana Paula , Aguilar-Mena Cristina
Published: December 2024

Mycobacterium leprae and M. lepromatosis, the causative agents of leprosy, have left a mark on human history. Despite advances in health care, leprosy continues to affect millions worldwide, often leading to complications, mostly neural, due to delayed diagnosis and treatment. This persisting prevalence emphasizes the need for continued research and effective management strategies. Leprosy presents in many forms, mainly lepromatous and tuberculoid, influenced by the patient's immunological status and exhibits specific clinical characteristics. Studies have shown that Mycobacterium lepromatosis is frequently associated with the lepromatous forms of the disease, characterized by generalized skin lesions and systemic involvement. This connection has led to the distinction of M. lepromatosis as the main cause of Lucio Leprosy and Lucio phenomenon (LPh); this last one is an immune-mediated response, including necrotizing panvasculitis and systemic manifestations. Once considered endemic to Mexico and Central America, migration expanded its geographical reach. Triggers include infections and certain medical conditions. Histopathologically, LPh represents a necrotizing panvasculitis, ischemic necrosis, and the presence of immune components in small vessels. Diagnosis relies on clinical characteristics and histopathological findings. Treatment lacks standardization; however, effective management involves antileprosy medication and systemic glucocorticoids. In conclusion, the historical impact of leprosy and LPh persists in medical discussions. Prevention, early diagnosis, and treatment challenges continue, necessitating ongoing research to improve patient outcomes and bring down this health concern.
Update on Absorbable Facial Thread Lifts
Authors: Riopelle Alexandria M. , Geisler Amaris N. , Eber Ariel , Dover Jeffrey S.
Published: December 2024

BACKGROUND

Thread lifts are a noninvasive technique for suspending ptotic skin. Previous studies have failed to show long-term efficacy data with absorbable threads.

OBJECTIVE

To review the recent literature evaluating mid and lower facial absorbable thread lifts over a four-year period from October 2018 to December 2022.

METHODS

A systematic review was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed database. Search terms included “lift,” “face lift,” “thread lift,” “suture suspension,” “silhouette suture,” “silhouette lift,” “rhytidectomy,” and “Aptos.” Technique articles with objective results were included.

RESULTS

Twelve studies met criteria for analysis (n = 818). The most common thread evaluated was suture suspension using polydioxanone followed by poly-l-lactic acid/polycaprolactone absorbable threads. Scores according to the Global Aesthetic Improvement Scale, Wrinkle Severity Scale, Barton's Grading System, and FACE-Q improved in all cases immediately after the procedure. The longest follow-up assessments were at 2 years. Complications were mild.

CONCLUSION

In the appropriate patient, thread lifts are immediately effective, and the risk of dangerous complications is low, but long-term efficacy data are lacking.
AI for Corneal Imaging: How Will This Help Us Take Care of Our Patients?
Authors: Redd Travis K.
Published: December 2024

As artificial intelligence continues to evolve at a rapid pace, there is growing enthusiasm surrounding the potential for novel applications in corneal imaging. This article provides an overview of the potential for such applications, as well as the barriers we must overcome to realize it.
Examining the Impact of an Intervention Designed to Improve National Physical Therapy Examination Performance Among Physical Therapist Education Program Graduates
Authors: Dombkowski Ryan , Sullivan Steven , Widenhoefer Tricia , Almonroeder Thomas Gus
Published: December 2024

Introduction.

National Physical Therapy Examination (NPTE) first-time pass rates are trending downward in recent years. As a result, there is a need for programs to identify ways to promote improved NPTE performance among their graduates.

Review of Literature.

Previous studies have identified factors that can be used to predict an individual's chances of passing the NPTE. However, to our knowledge, there are no published studies describing interventions designed to improve NPTE performance. The purpose of this study was to examine the impact of a novel intervention, which involved providing students with an individualized predicted NPTE score combined with faculty advising to support their NPTE preparation.

Subjects.

This study included members of 6 consecutive cohorts (190 total graduates) from an entry-level doctoral physical therapist education program.

Methods.

The members of the first 3 cohorts served as historical controls, while the final 3 cohorts received the intervention (experimental cohorts). The intervention involved using a regression model to predict students’ NPTE scores based on their prior academic performance. Faculty then shared these predicted scores with students and provided individualized advising to support their NPTE preparation. Regression analyses were conducted to compare NPTE performance for the control and experimental cohorts, while accounting for between-group differences in academic performance.

Results.

On average, the experimental cohorts performed 25.9 points higher on the NPTE and had over 5 times greater odds of passing the NPTE, compared to those in the control cohorts, after accounting for the covariates within the regression models.

Discussion and Conclusion.

Our intervention, which combined providing students with their predicted NPTE scores and faculty advising to support students’ NPTE preparation, was feasible to implement without requiring extensive additional resources. It appears that our novel intervention is a viable approach for promoting improved first-time NPTE performance.
Medication reconciliation in the outpatient primary care setting: Barriers and opportunities
Authors: Schriefer Susan P. , Ainslie Marcy
Published: December 2024

Increased complexity of the health care system has led to challenges of vital communications, such as a current and accurate patient medication list. Medication reconciliation aims to create the most comprehensive and accurate list of a patient's current medications by comparing it with their electronic health record. However, effectively gathering, organizing, and communicating this medication information across different stages of care is often complex and challenging. Fragmented provider groups and incompatible software systems can also lead to breaks in communication and contribute to medication discrepancies. Medication reconciliation is an evidence-based safety intervention that can decrease medication errors and patient harm. Primary care providers play a critical role in ensuring a patient's medication list is current and accurate.
Generation and characterization of zebrafish f9l mutant confirmed that f9l is f10 like gene
Authors: Dhinoja Sanchi , Mary Jabila , Qaryoute Ayah Al , De Maria Anthony , Jagadeeswaran Pudur
Published: December 2024

Aim

This study aimed to create an f9l mutant zebrafish using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) and characterize its coagulation properties to investigate its functional similarity to human FX and explore the potential synergy between f9l and f10.

Methods

Three gRNAs targeting exon 8 encoded by the catalytic domain of the f9l gene were injected into 300 single-cell zebrafish embryos using CRISPR/Cas9 technology. DNA from the resulting adults was extracted from tail tips, and PCR was used to detect indels. The identified founder mutant was bred to homozygosity, and functional assays, kinetic Russel viper venom time, bleeding assay in adults, and venous laser injury on larvae were conducted to assess its hemostatic function. Additionally, f10 was knocked down in f9l homozygous embryos using f10 antisense morpholinos to study their interaction by monitoring its survival.

Results

DNA from 60 adults was screened for indels, resulting in a fish with a heritable complex mutation involving one insertion and two deletions in exon 8. The f9l homozygous mutants exhibited impaired F10 activity, mild bleeding after mechanical injury, and developmental deformities in early larval stages. The caudal vein thrombosis assay showed variable occlusion times, indicating a bleeding phenotype with incomplete penetrance. Knocking down f10 in f9l homozygous embryos resulted in 50% mortality within five dpf, compared to f9l homozygous embryos injected with control morpholinos.

Conclusion

In summary, we generated f9l knockout and showed it is a paralog to f10. We also found a synergy between f9l and f10 genes, highlighting its importance in hemostasis.
Semiquantitative muscle parameters derived from FAPI and FDG PET/CT in evaluating sarcopenia among patients with malignant tumors
Authors: Chen Yang , Zhang Qing , Hu Yinting , Liu Entao , Tan Xiaoyue , Yuan Hui , Jiang Lei
Published: December 2024

Background

The objective of this study is to explore and compare the potential utility of fibroblast activation protein inhibitor (FAPI) and fluorodeoxyglucose PET/computed tomography (CT) in assessing sarcopenia among patients with malignant tumors.

Methods

A retrospective analysis was conducted on 127 patients with histologically confirmed malignant tumors who underwent both 18F/68Ga-FAPI and fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT scans. Clinical characteristics and PET/CT parameters of maximum and mean standard uptake value (SUVmax and SUVmean) of muscle at the 3rd lumbar (L3) level were reviewed. Skeletal muscle area at the L3 level was measured, and skeletal muscle index was calculated to determine sarcopenia. The association between sarcopenia and PET/CT parameters was analyzed.

Results

The incidence of sarcopenia was 41.7% among these 127 patients. Higher age, male, lower BMI, lower SUVmax and SUVmean of muscle from 18F/68Ga-FAPI PET/CT, and lower SUVmax of muscle from 18F-FDG PET/CT were correlated with a higher prevalence of sarcopenia (P < 0.05). Besides, no significant differences in SUVmax and SUVmean of muscle were noted between 18F-FAPI and 68Ga-FAPI groups. The best cutoff value of SUVmax of muscle from 18F/68Ga-FAPI PET/CT was 1.17, yielding the area under the curve (AUC) of 0.764 and sensitivity and specificity of 74.3% and 71.7%, while the optimal cutoff value of SUVmax of muscle from 18F-FDG PET/CT was 0.76, with an AUC of 0.642 and sensitivity and specificity of 36.5% and 86.8%, respectively.

Conclusion

Patients with sarcopenia exhibit decreased muscle uptake of FAPI and fluorodeoxyglucose. FAPI PET/CT emerges as a more valuable tool for sarcopenia assessment in patients with malignant tumors compared to fluorodeoxyglucose PET/CT.
Qualitative investigation into the functional problems of transtibial prostheses when amputees perform agricultural work
Authors: Ortega Bedoya Yessika María , Rendón Vélez Elizabeth , Mejía Londoño Valentina , Valencia Legarda Fanny , Plata Contreras Jesús Alberto
Published: December 2024

Background:

A significant number of Colombian farmers who are transtibial amputees are civilian victims of landmines. Current prostheses are inadequately adapted for agricultural work, resulting in functional challenges in this context.

Objective(s):

This study aims to analyze and categorize the functional problems of transtibial prostheses in the Colombian agricultural context, incorporating perspectives from prosthesis users, manufacturers, and designers.

Study Design:

Descriptive qualitative research involving 49 transtibial amputees using prostheses and 18 professionals engaged in prosthesis design, manufacture, or prescription.

Methods:

Participants were interviewed. Each interview was transcribed, and a conventional content analysis was conducted to identify functional problems with transtibial prostheses in agricultural settings.

Results:

Interviewees reported that sockets become loose from residual limbs, and soft sockets and socks are prone to damage and maladjustment. The prosthetic foot undergoes stress due to stiffness, causing cracks and accelerated deterioration. Fastening screws loosen, break, and rust, while cosmetic foam retains moisture, perforates, and deteriorates in sunlight. Prosthesis deterioration is exacerbated by weather, moisture, mud, tall grass, and uneven or sloping terrain.

Conclusions:

Prosthesis designs should facilitate sweat drainage or quick drying to address issues with soft sockets and socks. Sockets should be padded to minimize residual limb injuries. Durable, low-cost, and easily replaceable soft sockets are essential for farming environments. Additionally, farmers need a prosthetic foot that flexes when caught in brush or walking on uneven/inclined surfaces, allowing movement in two physiological planes without compromising strength and durability.
Fiberoptic Endoscopic Evaluation of Swallowing Function in Patients With Tumors Involving Both the Oral and Base of the Tongue
Authors: Zhu Yue , Qian Xiaoyun , Hou Lihao , Heng Weiwei , Sun Guowen
Published: December 2024

To investigate the clinical application of fiberoptic endoscopic evaluation of swallowing (FEES) and recovery of swallowing function in patients with lesions involving both the oral and base of the tongue (OBOT). Patients diagnosed with OBOT lesions underwent assessments preoperatively and at 1 week, 1 month, and 1 year postoperatively. The swallowing function evaluation included the MD Anderson Dysphagia Inventory (MDADI), University of Washington Quality-of-Life Questionnaire, Performance Status Scale for Head and Neck Cancer, water swallow test, tongue motion measurement, and FEES (a simple dysphagia score, and penetration–aspiration scale). Postoperative swallowing rehabilitation uses functional therapy. In total, 18 patients participated in this study. The FEES-based dysphagia score had high reliability and diagnostic value. FEES parameters were significantly correlated with results of the water swallow test and MDADI scores. At 1 year postoperatively, the swallowing function of patients with OBOT lesions returned to preoperative levels, although their quality of life was impacted. FEES is a reliable method for evaluating the postoperative swallowing function of patients with OBOT lesions and is worth clinically promoting. Although the swallowing function of these patients was restored, attention should be paid to the quality of life.
Extracapsular Dissection Versus Superficial Parotidectomy for Benign Parotid Tumors: A Bibliometric and Visual Analysis
Authors: Troise Stefania , Calabria Federica , Merola Raffaele , Calvanese Carlo , Arena Antonio , Abbate Vincenzo , Bonavolontà Paola , Dell'Aversana Orabona Giovanni
Published: December 2024

Utilizing data extracted from Scopus and Web of Science databases, all the publications comparing “Superficial Parotidectomy” AND “Extracapsular dissection” were considered. Original research, review articles, letters, and note articles were included. Data about publication frequency, language distribution, authorship patterns, co-occurrence of keywords, and citation counts were extracted. In addition, visual analysis techniques such as co-authorship, keyword co-occurrence and citation networks, and bibliographic coupling maps were employed to visualize relationships and patterns within the literature. From the Scopus database, a total of 152 records were identified and screened, resulting in the inclusion of 42 papers. The most cited paper (102 times) was published in Laryngoscope Journal. Bibliometric analysis of co-citation revealed 797 cited references and 1284 cited authors. From the Web of Science database, a total of 211 records were identified and screened, resulting in the inclusion of 28 papers. This study provides a deeper overview of the landscape surrounding the comparison between extracapsular dissection and superficial parotidectomy for benign parotid tumors and insights about research trends, collaboration patterns, and knowledge dissemination in this clinical area to facilitate evidence-based practice and guide future research.