bluuebunny/crossref_metadata_2025 huggingface dataset:
The sucrose signalling route controls Flavescence dorée phytoplasma load in grapevine leaves
Authors: Morabito Cristina , Pagliarani Chiara , Lovisolo Claudio , Ripamonti Matteo , Bosco Domenico , Marzachì Cristina , Roitsch Thomas , Schubert Andrea
Published: September 2024

Flavescence dorée (FD) is a phytoplasma disease transmitted by insects, causing severe damage in vineyards across Europe. Since there is no effective treatment, infected plants must be removed to prevent further spread. There is variation in susceptibility to FD among different grapevine cultivars, and some exhibit symptom remission, known as recovery, although the mechanisms behind this are unclear. Diseased plants accumulate soluble sugars, including sucrose, which influences the concentration of trehalose-6-phosphate (T6P), a signalling molecule affecting plant growth and stress responses. It is hypothesized that sucrose-mediated signalling via T6P could trigger defence mechanisms, reducing FD pathogen load and increasing plant recovery. To test this hypothesis, two grapevine genotypes with different susceptibility to FD were compared, revealing increased sucrose level and trehalose-6-phosphate synthase (TPS) activity in the more tolerant cultivar. However, FD-infected plants showed inhibited sucrose-cleaving enzymes and no activation of TPS expression. Attempts to enhance sucrose levels through trunk infusion and girdling promoted sucrose metabolism, T6P biosynthesis, and defence gene expression, facilitating symptom recovery. Girdling particularly enhanced T6P biosynthesis and expression of defence genes above the treatment point, reducing FD pathogen presence and promoting recovery. These findings indicate that elevated sucrose levels, possibly signalling through T6P, may limit FD pathogen spread, aiding in plant recovery.
Isotopic abundance of carbon in the DLA towards QSO B1331+170
Authors: Milaković Dinko , Webb John K , Molaro Paolo , Lee Chung-Chi , Jethwa Prashin , Cupani Guido , Murphy Michael T , Welsh Louise , D’Odorico Valentina , Cristiani Stefano , Génova Santos Ricardo , Martins Carlos J A P , Nunes Nelson J , Schmidt Tobias M , Pepe Francesco A , Zapatero Osorio Maria Rosa , Alibert Yann , González Hernández J I , Di Marcantonio Paolo , Palle Enric , Rebolo Rafael , Santos Nuno C , Sousa Sérgio G , Suárez Mascareño Alejandro
Published: September 2024

Chemical evolution models predict a gradual build-up of 13C in the Universe, based on empirical nuclear reaction rates and assumptions on the properties of stellar populations. However, old metal-poor stars within the Galaxy contain more 13C than is predicted, suggesting that further refinements to the models are necessary. Gas at high-redshift provides important supplementary information at metallicities $-2\lesssim \left[{\rm Fe/H}\right]\lesssim -1$, for which there are only a few measurements in the Galaxy. We obtained new, high-quality, VLT/ESPRESSO observations of the QSO B1331$+$170 and used them to measure 12C/13C in the damped Lyman-$\alpha$ system (DLA) at $z_{\rm abs}=1.776$, with $\left[{\rm Fe/H}\right]$ = −1.27. ai-vpfit, an artificial intelligence tool based on genetic algorithms and guided by a spectroscopic information criterion, was used to explore different possible kinematic structures of the carbon gas. Three hundred independent ai-vpfit models of the absorption system were produced using pre-set 12C/13C values, ranging from 4 to 500. Our results show that ${\rm ^{12}C / ^{13}C}=28.5^{+51.5}_{-10.4}$, suggesting a possibility of 13C production at low metallicity.
CRISPR screening uncovers nucleolar RPL22 as a heterochromatin destabilizer and senescence driver
Authors: Li Hong-Yu , Wang Min , Jiang Xiaoyu , Jing Yaobin , Wu Zeming , He Yifang , Yan Kaowen , Sun Shuhui , Ma Shuai , Ji Zhejun , Wang Si , Belmonte Juan Carlos Izpisua , Qu Jing , Zhang Weiqi , Wei Taotao , Liu Guang-Hui
Published: September 2024

Dysfunction of the ribosome manifests during cellular senescence and contributes to tissue aging, functional decline, and development of aging-related disorders in ways that have remained enigmatic. Here, we conducted a comprehensive CRISPR-based loss-of-function (LOF) screen of ribosome-associated genes (RAGs) in human mesenchymal progenitor cells (hMPCs). Through this approach, we identified ribosomal protein L22 (RPL22) as the foremost RAG whose deficiency mitigates the effects of cellular senescence. Consequently, absence of RPL22 delays hMPCs from becoming senescent, while an excess of RPL22 accelerates the senescence process. Mechanistically, we found in senescent hMPCs, RPL22 accumulates within the nucleolus. This accumulation triggers a cascade of events, including heterochromatin decompaction with concomitant degradation of key heterochromatin proteins, specifically heterochromatin protein 1γ (HP1γ) and heterochromatin protein KRAB-associated protein 1 (KAP1). Subsequently, RPL22-dependent breakdown of heterochromatin stimulates the transcription of ribosomal RNAs (rRNAs), triggering cellular senescence. In summary, our findings unveil a novel role for nucleolar RPL22 as a destabilizer of heterochromatin and a driver of cellular senescence, shedding new light on the intricate mechanisms underlying the aging process.
Nucleotide excision repair of aflatoxin-induced DNA damage within the 3D human genome organization
Authors: Wu Yiran , Adeel Muhammad Muzammal , Xia Dian , Sancar Aziz , Li Wentao
Published: September 2024

Aflatoxin B1 (AFB1), a potent mycotoxin, is one of the environmental risk factors that cause liver cancer. In the liver, the bioactivated AFB1 intercalates into the DNA double helix to form a bulky DNA adduct which will lead to mutation if left unrepaired. Here, we adapted the tXR-seq method to measure the nucleotide excision repair of AFB1-induced DNA adducts at single-nucleotide resolution on a genome-wide scale, and compared it with repair data obtained from conventional UV-damage XR-seq. Our results showed that transcription-coupled repair plays a major role in the damage removal process. We further analyzed the distribution of nucleotide excision repair sites for AFB1-induced DNA adducts within the 3D human genome organization. Our analysis revealed a heterogeneous AFB1–dG repair across four different organization levels, including chromosome territories, A/B compartments, TADs, and chromatin loops. We found that chromosomes positioned closer to the nuclear center and regions within A compartments have higher levels of nucleotide excision repair. Notably, we observed high repair activity around both TAD boundaries and loop anchors. These findings provide insights into the complex interplay between AFB1-induced DNA damage repair, transcription, and 3D genome organization, shedding light on the mechanisms underlying AFB1-induced mutagenesis.
Antibody-mediated rejection diagnosed in early protocol biopsies in high immunological risk kidney transplant recipients
Authors: Arana Carolt , Hermida Evelyn , Rovira Jordi , Caro José Luis , Cucchiari David , Larque Ana Belén , Palou Eduard , Torres Juan , Montagud-Marrahi Enrique , Cuadrado-Páyan Elena , Rodriguez Diana , Cacho Judit , Gonzalez Angela , Reinoso Johanna , Nicolau Carlos , Esforzado Nuria , Torregrosa Vicente , Piñeiro Gastón , Revuelta Ignacio , Cofan Federico , Diekmann Fritz , Ventura-Aguiar Pedro , Oppenheimer Federico
Published: September 2024

Background

Renal transplant recipients with donor-specific anti-HLA antibodies are at an increased risk of antibody-mediated rejection (ABMR). Early protocolized renal biopsies may serve as a strategy to improve diagnosis in this patient population.

Methods

We evaluated 155 highly sensitized renal transplant recipients with cPRA class I + II >90% pre-transplant from 2015 to 2022. Patients with protocol biopsies within the first 2 weeks post-transplant were included.

Results

A total of 122 patients were included in the study. Of these, 13 (10.6%) were diagnosed with very early antibody-mediated rejection (veABMR) within the first 2 weeks post-transplant. This corresponds to 52% (13/25 patients) of all ABMR cases reported during the follow-up of this population. The graft survival rates at 1 and 3 years were significantly lower in patients with veABMR (P < .001) compared with patients without rejection in the early protocol biopsy. In terms of severity, the veABMR cohort exhibited a hazard ratio (HR) of 10.33 (95% confidence interval 3.23–33.06, P < .001) for graft failure. The presence of donor-specific antibodies class II on the day of transplantation and a higher percentage of eplet mismatch (EpMM), particularly EpMM DQA1, correlated with the development of veABMR.

Conclusion

Early protocol biopsies play a pivotal role in the early detection of veABMR in high-risk immunological patients. Patients with veABMR face significant risks of graft loss, despite early treatment of rejection.
Nutrigenetics and Nutritional Strategies in Systemic Arterial Hypertension: Evidence From a Scoping Review
Authors: Holzbach Luciana C , Brandão-Lima Paula N , Duarte Graziela B S , Rogero Marcelo M , Cominetti Cristiane
Published: September 2024

Nutrition and genetics have individual roles in systemic arterial hypertension (SAH); however, they can interact, influencing the regulation of blood pressure (BP) levels. The aim of this study was to evaluate the available evidence regarding gene–nutrient interactions in modulating BP levels in adults with SAH. The review followed the recommendations of the Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Twelve studies met the inclusion criteria for this review, reporting on 20 genes and 31 single nucleotide polymorphisms (SNPs), with 19 of them associated with BP variations. The most frequently evaluated SNPs were ACE rs4646994 and AT1R rs5186. Among the nutritional interventions, dietary sodium content was the focus of most studies (n = 11). Interactions with sodium consumption were observed for the following SNPs: KDM1A rs587168, EDNRB rs5351, LSS rs2254524, IRS1 rs1801278, KCNK9 rs6997709, ACE rs4646994, GNB3 rs5443, PPARG rs4684847, EDN1 rs5370, BCAT1 rs7961152, IL18 rs5744292, NOS3 rs2070744, and AT1R rs5186. In the presence of a diet rich in fruits and vegetables, moderate alcohol consumption, and reduced sodium intake, the SNP AT2R rs11091046 was associated with a decrease in BP levels. Furthermore, the SNP MTHFR rs1801133 exhibited an interaction with riboflavin supplementation in affecting BP levels. The evidence regarding the interaction between genetics and diet on BP levels remains limited. Among the existing findings, an interaction was observed between sodium, calcium, riboflavin, and specific polymorphisms; however, the underlying mechanisms for these interactions have yet to be identified. Note: This paper is part of the Nutrition Reviews Special Collection on Precision Nutrition.
Plasma diagnostics of supernova remnant 3C 400.2 by Suzaku observations
Authors: Onuma Masataka , Nobukawa Kumiko K , Nobukawa Masayoshi , Yamauchi Shigeo , Uchiyama Hideki
Published: September 2024

We report on the results of plasma diagnostics of the supernova remnant (SNR) 3C 400.2, which has been reported to have a recombining plasma by previous studies. For careful background estimation, we simultaneously fitted spectra extracted from the SNR and background regions and evaluated the SNR emission contaminating the background-region spectrum as well as the background emission in the source-region spectrum. The SNR emission is explained by the collisional ionization equilibrium plasma originating from the interstellar medium and the ionizing plasma originating from the ejecta, in contrast to previous studies. In addition, we found an unidentified X-ray source near the SNR, Suzaku J1937.4$+$1718, which is accompanied by an emission line at $\sim$4.4 keV with a $2.8\sigma$ confidence level. Because there is no striking atomic line at the energy in the rest frame, Suzaku J1937.4$+$1718 could be an extragalactic object with a redshifted Fe line.
Plant phytochrome interactions decode light and temperature signals
Authors: Yi Chengwei , Gerken Uwe , Tang Kun , Philipp Michael , Zurbriggen Matias D , Köhler Jürgen , Möglich Andreas
Published: September 2024

Plant phytochromes perceive red and far-red light to elicit adaptations to the changing environment. Downstream physiological responses revolve around red-light-induced interactions with phytochrome-interacting factors (PIFs). Phytochromes double as thermoreceptors, owing to the pronounced temperature dependence of thermal reversion from the light-adapted Pfr to the dark-adapted Pr state. Here, we assess whether thermoreception may extend to the phytochrome:PIF interactions. While the association between Arabidopsis (Arabidopsis thaliana) PHYTOCHROME B (PhyB) and several PHYTOCHROME-INTERACTING FACTOR (PIF) variants moderately accelerates with temperature, the dissociation does more so, thus causing net destabilization of the phytochrome:PIF complex. Markedly different temperature profiles of PIF3 and PIF6 might underlie stratified temperature responses in plants. Accidentally, we identify a photoreception mechanism under strong continuous light, where the extent of phytochrome:PIF complexation decreases with red-light intensity rather than increases. Mathematical modeling rationalizes this attenuation mechanism and ties it to rapid red-light-driven Pr⇄Pfr interconversion and complex dissociation out of Pr. Varying phytochrome abundance, e.g. during diurnal and developmental cycles, and interaction dynamics, e.g. across different PIFs, modify the nature and extent of attenuation, thus permitting light-response profiles more malleable than possible for the phytochrome Pr⇄Pfr interconversion alone. Our data and analyses reveal a photoreception mechanism with implications for plant physiology, optogenetics, and biotechnological applications.
Heterozygous fasciated ear mutations improve yield traits in inbred and hybrid maize lines
Authors: Wang Jinbiao , Zheng Qi , Zhang Ruizhong , Huang Zhaoyu , Wu Qingyu , Liu Lei , Ning Qiang , Jackson David , Xu Fang
Published: September 2024

Heterozygous mutations in two genes encoding key regulators of development improve kernel row number in inbred and hybrid maize, revealing their potential for yield improvement.
Tradable Risk Factors for Institutional and Retail Investors
Authors: Johansson Andreas , Sabbatucci Riccardo , Tamoni Andrea
Published: September 2024

We construct tradable risk factors using combinations of large and liquid mutual funds (long leg) and ETFs (exchange-traded funds) (long and short legs), based on their holdings, for both retail and institutional investors. Exploiting a novel dataset, our tradable factors take into account ETF shorting costs. Assessing the performance of our tradable factors against standard “on-paper” factors, we uncover an implementation shortfall of 2–4 percent annually. Shorting fees and transaction costs contribute to 58 percent of the performance differential between tradable and “on-paper” factors, assigning a non-trivial role to the opportunity cost of not trading the exact “on-paper” portfolio.
Demographic characteristics and comorbidities of patients with narcolepsy: a propensity-matched cohort study
Authors: Lipford Melissa C , Ip Wui , Awasthi Samir , Moore J Layne , Tippmann-Peikert Maja , Asfahan Shahir , Kumar-M Praveen , Pal Singh Gajinder , Gudeman Jennifer
Published: September 2024

Study Objectives

Narcolepsy has a complex phenotype owing to differences in symptomatology, disease severity, and comorbidities. This is the first study to use aggregate electronic health record (EHR) data and natural language processing (NLP) algorithms to characterize the demographics and comorbidities of a large cohort of patients with narcolepsy.

Methods

First-time Mayo Clinic patients (2000–2020) who had ≥1 narcolepsy-specific ICD-9/10 code and ≥1 disease-supportive statement in the clinical notes (identified using an NLP algorithm) were identified. A control cohort was propensity matched for birth year, age at first institutional encounter, sex, race, ethnicity, number of diagnosis codes, and mortality. Common comorbidities were compared and ranked between cohorts.

Results

In the EHR database (N = 6 389 186 patients), 2057 patients with narcolepsy were identified (median age, 32 years; 59.6% female; 92.6% white; and 89.2% non-Hispanic) and propensity matched with a control cohort. Among the top 20 comorbidities occurring more frequently in the narcolepsy cohort compared with the control cohort (odds ratio [OR], 1.67–3.94; p < .001]) were sleep disorders (restless legs syndrome, obstructive sleep apnea, and insomnia), mood disorders (depression, dysthymia, and anxiety), and pain disorders (chronic pain syndrome, migraine, fibromyalgia, carpal tunnel syndrome, and myalgia). Other comorbidities significantly associated with narcolepsy (OR, 1.33–1.95) were irritable bowel syndrome (p < .001), asthma (p < .001), cervical spondylosis (p < .01), syncope (p < .01), and hypothyroidism (p < .05).

Conclusions

This propensity-matched cohort study demonstrates increased psychiatric, sleep, and pain disorders in patients living with narcolepsy and challenges beyond narcolepsy-specific symptoms in this population. Understanding common narcolepsy-associated comorbidities may assist in tailoring treatment modalities.
Decoded cardiopoietic cell secretome linkage to heart repair biosignature
Authors: Garmany Armin , Arrell D Kent , Yamada Satsuki , Jeon Ryounghoon , Behfar Atta , Park Sungjo , Terzic Andre
Published: September 2024

Cardiopoiesis-primed human stem cells exert sustained benefit in treating heart failure despite limited retention following myocardial delivery. To assess potential paracrine contribution, the secretome of cardiopoiesis conditioned versus naïve human mesenchymal stromal cells was decoded by directed proteomics augmented with machine learning and systems interrogation. Cardiopoiesis doubled cellular protein output generating a distinct secretome that segregated the conditioned state. Altering the expression of 1035 secreted proteins, cardiopoiesis reshaped the secretome across functional classes. The resolved differential cardiopoietic secretome was enriched in mesoderm development and cardiac progenitor signaling processes, yielding a cardiovasculogenic profile bolstered by upregulated cardiogenic proteins. In tandem, cardiopoiesis enhanced the secretion of immunomodulatory proteins associated with cytokine signaling, leukocyte migration, and chemotaxis. Network analysis integrated the differential secretome within an interactome of 1745 molecules featuring prioritized regenerative processes. Secretome contribution to the repair signature of cardiopoietic cell-treated infarcted hearts was assessed in a murine coronary ligation model. Intramyocardial delivery of cardiopoietic cells improved the performance of failing hearts, with undirected proteomics revealing 50 myocardial proteins responsive to cell therapy. Pathway analysis linked the secretome to cardiac proteome remodeling, pinpointing 17 cardiopoiesis-upregulated secretome proteins directly upstream of 44% of the cell therapy-responsive cardiac proteome. Knockout, in silico, of this 22-protein secretome-dependent myocardial ensemble eliminated indices of the repair signature. Accordingly, in vivo, cell therapy rendered the secretome-dependent myocardial proteome of an infarcted heart indiscernible from healthy counterparts. Thus, the secretagogue effect of cardiopoiesis transforms the human stem cell secretome, endows regenerative competency, and upregulates candidate paracrine effectors of cell therapy-mediated molecular restitution.
Vascular smooth muscle BK channels limit ouabain‐induced vasocontraction: Dual role of the Na/K‐ATPase as a hub for Src‐kinase and the Na/Ca‐exchanger
Authors: Orth Tobias , Pyanova Anastasia , Lux Simon , Kaiser Peter , Reinheimer Isabel , Nielsen Daniel Løgstrup , Khalid Josef Ali , Rognant Salomé , Jepps Thomas A. , Matchkov Vladimir V. , Schubert Rudolf
Published: September 2024

Large‐conductance, calcium‐activated potassium channels (BK channels) and the Na/K‐ATPase are expressed universally in vascular smooth muscle. The Na/K‐ATPase may act via changes in the intracellular Ca2+ concentration mediated by the Na/Ca exchanger (NCX) and via Src kinase. Both pathways are known to regulate BK channels. Whether BK channels functionally interact in vascular smooth muscle cells with the Na/K‐ATPase remains to be elucidated. Thus, this study addressed the hypothesis that BK channels limit ouabain‐induced vasocontraction. Rat mesenteric arteries were studied using isometric myography, FURA‐2 fluorimetry and proximity ligation assay. The BK channel blocker iberiotoxin potentiated methoxamine‐induced contractions. The cardiotonic steroid, ouabain (10−5 M), induced a contractile effect of IBTX at basal tension prior to methoxamine administration and enhanced the pro‐contractile effect of IBTX on methoxamine‐induced contractions. These facilitating effects of ouabain were prevented by the inhibition of either NCX or Src kinase. Furthermore, inhibition of NCX or Src kinase reduced the BK channel‐mediated negative feedback regulation of arterial contraction. The effects of NCX and Src kinase inhibition were independent of each other. Co‐localization of the Na/K‐ATPase and the BK channel was evident. Our data suggest that BK channels limit ouabain‐induced vasocontraction by a dual mechanism involving the NCX and Src kinase signaling. The data propose that the NCX and the Src kinase pathways, mediating the ouabain‐induced activation of the BK channel, act in an independent manner.
Non‐canonical RNA‐binding protein ANXA11 regulates microRNA resorting into small extracellular vesicles to mediate cisplatin resistance
Authors: Zhang Yifan , Huang Qiang , Shen Yujie , Ren Henglei , Wu Chunping , Zhou Liang
Published: September 2024

The sensitivity of laryngeal squamous cell carcinoma (LSCC) to chemotherapy shows large heterogeneity. The role of miRNA in small extracellular vesicles (sEV) in chemotherapy resistance is under investigation. However, the regulation and sorting mechanism of sEV miRNAs remains unclear. In this study, small RNA sequencing was used to explore miRNA expression profiles in sEV of LSCC after cisplatin stimulation; RNA pull‐down, mass spectrometry, and EMSA were used to clarify the binding of candidate RNA‐binding protein (RBP) and candidate miRNA. Immunostaining and microRNA fluorescence in situ hybridization were performed to identify how candidate RBP affects miRNA stability and nuclear/cytoplasmic distribution. In vivo experiments were performed to verify the biological functions and response to cisplatin of candidate RBP. We found that cisplatin stimulation induced increased expression of miR‐148a‐3p and sEV sorting. ANXA11 binds to miR‐148a‐3p in a sequence‐specific manner. ANXA11 inhibits tumor cell proliferation and drug resistance by binding to and retaining miR‐148a‐3p. Cisplatin stimulation reduced ANXA11 expression and promoted miR‐148a‐3p efflux through sEV pathways. ANXA11 overexpression reduced in vivo tumor proliferation and cisplatin‐resistance. Taken together, ANXA11 mediates cisplatin resistance through sEV miRNA resorting. Mechanically, ANXA11 binds to miR‐148a‐3p in a sequence‐specific manner to regulate its resorting and thus influences tumor proliferation and chemoresistance.
Navigating Spaces of Belonging: Undergraduate Nursing Students’ Experiences in Online Learning Environments
Authors: Montague Janet , Haghiri-Vijeh Roya , Tsui Joyce , Connell Michelle , Cosgrove Caitlin
Published: September 2024

AIM

The aim of the study was to explore undergraduate nursing students’ experiences of belonging while studying online during the COVID-19 pandemic.

BACKGROUND

The use of online learning platforms increased drastically during the pandemic. Limited research exists on nursing students’ experiences of belonging while studying online.

METHOD

An explanatory sequential mixed-methods design was used for this study. This article reports on phase two, the qualitative component, which employed interpretive description methodology to understand nursing students’ experiences.

RESULTS

Ten semistructured interviews were completed, and four themes were identified: factors contributing to students’ sense of belonging online, navigating the online learning environment, creating safe online spaces during times of uncertainty, and students’ vision of developing a sense of belonging online.

CONCLUSION

Fostering nursing students’ sense of belonging is critical to their retention, persistence, and overall academic success when learning online.
Engaging Interprofessional Health Students in a Prescription Produce Plan
Authors: Battle Kimberly , Falls Katherine H. , Waters Leland , Slattum Patricia W. , Parsons Pamela L. , Wendte Jered M. , Diallo Ana F.
Published: September 2024

Nursing students participated in an interprofessional student-led prescription produce program (PPP) serving low-income older adults attending a community-based wellness and care coordination program. Students engaged in an online training module covering nutrition education and health promotion, integral components of a PPP. Ninety-five percent of students self-rated themselves as somewhat confident/very confident to participate in the PPP after completing an online learning module. Further investigation is needed on integrating students from diverse health professions to address the multifaceted factors related to nutrition and other social determinants of health affecting the management of chronic diseases.
Diagnostic Accuracy of Lipase as Early Predictor of Postoperative Pancreatic Fistula: Results from the LIPADRAIN study
Authors: Doussot Béranger , Doussot Alexandre , Ayav Ahmet , Santucci Nicolas , Deguelte Sophie , Sow Amadou Khalilou , El Amrani Mehdi , Duvillard Laurence , Piessen Guillaume , Girard Edouard , Mabrut Jean-Yves , Garnier Jonathan , Ortega-Deballon Pablo , Fournel Isabelle , Facy Olivier
Published: September 2024

Objective:

To evaluate the diagnostic accuracy of drain fluid lipase as an early predictor of postoperative pancreatic fistula and establish the most appropriate day for their measure.

Background:

Clinically relevant postoperative pancreatic fistula remains a potentially life-threatening complication after pancreatic surgery. Early detection strategies remain key to reduce both the incidence and the burden of pancreatic fistula.

Methods:

The LIPAse DRAIN (LIPADRAIN) study is a multicenter, prospective diagnostic study conducted in 7 tertiary university hospitals. Drain fluid values to detect clinically relevant postoperative pancreatic fistula from postoperative day 1 to postoperative day 6 were evaluated using receiver operating characteristic curve analysis. A biomarker was considered to be relevant for clinical use if its area under the curve (AUC) was greater than 0.75.

Results:

Of the 625 patients included in the analysis, clinically relevant postoperative pancreatic fistula occurred in 203 (32%) patients. On postoperative days 3 and 4, drain fluid lipase was a reliable biomarker to detect clinically relevant postoperative pancreatic fistula (AUC: 0.761; 95% confidence interval [CI]: 0.761–0.799 and AUC: 0.784; 95% CI: 0.743–0.821, respectively). On postoperative day 3, with a threshold of 299 units/L, drain fluid lipase yielded a negative predictive value of 51%, sensitivity of 78%, and specificity of 63% for the detection of clinically relevant postoperative pancreatic fistula.

Conclusions:

In this multicenter prospective study, drain fluid lipase is a reliable biomarker at postoperative days 3 and 4 for the diagnosis of clinically relevant postoperative pancreatic fistula after pancreatic surgery and should be systematically measured on postoperative day 3.
Reliability of a Photo-Based Modified Foot Posture Index (MFPI) in Quantifying Severity of Foot Deformity in Children With Cerebral Palsy
Authors: Georgiadis Andrew G. , Davids Jon R. , Goodbody Christine M. , Howard Jason J. , Karamitopoulos Mara S. , Payares-Lizano Monica , Pierz Kristan A. , Rhodes Jason T. , Shore Benjamin J. , Shrader M. Wade , Tabaie Sean A. , Thompson Rachel Mednick , Torres-Izquierdo Beltran , Wimberly Robert Lane , Hosseinzadeh Pooya ,   Research in Neuromuscular Orthopaedics (RINO) Study Group
Published: September 2024

Introduction:

Children with cerebral palsy (CP) have high rates of foot deformity. Accurate assessment of foot morphology is crucial for therapeutic planning and outcome evaluation. This study aims to evaluate the reliability of a novel photo-based Modified Foot Posture Index (MFPI) in the evaluation of foot deformity in children with CP.

Methods:

Thirteen orthopaedic surgeons with neuromuscular clinical focus from 12 institutions evaluated standardized standing foot photographs of 20 children with CP, scoring foot morphology using the MFPI. Raters scored the standardized photographs based on five standard parameters. Two parameters assessed the hindfoot: curvature above and below the malleoli and calcaneal inversion/eversion. Three parameters assessed the midfoot and forefoot: talonavicular congruence, medial arch height, and forefoot abduction/adduction. Summary MFPI scores range from −10 to +10, where positive numbers connote planovalgus, whereas negative numbers connote a tendency toward cavovarus. Intra- and interrater reliability were calculated using a 2-way mixed model of the intraclass correlation coefficient (ICC) set to absolute agreement.

Results:

Feet spanned the spectrum of potential pathology assessable by the MFPI, including no deformity, mild, moderate, and severe planovalgus or cavovarus deformities. All scored variables showed high intrarater reliability with ICCs from 0.891 to 1. ICCs for interrater reliability ranged from 0.965 to 0.984. Hindfoot total score had an ICC of 0.979, with a 95% CI, 0.968-0.988 (P<0.001). The forefoot total score had an ICC of 0.984 (95% CI, 0.976-0.991, P<0.001). Mean total score by the MFPI was 3.67 with an ICC of 0.982 (95% CI, 0.972-0.990, P<0.001).

Conclusions:

The photo-based MFPI demonstrates high intra- and interrater reliability in assessing foot deformities in children with CP. Its noninvasive nature and ease of use make it a promising tool for both clinical and research settings. MFPI should be considered as part of standard outcomes scores in studies regarding the treatment of CP-associated foot deformities.

Level of Evidence:

Level V.
Central Venous Oxygen Saturation for Estimating Mixed Venous Oxygen Saturation and Cardiac Index in the ICU: A Systematic Review and Meta-Analysis
Authors: Motazedian Pouya , Beauregard Nickolas , Letourneau Isabelle , Olaye Ida , Syed Sarah , Lam Eric , Di Santo Pietro , Mathew Rebecca , Clark Edward G. , Sood Manish M. , Lalu Manoj M. , Hibbert Benjamin , Bugeja Ann
Published: September 2024

OBJECTIVES:

The objectives of our systematic review and meta-analyses were to determine the diagnostic accuracy of central venous oxygen saturation (Scvo
2) in estimating mixed venous oxygen saturation (Svo
2) and cardiac index in critically ill patients.

DATA SOURCES:

A systematic search using MEDLINE, Cochrane Central Register of Controlled Trials, and Embase was completed on May 6, 2024.

STUDY SELECTION:

Studies of patients in the ICU for whom Scvo
2 and at least one reference standard test was performed (thermodilution and/or Svo
2) were included.

DATA EXTRACTION:

Individual patient data were used to calculate the pooled intraclass correlation coefficient (ICC) for Svo
2 and Spearman correlation for cardiac index. The Quality Assessment of Diagnostic Accuracy Studies-2 and Grading Recommendations Assessment, Development, and Evaluation tools were used for the risk of bias and certainty of evidence assessments.

DATA SYNTHESIS:

Of 3427 studies, a total of 18 studies with 1971 patients were identified. We meta-analyzed 16 studies (1335 patients) that used Svo
2 as a reference and three studies (166 patients) that used thermodilution as reference. The ICC for reference Svo
2 was 0.83 (95% CI, 0.75–0.89) with a mean difference of 2.98% toward Scvo
2. The Spearman rank correlation for reference cardiac index is 0.47 (95% CI, 0.46–0.48; p < 0.0001).

CONCLUSIONS:

There is moderate reliability for Scvo
2 in predicting Svo
2 in critical care patients with variability based on sampling site and presence of sepsis. There is limited evidence on the independent use of Scvo
2 in predicting cardiac index.
Meta-analysis of Targeted Therapies in EGFR-mutated Non–Small Cell Lung Cancer
Authors: Qureshi Zaheer , Altaf Faryal , Jamil Abdur , Siddique Rimsha
Published: September 2024

Background:

Some of the non–small cell lung cancer (NSCLC) cases enhance somatic mutations of the epidermal growth factor receptor (EGFR) gene within the tyrosine kinase inhibitor (TKI) domain. In such cases, first-line treatments are EGFR-TKIs, including osimertinib, erlotinib, or gefitinib. Therefore, this meta-analysis aims to assess the safety and efficacy of first-line targeted therapies for EGFR-mutated advanced NSCLC patients, focusing on osimertinib, erlotinib, and gefitinib.

Methods:

A systematic electronic search was conducted on 3 electronic databases—Scopus, PubMed, and Web of Science—from inception to May 2024 to locate relevant trials reporting the safety and efficacy of osimertinib, erlotinib, or gefitinib in treating EGFR-mutated advanced NSCLC. No language or data restriction was applied to the search strategy. The assessed effects were objective response rate (ORR) and disease control rate (DCR). RoB 2 tool was utilized to determine the risk of bias while R programming language performed all the statistical synthesis.

Results:

Out of 15,275 search results, only 19 trials were eligible for this meta-analysis. All the 3 EGFR-TKIs depicted effectiveness and safety among NSCLC patients, but osimertinib improved the ORR by 72% (95% CI: 65%, 78%) as compared with erlotinib (69% [95% CI: 58%, 79%]) and gefitinib (64% [95% CI: 64%, 78%]). Overall, the 3 EGFR-TKIs were effective by improving ORR 68% (95% CI: 63%, 73%). Similarly, osimertinib demonstrated highly effective impacts in disease control among NSCLC patients by 94% (95% CI: 91%, 97%) compared with gefitinib (68% [95% CI: 41%, 89%]). Overall, the 2 EGFR-TKIs were effective in disease control among NSCLC patients (82% [95% CI: 67%, 93%]).

Conclusions:

The pooled analyses have shown that erlotinib, gefitinib, and osimertinib are safe and effective first-line treatment options for patients with EGFR-mutated advanced NSCLC. The meta-analysis outcomes have demonstrated that osimertinib, erlotinib, or gefitinib positively impact overall response rate and disease control.
Impact of Adherence to Beta-Blockers in Patients With All-Comers ST-Segment Elevation Myocardial Infarction and According to Left Ventricular Ejection Fraction at Discharge: Results From the Real-World Registry FAST-STEMI
Authors: Giannino Giuseppe , Giacobbe Federico , Annone Umberto , Ravetti Emanuele , Rollo Cesare , Nebiolo Marco , Troncone Mattia , Di Vita Umberto , Morena Arianna , Carmagnola Ludovica , Angelini Filippo , De Filippo Ovidio , Bruno Francesco , Pancotti Corrado , Gaido Luca , Fariselli Piero , D'Ascenzo Fabrizio , Giammaria Massimo , De Ferrari Gaetano Maria
Published: September 2024

Beta-blockers are a crucial part of post–myocardial infarction (MI) pharmacological therapy. Recent studies have raised questions about their efficacy in patients without reduced left ventricular ejection fraction (LVEF). This study aims to assess adherence to beta-blockers after discharge for ST-segment elevation myocardial infarction (STEMI) and the impact of adherence on outcomes based on LVEF at discharge. The retrospective registry FAST-STEMI evaluated real-world adherence to main cardiovascular drugs in patients with STEMI between 2012 and 2017 by comparing purchased tablets with expected ones at 1 year through pharmacy registries. Optimal adherence was defined as ≥80%. Primary outcomes included all-cause and cardiovascular death while secondary outcomes were MI, major/minor bleeding events, and ischemic stroke. The study included 4688 patients discharged on beta-blockers. The mean age was 64 ± 12.3 years, 76% were male, and the mean LVEF was 49.2 ± 8.8%. The mean adherence at 1 year was 87.1%. Optimal adherence was associated with lower all-cause (adjusted hazard ratio, 0.62, 95% confidence interval, 0.41–0.92, P: 0.02) and cardiovascular (adjusted hazards ratio, 0.55, 95% confidence interval, 0.26–0.98, P: 0.043) mortality. In patients with LVEF ≤40%, optimal adherence was linked to reduced all-cause and cardiovascular mortality, but this was not found in patients with either preserved or mildly reduced LVEF. Predictors of cardiovascular mortality included older age, chronic kidney disease, male gender, and atrial fibrillation. Optimal adherence to beta-blocker therapy in patients with all-comers STEMI reduced all-cause and cardiovascular mortality at 1 year; once stratified by LVEF, this effect was confirmed only in patients with reduced LVEF (<40%) at hospital discharge. Impact of adherence to beta-blockers in all-comers STEMI patients and according to LVEF at discharge: results from the real-world registry FAST-STEMI.
Differential distribution of NAT2 polymorphisms and NAT2 acetylator phenotypes among indigenous populations of the Brazilian Amazon
Authors: Perini Jamila A. , Basta Paulo C. , Cardoso Jessica V. , Elias Anna Beatriz R. , Suarez-Kurtz Guilherme
Published: September 2024

Objectives

We report, for the first time, the distribution of four no-function NAT2 single nucleotide polymorphisms and inferred NAT2 acetylator phenotypes in three indigenous groups (Munduruku, Paiter-Suruí, and Yanomami), living in reservation areas in the Brazilian Amazon.

Methods

Two hundred and seventy-six participants from three indigenous groups (92 for each group) were included and genotyped for four NAT2 polymorphisms (rs1801279, rs1801280, rs1799930, and rs1799931) by the TaqMan system. Minor Allele Frequency (MAF) was determined and NAT2 acetylator phenotypes were inferred.

Results

NAT2 rs1801279G>A was absent in all cohorts; rs1799930G>A was absent in Yanomami and rare (MAF 0.016) in Munduruku and Paiter-Suruí; MAF of rs1801280T>C ranged five-fold (0.092–0.433), and MAF of rs1799931G>A varied between 0.179 and 0.283, among the three groups. The distribution of NAT2 phenotypes differed significantly across cohorts; the prevalence of the slow acetylator phenotype ranged from 16.3% in Yanomami to 33.3% in Munduruku to 48.9% in Paiter-Suruí. This three-fold range of variation is of major clinical relevance because the NAT2 slow phenotype is associated with higher risk of hepatotoxicity with antituberculosis chemotherapy and high incidence rates of tuberculosis and burden of latent infection among Munduruku, Paiter-Surui, and Yanomami peoples. According to the frequency of the NAT2 slow acetylator phenotype, the estimated number of individuals needed to be genotyped to prevent one additional event of hepatotoxicity range from 31 (Munduruku) to 39 (Paiter-Surui) and to 67 (Yanomami).

Conclusion

The rs1801279 polymorphism was not found in any of the cohorts, while the MAF of the other polymorphisms showed significant variation between the cohorts. The difference in the prevalence of the NAT2 slow acetylator phenotype, which is linked to isoniazid-induced hepatotoxicity, was observed in the different study cohorts.
Artificial intelligence for geographic atrophy: pearls and pitfalls
Authors: Enzendorfer Marie Louise , Schmidt-Erfurth Ursula
Published: September 2024

Purpose of review

This review aims to address the recent advances of artificial intelligence (AI) in the context of clinical management of geographic atrophy (GA), a vision-impairing late-stage manifestation of age-related macular degeneration (AMD).

Recent findings

Recent literature shows substantial advancements in the development of AI systems to segment GA lesions on multimodal retinal images, including color fundus photography (CFP), fundus autofluorescence (FAF) and optical coherence tomography (OCT), providing innovative solutions to screening and early diagnosis. Especially, the high resolution and 3D-nature of OCT has provided an optimal source of data for the training and validation of novel algorithms. The use of AI to measure progression in the context of newly approved GA therapies, has shown that AI methods may soon be indispensable for patient management. To date, while many AI models have been reported on, their implementation in the real-world has only just started. The aim is to make the benefits of AI-based personalized treatment accessible and far-reaching.

The most recent advances (pearls) and challenges (pitfalls) associated with AI methods and their clinical implementation in the context of GA will be discussed.
Privacy preserving technology in ophthalmology
Authors: Yang Yahan , Chen Xinwei , Lin Haotian
Published: September 2024

Purpose of review

Patient privacy protection is a critical focus in medical practice. Advances over the past decade in big data have led to the digitization of medical records, making medical data increasingly accessible through frequent data sharing and online communication. Periocular features, iris, and fundus images all contain biometric characteristics of patients, making privacy protection in ophthalmology particularly important. Consequently, privacy-preserving technologies have emerged, and are reviewed in this study.

Recent findings

Recent findings indicate that general medical privacy-preserving technologies, such as federated learning and blockchain, have been gradually applied in ophthalmology. However, the exploration of privacy protection techniques of specific ophthalmic examinations, like digital mask, is still limited. Moreover, we have observed advancements in addressing ophthalmic ethical issues related to privacy protection in the era of big data, such as algorithm fairness and explainability.

Future privacy protection for ophthalmic patients still faces challenges and requires improved strategies. Progress in privacy protection technology for ophthalmology will continue to promote a better healthcare environment and patient experience, as well as more effective data sharing and scientific research.
Vision language models in ophthalmology
Authors: Lim Gilbert , Elangovan Kabilan , Jin Liyuan
Published: September 2024

Purpose of review

Vision Language Models are an emerging paradigm in artificial intelligence that offers the potential to natively analyze both image and textual data simultaneously, within a single model. The fusion of these two modalities is of particular relevance to ophthalmology, which has historically involved specialized imaging techniques such as angiography, optical coherence tomography, and fundus photography, while also interfacing with electronic health records that include free text descriptions. This review then surveys the fast-evolving field of Vision Language Models as they apply to current ophthalmologic research and practice.

Recent findings

Although models incorporating both image and text data have a long provenance in ophthalmology, effective multimodal Vision Language Models are a recent development exploiting advances in technologies such as transformer and autoencoder models.

Vision Language Models offer the potential to assist and streamline the existing clinical workflow in ophthalmology, whether previsit, during, or post-visit. There are, however, also important challenges to be overcome, particularly regarding patient privacy and explainability of model recommendations.
Maximum Diameter of Ileocecal Lymph Nodes Measured Using Abdominal Ultrasonography Allows for the Discrimination of Yersinia pseudotuberculosis Infection from Kawasaki Disease
Authors: Kato Atsushi , Miyata Ippei , Nakamura Yoshitaka , Tanaka Takaaki , Koguchi Yutaka , Oishi Tomohiro , Nakano Takashi , Ouchi Kazunobu
Published: September 2024

Background:

This study aimed to determine whether the maximum diameter of ileocecal lymph nodes measured using abdominal ultrasonography is useful for differentiating Yersinia pseudotuberculosis infection from Kawasaki disease in the acute phase. The optimal maximum diameter cutoff of the ileocecal lymph nodes was also explored to optimize differentiation between these 2 diseases.

Methods:

We included pediatric patients <15 years old who met the diagnostic criteria for Kawasaki disease. Stool culture testing, loop-mediated isothermal amplification of stool specimens, and serological diagnosis were performed to confirm the presence or absence of Y. pseudotuberculosis infection.

Results:

Of the 122 patients included in the analysis, 17 were confirmed to have Y. pseudotuberculosis infection and 105 were not. The age (in months), white blood cell count, C-reactive protein level, prediction score (risk score) for nonresponse to intravenous immunoglobulin, and number of intravenous immunoglobulin doses did not differ significantly between the Y. pseudotuberculosis-positive and -negative groups. The maximum diameter of ileocecal lymph nodes was 6.0 (5.5–9.5) mm in the Y. pseudotuberculosis-positive group and 3.0 (2.5–3.8) mm in the Y. pseudotuberculosis-negative group (numbers presented as median, interquartile range), with a significantly larger diameter in the Y. pseudotuberculosis-positive group (P < 0.01, Mann–Whitney U test), suggesting potency of ultrasonography.

Conclusion:

In patients meeting the diagnostic criteria for Kawasaki disease, the possibility of Y. pseudotuberculosis infection is significantly higher if the maximum ileocecal lymph node diameter ≥5.1 mm. Its sensitivity and specificity being 100%, and 89.5%, respectively.
Accelerated Severity of Illness Score Enhances Prediction of Complicated Acute Hematogenous Osteomyelitis in Children
Authors: Jahan Tahmina A. , Lapin Norman A. , O’Connell Michael T. , Jo Chanhee , Ma Yuhan , Tareen Naureen G. , Copley Lawson A.
Published: September 2024

Background:

Severity of illness determination for children with acute hematogenous osteomyelitis should be accomplished during the earliest stages of evaluation to guide treatment and establish prognosis. This study objectively defines an outcome of complicated osteomyelitis and explores an illness severity-based model with an improved ability to predict this outcome as soon and accurately as possible, comparing it to existing models.

Methods:

Children with Staphylococcus aureus acute hematogenous osteomyelitis (n = 438) were retrospectively studied to identify adverse events and predictors of severity. The outcome of complicated osteomyelitis was ultimately defined as the occurrence of any major or at least 3 minor adverse events, which occurred in 52 children. Twenty-four clinical and laboratory predictors were evaluated through univariate and stacked multivariable regression analyses of chronologically distinct groups of variables. Receiver operating characteristic curve analyses were conducted to compare models.

Results:

Accelerated Severity of Illness Score included: triage tachycardia [odds ratio: 10.2 (95% confidence interval: 3.48–32.3], triage tachypnea [6.0 (2.4–15.2)], C-reactive proteininitial ≥17.2 mg/dL [4.5 (1.8–11.8)], white blood cell count band percentageinitial >3.8% [4.6 (2.0–11.0)], hemoglobininitial ≤10.4 g/dL [6.0 (2.6–14.7)], methicillin-resistant S. aureus [3.0 (1.2–8.5)], septic arthritis [4.5 (1.8–12.3)] and platelet nadir [7.2 (2.7–20.4)]. The receiver operating characteristic curve of Accelerated Severity of Illness Score [area under the curve = 0.96 (0.941–0.980)] were superior to those of Modified Severity of Illness Score = 0.903 (0.859–0.947), Acute Score for Complications of Osteomyelitis Risk Evaluation = 0.878 (0.830–0.926) and Chronic Score for Complications of Osteomyelitis Risk Evaluation = 0.858 (0.811–0.904). Successive receiver operating characteristic curve analyses established an exponentially increasing risk of complicated osteomyelitis for children with mild (0/285 or 0%), moderate (4/63 or 6.3%), severe (15/50 or 30.0%) and hyper-severe (33/40 or 82.5%) acute hematogenous osteomyelitis (P<0.0001).

Conclusions:

This study improves upon previous severity of illness models by identifying early predictors of a rigorously defined outcome of complicated osteomyelitis.