bluuebunny/crossref_metadata_2025 huggingface dataset:
Water-mediated ribonucleotide–amino acid pairs and higher-order structures at the RNA–protein interface: analysis of the crystal structure database and a topological classification
Authors: Jangra Raman , Trant John F , Sharma Purshotam
Published: December 2024

Water is essential for the formation, stability and function of RNA–protein complexes. To delineate the structural role of water molecules in shaping the interactions between RNA and proteins, we comprehensively analyzed a dataset of 329 crystal structures of these complexes to identify water-mediated hydrogen-bonded contacts at RNA–protein interface. Our survey identified a total of 4963 water bridges. We then employed a graph theory-based approach to present a robust classification scheme, encompassing triplets, quartets and quintet bridging topologies, each further delineated into sub-topologies. The frequency of water bridges within each topology decreases with the increasing degree of water node, with simple triplet water bridges outnumbering the higher-order topologies. Overall, this analysis demonstrates the variety of water-mediated interactions and highlights the importance of water as not only the medium but also the organizing principle underlying biomolecular interactions. Further, our study emphasizes the functional significance of water-mediated interactions in RNA–protein complexes, and paving the way for exploring how these interactions operate in complex biological environments. Altogether, this understanding not only enhances insights into biomolecular dynamics but also informs the rational design of RNA–protein complexes, providing a framework for potential applications in biotechnology and therapeutics. All the scripts, and data are available at https://github.com/PSCPU/waterbridges.
Human introns contain conserved tissue-specific cryptic poison exons
Authors: Margasyuk Sergey , Kuznetsova Antonina , Zavileyskiy Lev , Vlasenok Maria , Skvortsov Dmitry , Pervouchine Dmitri D
Published: December 2024

Eukaryotic cells express a large number of transcripts from a single gene due to alternative splicing. Despite hundreds of thousands of splice isoforms being annotated in databases, it has been reported that the current exon catalogs remain incomplete. At the same time, introns of human protein-coding (PC) genes contain a large number of evolutionarily conserved elements with unknown function. Here, we explore the possibility that some of them represent cryptic exons that are expressed in rare conditions. We identified a group of cryptic exons that are similar to the annotated exons in terms of evolutionary conservation and RNA-seq read coverage in the Genotype-Tissue Expression dataset. Most of them were poison, i.e. generated an nonsense-mediated decay (NMD) isoform upon inclusion, and many showed signs of tissue-specific and cancer-specific expression and regulation. We performed RNA-seq in A549 cell line treated with cycloheximide to inactivate NMD and confirmed using quantitative polymerase chain reaction that seven of eight exons tested are, indeed, expressed. This study shows that introns of human PC genes contain cryptic poison exons, which reside in conserved intronic regions and remain not fully annotated due to insufficient representation in RNA-seq libraries.
A phase Ib study evaluating the c-MET inhibitor INC280 (capmatinib) in combination with bevacizumab in patients with high-grade glioma
Authors: Falchook Gerald S , Battiste James D , Kalra Amandeep , Shastry Mythili , Finney Lindsey , Hoekstra Susan J , Shih Meredith G , Shih Kent C
Published: December 2024

Background

To improve survival in patients with high-grade glioma, INC280 (capmatinib) a highly selective and potent oral inhibitor of the MET receptor with robust central nervous system (CNS) penetration, was evaluated in combination with bevacizumab (BEV).

Methods

There were 2 phases, dose-escalation (3+3 design) and dose-expansion, which included patients (1) who progressed during or after first-line therapy (no prior BEV), (2) who progressed during or after second-line therapy with BEV, and (3) who had unresectable high-grade glioma (no prior BEV).

Results

Sixty-four patients with high-grade glioma were treated; 18 in escalation cohorts and 46 in expansion Cohorts A (21), B (15), and C (10). The maximum-tolerated dose (MTD) was not reached and the RP2D was 400 mg capmatinib PO BID (800 mg daily). Treatment continued for a median of 14 weeks and up to ~6 years in one patient. Common treatment-related adverse events (65% ≤ Grade 2) included fatigue, peripheral edema, nausea, diarrhea, ALT increased, and constipation. Headaches and seizures occurred in 11 patients; Grade 3+ events included Grade 3 headache (1) and Grade 3 seizures (4). There were no treatment-related deaths. The 12 responders to treatment (2 CRs [1 pt in escalation and 1 pt in Cohort A] and 10 PRs [2 pts in escalation and A = 6, B = 1, and C = 1]) had a median duration of response of 9.2 months. Two patients with durable responses (CR >5 years, PR >1 year) did not harbor baseline c-MET alterations.

Conclusion

Capmatinib + BEV was well-tolerated but had no clear signal of activity in c-MET non-activated high-grade glioma.
Can We Predict Who Will Experience Adverse Events While Using Smoking Cessation Pharmacotherapy? A Secondary Analysis of the EAGLES Clinical Trial
Authors: Wolf Bethany J , Gray Kevin M , Dahne Jennifer R , Hashemi Daniel , Tomko Rachel L
Published: December 2024

Introduction

Concerns about potential side effects remain a barrier to uptake of Food and Drug Administration-approved smoking cessation pharmacotherapy (ie, varenicline, bupropion, nicotine replacement therapy [NRT]). However, use of pharmacotherapy can double the odds of successful quitting. Knowledge of an individual’s likelihood of side effects while taking smoking cessation pharmacotherapy could influence treatment planning discussions and monitoring.

Methods

We conducted a secondary, post hoc analysis to predict an individual’s likelihood of adverse events (AEs) using the Evaluating Adverse Events in a Global Smoking Cessation Study data from 4209 adults in the United States who smoked. Participants were randomized to receive 12 weeks of treatment with varenicline, bupropion, NRT patch, or placebo. Our models predicted the likelihood of moderate to severe psychiatric and nonpsychiatric AEs during treatment.

Results

Using pretreatment demographic and clinical data, multivariable logistic regression models yielded acceptable areas under the receiver operating characteristic curve for an individual’s likelihood of moderate to severe (1) psychiatric AEs for bupropion and NRT and (2) nonpsychiatric AEs for varenicline and bupropion. Once we adjusted for demographic and baseline characteristics, medication was not associated with psychiatric AEs. Varenicline differed from placebo with regards to nonpsychiatric AEs.

Conclusions

It is possible to predict person-specific likelihood of moderate to severe psychiatric and nonpsychiatric AEs during smoking cessation treatment, though the probability of psychiatric AEs did not differ by medication. Future work should consider factors related to implementation in clinical settings, including determining whether lower burden assessment protocols can be equally accurate for AE prediction.

Implications

Using data from a large dataset people who smoke in the United States, it is possible to predict an individual’s likelihood of psychiatric and nonpsychiatric AEs during smoking cessation treatment prior to initiating treatment. These predictive models provide a starting point for future work addressing how best to modify and integrate such clinical decision support algorithms into treatment for smoking cessation.
Improving recruitment to occupational health professions through highlighting intrinsic rewards
Authors: Semkina A , Norrie C , Elaswarapu R , Kessler I , Moriarty J , Boaz A , Manthorpe J , Knight A
Published: December 2024

Background

There are currently 2.5 million people economically inactive in the UK due to sickness. The government is considering a range of new initiatives to bring them back into the workforce; however, a lack of occupational health (OH) professionals, who play an important part in the recovery of physical and mental conditions that would otherwise inhibit employees from working, is hindering these efforts.

Aims

To identify factors that make OH attractive as a source of employment with the aim of assisting those undertaking recruitment to the specialism.

Methods

We conducted a qualitative study comparing the views of 13 OH nurses and doctors (‘insiders’) and 45 students and professionals from other medical and nursing fields (‘outsiders’) across the UK. Both groups provided their perceptions about what makes OH an attractive career. Data collection involved a mix of interviews and focus groups conducted from March to July 2023. Transcripts were thematically analysed using NVivo 14 to manage the data.

Results

Both groups highly valued the work-life balance offered by OH work, which represents a positive point of attraction to employment. In addition, people working in OH talked extensively about more intrinsic rewards—the opportunity to be impactful, to enjoy job variety and to practise preventative approaches.

Conclusions

The intrinsic rewards that OH work brings need to be advertised more widely to attract potential recruits who are ‘a good fit’ to OH and will be committed to the field.
Dengue pancreatitis with ketoacidosis—a rare manifestation in Endemicity
Authors: Das Kalyan Kumar , Basu Rajdeep
Published: December 2024

Dengue may begin as a straightforward fever episode with or without rash also it may affect some organs and cause serious symptoms. Although it is uncommon, severe abdominal discomfort has been a concerning indicator of acute pancreatitis. We report on a male patient, age 26, who first presented with fever, vomiting, and stomach pain. Later, he developed severe pancreatitis. When an acute viral infection causes pancreatitis, ketoacidosis can occur without hyperglycemia. We emphasize that in dengue patients reporting stomach pain, it is important to rule out acute pancreatitis (AP), an uncommon but serious impediment in the course of treatment.
Linezolid induced acute toxic leukoencephalopathy and severe thrombocytopenia presenting as stroke mimic—a case report
Authors: Ahmed S , Hayman G , Moin S , Ubaide H , Sivakumar R , Padayatty J
Published: December 2024

A 67-year-old lady was admitted with, right sided weakness and right arm shaking. She had recently completed a course of Linezolid for a diabetic foot infection and osteomyelitis. Prior to this she had prodromal symptoms including lethargy and loss of appetite. Clinical features prompting presentation included global weakness, verbal dysfluency and visual disturbance. MRI brain showed bilateral alteration of signal in the deep white matter of the posterior frontal and parietal lobes, sparing the superficial cortical areas. These areas showed diffusion restriction, suggestive of, but not limited to, ischaemic stroke. During admission she had a decline in consciousness and was hypertensive. An acute drop in haemoglobin and platelets occurred prompting consideration of Thrombotic Microangiopathy and other drug related/malignant/infective aetiologies. A diagnosis of Linezolid induced Acute Toxic Leukoencephalopathy and thrombocytopenia was made based on clinico-radiographic features and exclusion of other causes.
Host responses to haustorium invasion of the stem parasitic plant, Cuscuta campestris, differ from responses to wounding
Authors: Park Jihwan , Yamamoto Shota , Tsushima Ayako , Aoki Koh
Published: December 2024

The parasitic mechanism employed by the stem parasitic plant, Cuscuta campestris, involves degradation of the host epidermis and intrusion of the cortical tissue of the host stem by a specialized organ called the haustorium. In host plants, the mechanical stimuli associated with this degradation and intrusion of host tissues is considered to be comparable to wounding. However, it has not yet been clarified whether parasitic invasion and wounding induce equivalent responses in host plants. In this study, we demonstrated that parasitic intrusion-induced responses that were comparable to wounding in the host plant, Arabidopsis thaliana, including upregulation of Arabidopsis NAC DOMAIN-CONTAINING PROTEIN 71 (ANAC071), which is a key transcription factor associated with wound repair, cell division, and vascular development. Despite these similarities, we found that the mechanism regulating the induction of cell division- and vascular development-related genes at the host–parasite interface differed from that associated with wound repair. Specifically, ANAC071 was not required for the induction of cell division-related genes, as their upregulation was observed in anac071/096/011 triple mutants as well as in wild-type host plants. We also found that neither auxin nor ethylene plays a significant role in inducing the expression of vascular development-related genes. Thus, the findings show that the mechanisms responsible for upregulating cell division- and vascular development-related genes differ between parasitic and wound repair responses.
The DENSE AND ERECT PANICLE1-GRAIN NUMBER ASSOCIATED module enhances rice yield by repressing CYTOKININ OXIDASE 2 expression
Authors: Zhang Jinhui , Lin Qibing , Wang Xin , Shao Jiale , Ren Yulong , Liu Xin , Feng Miao , Li Shuai , Sun Qi , Luo Sheng , Liu Bojuan , Xing Xinxin , Chang Yanqi , Cheng Zhijun , Wan Jianmin
Published: December 2024

The phytohormone cytokinin (CK) positively regulates the activity of the inflorescence meristem (IM). Cytokinin oxidase 2/Grain number 1a (OsCKX2/Gn1a)-mediated degradation of CK in rice (Oryza sativa L.) negatively regulates panicle grain number, whereas DENSE AND ERECT PANICLE 1 (DEP1) positively regulates grain number per panicle (GNP). However, the detailed regulatory mechanism between DEP1 and OsCKX2 remains elusive. Here, we report the GRAS (GIBBERELLIN ACID INSENSITIVE, REPRESSOR OF GA1, and SCARECROW) transcription factor GRAIN NUMBER ASSOCIATED (GNA), previously thought to be involved in the Brassinosteroids (BRs) signaling pathway, directly inhibits OsCKX2 expression in the IM through a DEP1-GNA regulatory module. Overexpressing GNA leads to increased CK levels and consequently higher branch number, GNP, and yield. Both DEP1 and dep1 enhance the inhibitory effect of GNA on OsCKX2 expression through interacting with GNA. GNA promotes the translocation of DEP1 to the nucleus, while the gain-of-function mutant dep1 translocates into the nucleus in the absence of GNA. Our findings provide insight into the regulatory mechanism underlying OsCKX2 and a strategy to improve rice yield.
A tissue-specific rescue strategy reveals the local roles of autophagy in leaves and seeds for resource allocation
Authors: Marmagne Anne , Chardon Fabien , Masclaux-Daubresse Céline
Published: December 2024

Autophagy is a vesicular mechanism that plays a fundamental role in nitrogen remobilization from senescing leaves to seeds. The Arabidopsis (Arabidopsis thaliana) autophagy (atg) mutants exhibit early senescence, reduced biomass, and low seed yield. The atg seeds also exhibit major changes in N and C concentrations. During plant development, autophagy genes are expressed in the source leaves and in the sink seeds during maturation. We thus addressed the question of whether the seed composition defects in atg mutants are caused by defective N remobilization from source leaves or whether they are due to the absence of autophagy in seeds during maturation. To answer this question, we restored autophagy activity in the atg5 mutant by expressing the wild-type (WT) ATG5 allele specifically in source leaves using the senescence-associated gene 12 (SAG12) promoter or specifically in seeds using the Glycinin-1 promoter, or in both organs using both constructs. In atg5, N remobilization from the rosettes to seeds was almost completely reestablished when transformed with the pSAG12::ATG5 construct. However, transformation with the pSAG12::ATG5 construct only partially restored seed composition. In contrast, seed N and C composition was largely restored by transformation with the pGly::ATG5 construct, even though the early leaf senescence phenotype was maintained in the atg5 background. Cotransformation with pSAG12::ATG5 and pGly::ATG5 completely restored the WT remobilization and seed composition phenotypes. Our results highlight the essential role of autophagy in leaves for nitrogen supply and in seeds for the establishment of carbon and nitrogen reserves.
The transcription factor VvMYB44-1 plays a role in reducing grapevine anthocyanin biosynthesis at high temperature
Authors: Leng Xiangpeng , Li Chen , Wang Peipei , Ren Yiran , Chen Jianqing , Liu Guangchao , Hakeem Abdul , Liu Yuting , Shi Xiaoya , Hou Ting , Haider Muhammad Salman , Liu Gengsen , Fang Jinggui
Published: December 2024

High temperature reduces anthocyanin accumulation in various horticultural plants. However, the molecular mechanisms underlying the high-temperature-induced reduction of anthocyanin in grape (Vitis vinifera) remain poorly understood. In this study, VvMYB44-1 was identified as a transcriptional repressor of anthocyanin biosynthesis in grape berries, and its gene expression was strongly induced by high-temperature treatment. Overexpression of VvMYB44-1 inhibited anthocyanin accumulation in both grape berries and tobacco (Nicotiana tabacum) by repressing the transcription of the anthocyanin biosynthesis genes dihydroflavonol-4-reductase (VvDFR) and UDP-glucose flavonoid-3-O-glucosyltransferase (VvUFGT). Furthermore, the interaction between VvMYB44-1 and VvWDR2 competitively inhibited the formation of the MYB-bHLH-WD40 (MBW) activation complex and weakened the transcriptional activity of the complex, thereby decreasing anthocyanin accumulation. Additionally, VvMYB44-1 facilitated cytokinin (CK) accumulation by upregulating the expression of the CK synthesis gene lonely guy 8 (VvLOG8) and inhibiting the CK degradation gene CK oxidase 4(VvCKX4), thus contributing to CK-mediated anthocyanin inhibition in grape berries. Moreover, the inhibitory effect of VvMYB44-1 on anthocyanin biosynthesis and its downstream target genes was weakened with the deletion of the ethylene-responsive element binding factor-associated amphiphilic repression (EAR) motif, indicating that the EAR motif is indispensable for the inhibitory effect of VvMYB44-1 on anthocyanin biosynthesis in grapes. These results provide insights into the regulatory network of VvMYB44-1 in high-temperature-mediated anthocyanin biosynthesis in grapes.
A novel mechanism of microbial attachment: The flagellar pump of Giardia lamblia
Authors: Picou Theodore J , Luo Haibei , Polackwich Robert J , Gabilondo Beatriz B , McAllister Ryan G , Gagnon David A , Powers Thomas R , Elmendorf Heidi G , Urbach Jeffrey S
Published: December 2024

The ability of microbes to attach to biological and inert substrates is a necessary prerequisite for colonization of new habitats. In contrast to well-characterized mechanisms that rely on specific or nonspecific chemical interactions between microbe and substrate, we describe here an effective hydrodynamic mechanism of attachment that relies on fluid flow generated by the microbe. The microbe Giardia lamblia, a flagellated protozoan parasite, naturally attaches to the microvilliated surface of the small intestine but is also capable of attaching indiscriminately to a wide range of natural and artificial substrates. By tracking fluorescent quantum dots, we demonstrate a persistent flow between the parasite and substrate generated by a pair of Giardia flagella. Using both experimental measures and computational modeling, we show that the negative pressure generated by this fluid flow is sufficient to generate the previously measured force of attachment. We further show that this dynamically generated negative pressure allows Giardia to attach to both solid and porous surfaces, thereby meeting the real-world demands of attachment to the microvilliated surface of intestinal cells. These findings provide experimental support for a hydrodynamic model of attachment that may be shared by other ciliated and flagellated microbes.
Uncertainty quantification in coupled wildfire–atmosphere simulations at scale
Authors: Schwerdtner Paul , Law Frederick , Wang Qing , Gazen Cenk , Chen Yi-Fan , Ihme Matthias , Peherstorfer Benjamin
Published: December 2024

Uncertainties in wildfire simulations pose a major challenge for making decisions about fire management, mitigation, and evacuations. However, ensemble calculations to quantify uncertainties are prohibitively expensive with high-fidelity models that are needed to capture today’s ever-more intense and severe wildfires. This work shows that surrogate models trained on related data enable scaling multifidelity uncertainty quantification to high-fidelity wildfire simulations of unprecedented scale with billions of degrees of freedom. The key insight is that correlation is all that matters while bias is irrelevant for speeding up uncertainty quantification when surrogate models are combined with high-fidelity models in multifidelity approaches. This allows the surrogate models to be trained on abundantly available or cheaply generated related data samples that can be strongly biased as long as they are correlated to predictions of high-fidelity simulations. Numerical results with scenarios of the Tubbs 2017 wildfire demonstrate that surrogate models trained on related data make multifidelity uncertainty quantification in large-scale wildfire simulations practical by reducing the training time by several orders of magnitude from 3 months to under 3 h and predicting the burned area at least twice as accurately compared with using high-fidelity simulations alone for a fixed computational budget. More generally, the results suggest that leveraging related data can greatly extend the scope of surrogate modeling, potentially benefiting other fields that require uncertainty quantification in computationally expensive high-fidelity simulations.
Development and Validation of the Barriers to Professional Self-Care Scale (BPS-CS)
Authors: Rodríguez-Ramos Paulo Adrián , Aguilera-Ávila Laura , Gonzalez-Mendez Rosaura
Published: December 2024

Professionals who provide essential social services often face high levels of stress and the suffering of others. Self-care is key to preventing the negative consequences of these working conditions, but it is mostly defined as a personal responsibility. This individualist interpretation may contribute to exacerbating the costs of work stress by ignoring the existence of barriers that do not depend on the professionals. This study aims to develop and validate a new instrument to assess barriers to self-care among social workers, as well as their association with self-compassion and self-care practices. The sample comprised 325 social workers from Spain. Participants were predominantly female (87.4 percent) and worked in public social services (52 percent). Confirmatory factor analysis revealed a four-factor structure (“lack of information,” “self-care is unprofessional,” “self-care is not a priority,” and “noninvolvement of organizations”) consisting of 17 items with adequate psychometric properties. Considering self-care to be unprofessional was associated with less involvement in self-care practices. The social workers who considered the barriers to be more limiting were also those who reported more uncompassionate responses. The Barriers to Professional Self-Care Scale can be used to identify the barriers to professionals’ self-care, examining what maintains them and advancing in its prevention.
In vitro human ion channel assays predictive of drug-induced seizure
Authors: Cohen Jennifer D , You Dahea , Sharma Ashok K , Takai Takafumi , Hara Hideto , Sales Vicencia T , Yukawa Tomoya , Cai Beibei
Published: December 2024

Seizure is among the most severe FDA black box warnings of neurotoxicity reported on drug labels. Gaining a better mechanistic understanding of off-targets causative of seizure will improve the identification of potential seizure risks preclinically. In the present study, we evaluated an in vitro panel of 9 investigational (Cav2.1, Cav3.2, GlyRA1, AMPA, HCN1, Kv1.1, Kv7.2/7.3, NaV1.1, Nav1.2) and 2 standard (GABA-A, NMDA) ion channel targets with strong correlative links to seizure, using automated electrophysiology. Each target was assessed with a library of 34 preclinical compounds and 10 approved drugs with known effects of convulsion in vivo and/or in patients. Cav2.1 had the highest frequency of positive hits, 20 compounds with an EC30 or IC30 ≤ 30 µM, and the highest importance score relative to the 11 targets. An additional 35 approved drugs, with categorized low to frequent seizure risk in patients, were evaluated in the Cav2.1 assay. The Cav2.1 assay predicted preclinical compounds to cause convulsion in nonclinical species with a sensitivity of 52% and specificity of 78%, and approved drugs to cause seizure in nonclinical species or in patients with a sensitivity of 48% or 54% and specificity of 71% or 78%, respectively. The integrated panel of 11 ion channel targets predicted preclinical compounds to cause convulsion in nonclinical species with a sensitivity of 68%, specificity of 56%, and accuracy of 65%. This study highlights the utility of expanding the in vitro panel of targets evaluated for seizurogenic activity, in order to reduce compound attrition early on in drug discovery.
Value of EUS-guided through-the-needle biopsy in the diagnosis of pancreatic cystic neoplasms: An 8-year experience
Authors: Cheng Bingqian , Du Chen , He Zhengting , Feng Xiuxue , Li Huikai , Wang Zhanbo , Gao Fei , Zhao Yunyun , Chai Ningli , Linghu Enqiang
Published: December 2024

Background and Objectives

An accurate diagnosis is crucial for the clinical management of pancreatic cystic neoplasm (PCN). EUS-guided through-the-needle biopsy (EUS-TTNB) is a novel technique for improving the accuracy of PCN diagnosis. There is insufficient evidence about the efficacy of EUS-TTNB. This study aims to evaluate the feasibility and diagnostic performance of EUS-TTNB for PCN.

Methods

Between June 2015 and July 2023, we prospectively enrolled 454 patients with a clinical concern for PCN in our database. After excluding those diagnosed with pancreatic cancer, pseudocysts, or other no-neoplasms, we assessed 326 patients with 329 cysts undergoing EUS-guided fine-needle-aspiration (EUS-FNA) or EUS-TTNB for evaluation. The primary indicators were tissue acquisition yield and diagnostic yield. The cyst characteristics (size, location, the presence of septation, mural nodule, and solid mass) and the number of biopsy samples were chosen for the analysis of factors associated with diagnostic performance.

Results

There were 220 (67.5%) females and 106 (32.5%) males, and the median patient age was 50 years (range, 18–88). There were 329 cysts sampled by FNA and 143 by TTNB. The median cyst size was 31.5 mm (range, 6.9–114.0). The diagnostic yields of FNA and TTNB were 35.7% (112/314) and 57.5% (73/127), respectively (P < 0.001). Special cyst types were diagnosed by TTNB in 58 (45.7%, 58/127) cysts, 19 of which had surgical pathology. Fifteen of 19 TTNB diagnoses were concordant with the surgical pathology.

Conclusion

EUS-TTNB is an option to improve the diagnosis of PCN. Standardized procedures and appropriate indications for TTNB need to be studied.
Choroidal Hyperreflective Foci as Biomarkers of Severity in Stargardt Disease
Authors: Lee Seo Yoon , Yoon Chang Ki , Park Un Chul , Park Kyu Hyung , Lee Eun Kyoung
Published: December 2024

Purpose:

To investigate the clinical implications of choroidal hyperreflective foci (HF) as biomarkers of disease severity in Stargardt disease (STGD).

Methods:

129 eyes from 66 patients with STGD were included. The primary outcome was the correlation between the number of foveal choroidal HF and indicators of disease severity. Secondary outcome included a comparison of choroidal HF between the pathological and healthy borders of atrophy, and the two-year longitudinal change of foveal choroidal HF.

Results:

Long disease duration, thin central macular thickness, large definitely decreased autofluorescence area, atrophic foveal retinal pigment epithelium (RPE), high Fishman stage, and low visual acuity were associated with a higher number of foveal choroidal HF. Foveal RPE involvement (β = 0.522, p < 0.001) was the most strongly correlated factor in multivariate analysis. Genotype-phenotype relationships between the number of severe ABCA4 variants and choroidal HF could not be determined. The pathological border had significantly more choroidal HF than the healthy border (p < 0.001), and the number of foveal choroidal HF increased over two years (p = 0.003).

Conclusion:

Choroidal HF could serve as a biomarker of disease severity in STGD, correlating with various severity indicators and especially reflecting the presence of RPE atrophy.
Vitreous Cytokine Profile in an Eye with a Vasoproliferative Tumor
Authors: Cobbs Lucy V. , Kaiser Alexis , Mundae Rusdeep , Shields Carol L. , Wald Kenneth J. , Modi Yasha
Published: December 2024

Purpose:

We present a patient with a primary vasoproliferative tumor (VPT) accompanied by vitreous haze and an epiretinal membrane (ERM). We report for the first time the vitreous cytokine profile from an eye with a primary VPT to explore the relationship between intraocular inflammation and these tumors.

Methods:

Retrospective chart review of a single patient case.

Results:

25-gauge pars plana vitrectomy with membrane peel and vitreous biopsy was performed. Peripheral vitreous shave exposed an inferior grey-red mass located at the ora serrata, consistent with VPT. Treatment with confluent, long duration endolaser was performed. Vitreous cytology was negative for malignancy. A 13-cytokine panel (Associated Regional and University Pathologists, Inc. Laboratories, Salt Lake City, UT) revealed elevated interleukin 6 (13.3 pg/mL; normal <=2.0) and interleukin 8 (6.0 pg/mL; normal <=3.0). At one month post-operative, visual acuity improved from 20/40 to 20/25 OD, with mild anterior vitreous inflammation and regression of the VPT.

Conclusion:

Pro-inflammatory and pro-angiogenic cytokines were elevated in the vitreous of this patient’s eye with a primary VPT. We suggest that the endothelial cells and macrophages which comprise VPTs could secrete these cytokines into the vitreous, resulting in vitreous haze and an overzealous fibrotic response manifested as ERM formation.
Initial Pre-exposure Prophylaxis Messaging Source Influences Pre-exposure Prophylaxis Use Among Older Adults: A Quantitative Survey of Older Adults in Columbus, Ohio
Authors: Albright Nathaniel , Morrison-Beedy Dianne , Morgan Ethan
Published: December 2024

Older adults account for one in every five new HIV infections in the United States yet are often overlooked in tailored pre-exposure prophylaxis (PrEP) messaging. The aim of this study was to evaluate the original PrEP messaging source and its influence on PrEP use among a cohort of older adults. The Columbus Health Aging Project data (N = 794) were used to examine the initial PrEP information source and PrEP use in the past 6 months, adjusting for demographics and sexually transmitted infection (STI) status. Forty-six percent reported an STI, and 11.5% used PrEP. The main sources of PrEP information were peers (42.2%) and health care providers (40.2%); media (17.6%) sources were less common. Compared with those who received PrEP information from their health care provider, those informed by peers (adjusted odds ratio [aOR] = 0.58; 95% confidence interval [CI]: 0.34–0.99) or media (aOR = 0.17; 95% CI: 0.07–0.42) were less likely to use PrEP. Adjusting for STI-, media-informed remained less likely to have used PrEP compared with those informed by providers (aOR = 1.14; 95% CI: 0.55–2.35). These findings highlight the importance of tailored PrEP messaging for older adults for Ending the HIV Epidemic efforts. Media appears less impactful as a messaging approach for older adults.
Efficacy of mHealth-Based Workplace Health Promotion Strategy in Improving Cardiorespiratory Fitness in a Healthcare Setting
Authors: Ghazala Syed , Veluswamy Sundar Kumar , Ravindra Savita , Arena Ross , Myers Jonathan
Published: December 2024

Objective

This study aimed to test the efficacy of a mHealth-based workplace health promotion strategy in improving cardiorespiratory fitness in a healthcare setting.

Methods

Seventy-seven female nurses (age, 30–45 years) meeting the inclusion criteria underwent baseline assessment and received either a 12-week mHealth or awareness intervention based on their workplace. Changes in peak oxygen consumption (VO2), fasting blood sugar, and physical activity were compared within and between the groups at the end of the intervention.

Results

Thirty-seven and 33 participants in the mHealth and awareness arms, respectively, completed the 12-week intervention. Peak VO2 (1.6 mL/kg/min, 7%), physical activity, and step counts improved significantly in the mHealth arm. However, between-group differences were not significant.

Conclusions

mHealth interventions offer unique opportunities to improve physical activity and cardiorespiratory fitness among health professionals in their workplace.
Incidence of Neoplasms in Endemic Fight Agents
Authors: Bastos Maria Luiza Almeida , de Carvalho Thalyta Gleyane Silva , Batista Maxmiria Holanda , Ferreira Marcelo José Monteiro
Published: December 2024

Objective

The aim of the study is to measure cancer’s incidence in endemic fight agents in a Brazil’s Northeast state.

Methods

This is a historical cohort with 1053 endemic fight agents. A survival analysis was performed using Kaplan-Meier method.

Results

The overall neoplasm incidence rate has been 5508 cases per 105, and 4843 cases per 105 when nonmelanoma skin tumors were excluded. The increase in incidence of neoplasms occurred in 2019 and has conferred a risk of neoplasms 20 times higher than the national and state incidence.

Conclusions

We believe in an occupational factor for these results: the chronic exposure to insecticides used in public health campaigns. The peak incidence of neoplasms, in 2019, may corroborate with long induction period of these compounds, in addition to consistency with specialized literature.
Echocardiography Findings for Pulmonary Hypertension During Workup for Bronchoscopic Lung Volume Reduction
Authors: Mahajan Amit K. , Collar Nancy , Muldowney Frances , Gorka Paul , Duong Duy K. , Patel Priya P. , Cicenia Joseph , Hogarth Douglas K. , Nathan Steven
Published: December 2024

Bronchoscopic lung volume reduction (BLVR) is a minimally invasive intervention that improves dyspnea and quality of life in select individuals with emphysema. Echocardiography is the initial screening tool for pulmonary hypertension (PH) in patients evaluated for BLVR. Multiple BLVR and lung volume reduction surgery (LVRS) trials have used and right ventricular systolic pressure (RVSP) of 45 mm Hg as a cutoff for potential significant PH. However, PH is established hemodynamically by right heart catheterization (RHC), not echocardiography due to notoriously inaccurate RSVP values in patients with lung disease, especially those with COPD and suboptimal acoustic imaging windows. Over a 5-year period, all patients who met PFT criteria for BLVR underwent a routine screening echocardiogram for PH. Twenty-four patients with a RVSP >45 mm Hg or suspicion of significant PH on echocardiography were subjected to RHC. Twenty-one (88%) with suspicion for significant PH based on echocardiography did not have significant PH on RHC. Three patients (12%) had significant PH based on RHC precluding them from BLVR. Ten of the 21 patients with echo suspected PH, but RHC negative PH qualified for BLVR. Twelve-month follow-up data was available for 7 of these patients post-BLVR that included change in forced expiratory volume in 1 second (FEV1), 6-minute walk distance (6MWD), and St. George’s Respiratory Questionnaire (SGRQ). The mean change in FEV1 showed an increase of 0.154 L, 6MWD increase of 42 m, and SGRQ decrease of 11.5 points. On the basis of results from this study, all patients being evaluated for BLVR found to have a RVSP over 45 mm Hg on echocardiography should undergo RHC to confirm significant PH.
Coping With Anticipatory Grief: A Qualitative Study of Parents of Children With Advanced Cancer
Authors: Ng Yong Hao , Fu Fang
Published: December 2024

Background

Anticipatory grief is a common but understudied phenomenon among parents of children with advanced cancer. Appropriate coping with anticipatory grief may promote better adaptation before and after the death.

Objective

To explore the anticipatory grief experiences and coping approaches of such parents in Shanghai, China.

Methods

Using Husserlian phenomenology approach, 4 fathers and 16 mothers were interviewed at the Children’s Medical Center in Shanghai. The transcripts were analyzed using Colaizzi phenomenological methods.

Results

Five themes were developed. The first theme described anticipatory grief experiences characterized by trauma and chronic misery, and the next 4 themes described how the parent coped with the grief through avoidance, acceptance, hope, and being present-focused. Parents coped differently at different times—from diagnosis, the time while the child was on treatment, to the time the parents could consider the possibilities of an uncertain future. The study also found that coping with grief is an intrapersonal and interpersonal process.

Conclusion

The study offers insights into parents’ dynamic coping processes when living with grief. Nurses could play a critical role in facilitating this process of living with grief.

Implications for Practice

Oncology nurses, by understanding parents’ anticipatory grief, can align themselves with the parents’ coping processes to provide appropriate support.
Plateau hypoxia-induced upregulation of reticulon 4 pathway mediates altered autophagic flux involved in blood–brain barrier disruption after traumatic brain injury
Authors: Dong Xinning , Xu Jing , Du Kejun , Chen Xin , Shu Haifeng , Yu Sixun
Published: December 2024

This study aimed to examine reticulon 4 (RTN4), neurite outgrowth inhibitor protein expression that changes in high-altitude traumatic brain injury (HA-TBI) and affects on blood–brain barrier’s (BBB) function. C57BL/6J 6–8-week-old male mice were used for TBI model induction and randomized into the normal altitude group and the 5000-m high-altitude (HA) group, each group was divided into control (C) and 8h/12h/24h/48h-TBI according to different times post-TBI. Brain water content (BWC) and modified Neurological Severity Score were measured, RTN4 and autophagy-related indexes (Beclin1, LC3B, and SQSTM1/p62) were detected by western blot, immunofluorescence technique, and PCR in peri-injury cortical tissues. The expression of NgR1, Lingo-1, TROY, P75, PirB, S1PR2, and RhoA receptors’ downstream of RTN4 was detected by PCR. HA-TBI caused increased neurological deficits including motor, sensory, balance and reflex deficits, increased BWC, earlier peak RTN4 expression and a longer duration of high expression in peri-injury cortical tissues, and enhanced levels of Beclin1, LC3B, and SQSTM1/p62 to varying degrees. Concurrently, the transcription of S1PR2 and PirB, the main signaling molecules downstream of RTN4, was significantly increased. In HA-TBI’s early stages, the increased RTN4 may regulate enhanced autophagic initiation and impaired autolysosome degradation in vascular endothelial cells via S1PR2 receptor activation, thereby reducing BBB function. This suggests that autophagy could be a new target using RTN4 intervention as a clinical HA-TBI mechanism.
Diabetes may contribute to cognitive impairment in Parkinson’s disease via damaging white matter tracts
Authors: Liu Zhihui , Wei Jiahao , Su Huahua , She Yuchen , Wang Junyi , Liu Ying , Mo Lijuan , Tan Changhong , Liu Xi , Chen Lifen
Published: December 2024

Parkinson’s disease with dementia (PDD) severely affects the quality of life of patients with Parkinson’s disease (PD) in the later stages. Recently, PD patients with diabetes were found to have a higher risk of cognitive decline and developing dementia with a faster progression, but the underlying mechanism remains unclear. Diabetes-related white matter damage may partially explain the mechanism by which diabetes participates in PDD. Seventy PD patients were included. PD patients underwent diffusion tensor imaging from The Second Affiliated Hospital of Chongqing Medical University were collected and were divided into four groups: PD with diabetes without dementia, PD with dementia without diabetes, PD without dementia and diabetes. Tract-based spatial statistics analysis and region-of-interest-based analysis were performed. Factorial analysis with diabetes and dementia taken as the main effects was performed, and the differences between the white matter fibers of PD patients from the four groups were also analyzed. The interaction between diabetes and dementia in the damage of white matter in PD patients was also analyzed. We found that both diabetes and dementia were found to be related to the damage in internal capsule, corona radiata, and thalamic radiation of the PD patients. There is an interaction between diabetes and dementia in the white matter damage of PD patients. Both diabetes and dementia were found to be related to the damage in internal capsule, corona radiata, and thalamic radiation of the PD patients. Diabetes may participate in cognitive decline in PD patients via damaging cognition-related white matter tracts.
Climate geroscience: the case for ‘wisdom-inquiry’ science
Authors: Farrelly Colin
Published: December 2024

Why should, and how can, the fields of climate science and geroscience (which studies the biology of ageing) facilitate the cross-disciplinary collaboration needed to ensure that human and planetary health are both promoted in the future of an older, and warmer, world? Appealing to the ideal of ‘wisdom-oriented’ science (Maxwell 1984 In
From knowledge to wisdom: a revolution in the aims and methods of science
), where scientists consider themselves to be artisans working for the public good, a number of the real-world epistemic constraints on the scientific enterprise are identified. These include communicative frames that stoke intergenerational conflict (rather than solidarity) and treat the ends of planetary and human health as independent ‘sacred values’ (Tetlock 2003
Trends Cogn. Sci.
7
, 320–324) rather than as
interdependent
ends. To foster ‘climate geroscience’—the field of knowledge and translational science at the intersection of climate science and geroscience—researchers in both fields are encouraged to think of novel ways they could make researchers from the other field ‘conversationally’ present when framing the aspirations of their respective fields, applying for grant funding and designing their conferences and managing their scientific journals.
Perspectives of La
0.9
Sr
0.1
Fe
0.9
Co
0.1
O

3±
δ

perovskite obtained by Pechini and sonochemical methods: a case study
Authors: de la Huerta-Hernández Gloria E. , Rodríguez-Flores Tatiana , Reyes-Montero Armando , Castro-Cisneros Iván , Hernández-Pérez Isaías , Chávez-Carvayar José A.
Published: December 2024

The sonochemical method is a novel synthesis route that takes advantage of the use of ultrasonic radiation to obtain different nanomaterials with an improvement in the process variables and material characteristics. In this work, two different synthesis routes to obtain a double perovskite structure were compared in detail. The Pechini synthesis method is a widely used and effective way to obtain this kind of structure by the formation of a cross-linked network of metal cations. Alternatively, in sonochemistry, chemical reactions occur with the application of powerful ultrasound radiation. The final characteristics of synthesized powders of La
0.9
Sr
0.1
Fe
0.9
Co
0.1
O
3±

δ

(LSFC) were analysed thermally, structurally, morphologically and optically, and their transport properties were evaluated to determine their semiconductor character in a solid oxide fuel cell device and in photocatalytic processes. Structural results indicated a well crystallized perovskite structure with a single cubic phase. The cell parameter
a
(approx. 3.89 Å) and crystal size measurements (11–20 nm) were determined by Rietveld refinement for samples obtained by both synthesis methods. Thescanning electron microscope micrographs showed aggregates with homogeneous morphology and a uniform particle size distribution, with a rough and porous surface. Optical properties were determined by ultraviolet–visible spectrophotometry and photoluminescence, resulting in an
E
g
of 1.2 and 0.8 eV in samples from Pechini and sonochemistry, respectively.
Genome assembly of the southern pine beetle (
Dendroctonus frontalis
Zimmerman) reveals the origins of gene content reduction in
Dendroctonus
Authors: Copeland Megan , Landa Shelby , Owoyemi Adekola Oluwatosin , Jonika Michelle M. , Alfieri James M. , Johnston J. Spencer , Sylvester Terrence Pradakshana , Kyre Bethany R. , Hoover Zachary , Hjelmen Carl E. , Rieske Lynne K. , Blackmon Heath , Casola Claudio
Published: December 2024

Dendroctonus frontalis
also known as southern pine beetle (SPB), is the most damaging insect forest pest in the southeastern United States. Genomic data are important to provide information on pest biology and to identify molecular targets to develop improved pest management approaches. Here, we produced a chromosome-level genome assembly of SPB using long-read sequencing data. Synteny analyses confirmed the conservation of the core Coleopteran Stevens elements and validated the
bona fide
SPB X chromosome. Transcriptomic data were used to obtain 39 588 transcripts corresponding to 13 354 putative protein-coding loci. Comparative analyses of gene content across 14 beetles and three other insects revealed several losses of conserved genes in the
Dendroctonus
clade and gene gains in SPB and
Dendroctonus
that were enriched for loci encoding membrane proteins and extracellular matrix proteins. While lineage-specific gene losses contributed to the gene content reduction observed in
Dendroctonus
, we also showed that widespread misannotation of transposable elements represents an important cause of the apparent gene expansion in several non-
Dendroctonus
species. Our findings uncovered distinctive features of the SPB gene complement and disentangled the role of biological and annotation-related factors contributing to gene content variation across beetles.
Interbreeding area movement of an adult humpback whale between the east Pacific Ocean and southwest Indian Ocean
Authors: Kalashnikova Ekaterina , Botero-Acosta Natalia , Duque Mesa Esteban , Gascón Mar Palanca , Lyne Patrick , Cheeseman Ted , Vogel Alex , Kennedy Amy , Akkaya Aylin
Published: December 2024

Humpback whales undertake one of the longest known migrations of any mammal. While their migration route generally extends between latitudes, the breeding stocks are longitudinally separated and display high site fidelity to their feeding grounds. While there is an indication of certain breeding stocks overlapping with each other, the current information on the migration routes of humpback whales within the Southern Hemisphere limits our understanding of the extent of this exchange. Presented here is the longest documented great-circle distance between sightings on wintering grounds of two different ocean basins of an adult male humpback whale, involving two breeding stocks in the eastern Pacific (stock G) and southwest Indian Ocean (stock C). These two stocks are separated by a minimum of 120° longitude, and a great-circle distance of 13 046 km. This extreme distance movement demonstrates behavioural plasticity, which may play an important role in adaptation strategies to global environmental changes and perhaps be an evolved response to various pressures, underlining the importance of consolidation of global datasets on wide-ranging marine mammals.