bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetics Research in Evolutionary Biology: Perspectives on Timescales and Mechanisms
Authors: Yi Soojin V
Published: September 2024

Epigenetics research in evolutionary biology encompasses a variety of research areas, from regulation of gene expression to inheritance of environmentally mediated phenotypes. Such divergent research foci can occasionally render the umbrella term “epigenetics” ambiguous. Here I discuss several areas of contemporary epigenetics research in the context of evolutionary biology, aiming to provide balanced views across timescales and molecular mechanisms. The importance of epigenetics in development is now being assessed in many nonmodel species. These studies not only confirm the importance of epigenetic marks in developmental processes, but also highlight the significant diversity in epigenetic regulatory mechanisms across taxa. Further, these comparative epigenomic studies have begun to show promise toward enhancing our understanding of how regulatory programs evolve. A key property of epigenetic marks is that they can be inherited along mitotic cell lineages, and epigenetic differences that occur during early development can have lasting consequences on the organismal phenotypes. Thus, epigenetic marks may play roles in short-term (within an organism's lifetime or to the next generation) adaptation and phenotypic plasticity. However, the extent to which observed epigenetic variation occurs independently of genetic influences remains uncertain, due to the widespread impact of genetics on epigenetic variation and the limited availability of comprehensive (epi)genomic resources from most species. While epigenetic marks can be inherited independently of genetic sequences in some species, there is little evidence that such “transgenerational inheritance” is a general phenomenon. Rather, molecular mechanisms of epigenetic inheritance are highly variable between species.
Synthesis of 2′-formamidonucleoside phosphoramidites for suppressing the seed-based off-target effects of siRNAs
Authors: Nomura Kohei , An Seongjin , Kobayashi Yoshiaki , Kondo Jiro , Shi Ting , Murase Hirotaka , Nakamoto Kosuke , Kimura Yasuaki , Abe Naoko , Ui-Tei Kumiko , Abe Hiroshi
Published: September 2024

In this study, we report the synthesis of 2′-formamidonucleoside phosphoramidite derivatives and their incorporation into siRNA strands to reduce seed-based off-target effects of small interfering RNAs (siRNAs). Formamido derivatives of all four nucleosides (A, G, C and U) were synthesized in 5–11 steps from commercial compounds. Introducing these derivatives into double-stranded RNA slightly reduced its thermodynamic stability, but X-ray crystallography and CD spectrum analysis confirmed that the RNA maintained its natural A-form structure. Although the introduction of the 2′-formamidonucleoside derivative at the 2nd position in the guide strand of the siRNA led to a slight decrease in the on-target RNAi activity, the siRNAs with different sequences incorporating 2′-formamidonucleoside with four kinds of nucleobases into any position other than 2nd position in the seed region revealed a significant suppression of off-target activity while maintaining on-target RNAi activity. This indicates that 2′-formamidonucleosides represent a promising approach for mitigating off-target effects in siRNA therapeutics.
Global data monitoring systems and early identification for kidney diseases
Authors: Irish Georgina , Caskey Fergus J , Davids M Razeen , Tonelli Marcello , Yang Chih-Wei , Arruebo Silvia , Damster Sandrine , Donner Jo-Ann , Jha Vivekanand , Levin Adeera , Nangaku Masaomi , Saad Syed , Ye Feng , Okpechi Ikechi G , Bello Aminu K , Johnson David W
Published: September 2024

Background

Data monitoring and surveillance systems are the cornerstone for governance and regulation, planning, and policy development for chronic disease care. Our study aims to evaluate health systems capacity for data monitoring and surveillance for kidney care.

Methods

We leveraged data from the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA), an international survey of stakeholders (clinicians, policymakers and patient advocates) from 167 countries conducted between July and September 2022. ISN-GKHA contains data on availability and types of kidney registries, the spectrum of their coverage, as well as data on national policies for kidney disease identification.

Results

Overall, 167 countries responded to the survey, representing 97.4% of the global population. Information systems in forms of registries for dialysis care were available in 63% (n = 102/162) of countries, followed by kidney transplant registries (58%; n = 94/162), and registries for non-dialysis chronic kidney disease (19%; n = 31/162) and acute kidney injury (9%; n = 14/162). Participation in dialysis registries was mandatory in 57% (n = 58) of countries; however, in more than half of countries in Africa (58%; n = 7), Eastern and Central Europe (67%; n = 10), and South Asia (100%; n = 2), participation was voluntary. The least-reported performance measures in dialysis registries were hospitalization (36%; n = 37) and quality of life (24%; n = 24).

Conclusions

The variability of health information systems and early identification systems for kidney disease across countries and world regions warrants a global framework for prioritizing the development of these systems.
Worldwide organization and structures for kidney transplantation services
Authors: Viecelli Andrea K , Gately Ryan , Barday Zunaid , Shojai Soroush , Arruebo Silvia , Caskey Fergus J , Damster Sandrine , Donner Jo-Ann , Jha Vivekanand , Levin Adeera , Nangaku Masaomi , Saad Syed , Tonelli Marcello , Ye Feng , Okpechi Ikechi G , Bello Aminu K , Johnson David W
Published: September 2024

Background

Kidney transplantation (KT) is the preferred modality of kidney replacement therapy with better patient outcomes and quality of life compared with dialytic therapies. This study aims to evaluate the epidemiology, accessibility and availability of KT services in countries and regions around the world.

Methods

This study relied on data from an international survey of relevant stakeholders (clinicians, policymakers and patient advocates) from countries affiliated with the International Society of Nephrology that was conducted from July to September 2022. Survey questions related to the availability, access, donor type and cost of KT.

Results

In total, 167 countries responded to the survey. KT services were available in 70% of all countries, including 86% of high-income countries, but only 21% of low-income countries. In 80% of countries, access to KT was greater in adults than in children. The median global prevalence of KT was 279.0 [interquartile range (IQR) 58.0–492.0] per million people (pmp) and the median global incidence was 12.2 (IQR 3.0–27.8) pmp. Pre-emptive KT remained exclusive to high- and upper-middle-income countries, and living donor KT was the only available modality for KT in low-income countries. The median cost of the first year of KT was $26 903 USD and varied 1000-fold between the most and least expensive countries.

Conclusion

The availability, access and affordability of KT services, especially in low-income countries, remain limited. There is an exigent need to identify strategies to ensure equitable access to KT services for people with kidney failure worldwide, especially in the low-income countries.
Integration of zinc anode and cement: unlocking scalable energy storage
Authors: Liu Zhaolong , Feng Pan , Liu Ruidan , Yuan Long , Meng Xiangyu , Tao Guanghui , Chen Jian , Ran Qianping , Hong Jinxiang , Liu Jiaping , Miao Changwen
Published: September 2024

The significant volume of existing buildings and ongoing annual construction of infrastructure underscore the vast potential for integrating large-scale energy-storage solutions into these structures. Herein, we propose an innovative approach for developing structural and scalable energy-storage systems by integrating safe and cost-effective zinc-ion hybrid supercapacitors into cement mortar, which is the predominant material used for structural purposes. By performing air entrainment and leveraging the adverse reaction of the ZnSO4 electrolyte, we can engineer an aerated cement mortar with a multiscale pore structure that exhibits dual functionality: effective ion conductivity in the form of a cell separator and a robust load-bearing capacity that contributes to structural integrity. Consequently, a hybrid supercapacitor building block consisting of a tailored cement mortar, zinc metal anode and active carbon cathode demonstrates exceptional specific energy density (71.4 Wh kg−1 at 68.7 W kg−1), high areal energy density (2.0 Wh m−2 at 1.9 W m−2), favorable cycling stability (∼92% capacity retention after 1000 cycles) and exceptional safety (endurance in a 1-hour combustion test). By demonstrating the scalability of the structural energy-storage system coupled with solar energy generation, this new device exhibits great potential to revolutionize energy-storage systems.
Epidemiology of Campylobacter Species Infection in Kidney Transplant Recipients: A Retrospective Multicentric Case-Control Study in France
Authors: Bos Feline , Gueneau Romain , Crepin Thomas , Tinévez Claire , Taton Benjamin , Couzi Lionel , Moreau Karine , Schvartz Betoul , Perrin Peggy , Gatault Philippe , Scemla Anne , Chatelet-Pouliquen Valérie , Levi Charlène , Kamar Nassim , Lanternier Fanny , Lanotte Philippe , Neau Didier , Merville Pierre , Lehours Philippe , Puges Mathilde , Kaminski Hannah
Published: September 2024

Background

Campylobacteriosis in kidney transplant recipients (KTRs) is the most common identified bacterial cause of diarrhea. Risk factors in KTRs are unknown.

Methods

A 10-year multicentric, retrospective 1:1 case-control study was performed in France between 2010 and 2020. The main aim was to identify factors associated with Campylobacter-related infection in KTRs. The KTRs with a functional graft and campylobacteriosis (positive stool culture and/or blood culture and/or positive nucleic amplification test) and their controls matched on transplantation date within the same center were included.

Results

We identified 326 patients with campylobacteriosis. The estimated incidence rate of campylobacteriosis was 2.3/1000 patient-years. The infection occurred at a median of 2.4 years posttransplantation. The independent risk factors for campylobacteriosis were use of corticosteroids as maintenance regimen (75.8% vs 66%; P < .001), acute rejection (8.9% vs 4%; P = .048), low lymphocyte count (0.96 vs 1.4 giga/liter (G/L); P < .001), and low basal estimated glomerular filtration rate (eGFR) (44.2 vs 57.5 mL/minute/1.73 m2; P < .001). A fluoroquinolone was initiated in 64 (21.4%) patients, with 51.1% of antimicrobial resistance, whereas almost all strains were erythromycin sensitive.

Conclusions

Campylobacteriosis has a higher incidence in the 2 first years of transplantation. The factors independently associated with campylobacteriosis are corticosteroids as maintenance immunosuppressive regimen, low lymphocyte counts, low eGFR, and a history of acute rejection. Due to high antimicrobial resistance with fluoroquinolone, the first line of treatment should be azithromycin.
The MdIAA29-MdARF4 complex plays an important role in balancing plant height with salt and drought stress responses
Authors: Lei Yingying , Chen Cui , Chen Wenjun , Dai Hongyan
Published: September 2024

Breeding dwarf apple (Malus domestica) varieties is a recent trend in agriculture because such varieties are easy to maintain and have high yields; however, dwarf apple trees generally have poor stress tolerance. Balancing apple plant height and stress response has been an important breeding goal. In this study, aux/indole-3-acetic acid 29 gene in apple (MdIAA29) overexpression lines (#1, #2, and #3) had reduced plant height by 39%, 31%, and 35%, respectively, suitable for close planting applications. Surprisingly, the dwarf MdIAA29-overexpressing lines also showed increased plant tolerance to salt and drought stresses. Further analysis showed that MdIAA29 inhibited the regulation of auxin response factor 4 (ARF4) on Gretchen Hagen 3.9 (GH3.9) gene and 9-cis-epoxycarotenoid dioxygenase 3 (NCED3) gene in apple and changed the contents of auxin and abscisic acid in different tissues, thus achieving a balance between plant height and stress tolerance. In addition, we also found that MdIAA7 enhanced the inhibitory effect of MdIAA29 on MdARF4. In brief, the MdIAA29-MdARF4 complex significantly impacts the height of apple plants and their ability to respond to salt and drought stress.
Frontloaded Home Health Physical Therapy Reduces Hospital Readmissions Among Medicare Fee-for-Service Beneficiaries
Authors: McLaughlin Kevin H , Levy Joseph F , Reiff Jenni S , Burgdorf Julia , Reider Lisa
Published: September 2024

Objective

The purpose of this paper is to determine a claims-based definition of frontloaded home health physical therapy (HHPT) and examine the effect of frontloaded HHPT visits on all-cause 30-day hospital readmissions.

Methods

This study used a retrospective analysis of Medicare fee-for-service claims from older adults (≥65 years) in the National Health and Aging Trends Study (2011–2017) with ≥1 HHPT visit within 30 days of a hospitalization (n = 1344 hospitalizations; weighted n = 7,727,384). An exploratory analysis of home health claim distribution was conducted to determine definitions of frontloaded HHPT. Generalized linear models were then used to examine the relationship between hospital readmission and each definition of frontloading.

Results

Four definitions of frontloaded HHPT were identified: ≥2 HHPT visits in the first week after discharge; ≥3 visits in the first week; ≥4 visits in the first 2 weeks; and ≥ 5 visits in the first 2 weeks. The adjusted risk of readmission was lower for older adults receiving frontloaded HHPT in the first week: (risk ratio [RR] for ≥2 vs <2 visits = 0.57; 95% CI = 0.41–0.79; RR for ≥3 vs <3 visits = 0.39; 95% CI = 0.22–0.72). The reduction in risk of readmission was even greater for older adults receiving ≥4 versus <4 HHPT visits (RR = 0.32; 95% CI = 0.21–0.48) and ≥ 5 versus <5 HHPT visits (RR = 0.27; 95% CI = 0.14–0.50) within the first 2 weeks. The effect of HHPT frontloading was greater for patients hospitalized with surgical versus medical diagnoses and for patients with diagnoses targeted by the Hospital Readmissions Reduction Program.

Conclusion

Frontloaded HHPT reduces 30-day hospital readmissions among Medicare beneficiaries. Additional research is needed to determine the optimal number of visits and those most likely to benefit from frontloaded HHPT.

Impact

Frontloaded HHPT can be an effective approach for reducing 30-day hospital readmissions among Medicare beneficiaries.

Lay Summary

This study found that providing home health physical therapist visits early and often after hospital discharge decreases the risk that patients will be readmitted over the next 30 days.
Sumsets in the set of squares
Authors: Elsholtz Christian , Wurzinger Lena
Published: September 2024

We study sumsets $\mathcal{A}+\mathcal{B}$ in the set of squares $\mathcal{S}$ (and, more generally, in the set of kth powers $\mathcal{S}_k$, where $k\geq 2$ is an integer). It is known by a result of Gyarmati that $\mathcal{A}+\mathcal{B}\subset \mathcal{S}_k \cap [1,N]$ implies that $\min(|\mathcal{A}|,|\mathcal{B}|)=O_k(\log N)$. Here, we study how the upper bound on $|\mathcal{B}|$ decreases, when the size of $|\mathcal{A}|$ increases (or vice versa). In particular, if $|\mathcal{A}|\geq C k^{\frac{1}{m}} m (\log N)^{\frac{1}{m}}$, then $|\mathcal{B}|=O_k(m^2 \log N)$, for sufficiently large N, a positive integer m and an explicit constant C > 0. For example, with $m\sim \log \log N$ this gives: If $|\mathcal{A}|\geq C_k \log \log N$, then $|\mathcal{B}|=O_k(\log N (\log \log N)^2)$.
Real-world data on tolerability of COVID-19 vaccination in patients with rheumatoid arthritis based on patient-reported outcomes
Authors: Feuchtenberger Martin , Kovacs Magdolna Szilvia , Eder Anna , Nigg Axel , Almanzar Giovanni , Prelog Martina , Schäfer Arne
Published: September 2024

Objectives

To assess tolerability of COVID-19 vaccination in patients with RA and controls based on patient-reported outcomes (PROs).

Methods

In total, 266 study participants were included at 6 ± 1 weeks after their second vaccination (BioNTech/Pfizer (72.2%), AstraZeneca (18.8%) and Moderna (9.0%)). In a cross-sectional, observational study design, PRO data were recorded regarding both total and symptom-level tolerability.

Results

Overall tolerability was very high according to the patients’ self-assessment scores (1.71 for the first and 1.72 for the second vaccination, 6-point Likert scale [1 (very good) to 6 (very poor)]) and did not differ significantly between patients with RA (n = 204) and controls (n = 62). Self-rated overall tolerability regarding first vaccination was significantly better (P = 0.002) in patients receiving mRNA vaccines (n = 193, mean tolerability 1.59) as compared with vector-vaccinated patients (n = 73, mean tolerability 2.04). Homologous or heterologous vaccination regimens had no statistically significant effect on vaccine tolerability (P = 0.131). Reservations about the vaccination were rare (6.4% for the first and 6.0% for the second vaccination) but significantly associated with poorer overall tolerability (P < 0.001) and significantly reduced willingness to recommend vaccination to others (P < 0.001 for the first and P = 0.004 for the second vaccination).

Conclusion

Based on these real-world data, tolerability of COVID-19 vaccination was very good in both RA patients and controls. Reservations against COVID-19 vaccination were rare overall, but if present, associated with a significantly worse tolerability and a significantly lower degree of recommendation.
Machine Learning for Continuous-Time Finance
Authors: Duarte Victor , Duarte Diogo , Silva Dejanir H
Published: September 2024

We develop an algorithm for solving a large class of nonlinear high-dimensional continuous-time models in finance. We approximate value and policy functions using deep learning and show that a combination of automatic differentiation and Ito’s lemma allows for the computation of exact expectations, resulting in a negligible computational cost that is independent of the number of state variables. We illustrate the applicability of our method to problems in asset pricing, corporate finance, and portfolio choice and show that the ability to solve high-dimensional problems allows us to derive new economic insights.
Credit Cycles, Expectations, and Corporate Investment
Authors: Gulen Huseyin , Ion Mihai , Jens Candace E , Rossi Stefano
Published: September 2024

We provide a systematic empirical assessment of the Minsky hypothesis that business fluctuations stem from irrational swings in expectations. Using predictable firm-level forecast errors, we build an aggregate index of irrational expectations and use it to provide three sets of results. First, we show that our index predicts aggregate credit cycles. Next, we show that these predictable credit cycles drive cycles in firm-level debt issuance and investment and similar cycles between financially constrained and unconstrained firms, as Minsky predicts. Finally, we show more pronounced cycles in firm-level financing and investment for firms with ex ante more optimistic expectations. (JEL G31, G32, G40, E32, E44)
Horizon-Dependent Risk Aversion and the Timing and Pricing of Uncertainty
Authors: Andries Marianne , Eisenbach Thomas M , Schmalz Martin C
Published: September 2024

Inspired by experimental evidence, we amend the recursive utility model to let risk aversion decrease with the temporal horizon. Our pseudo-recursive preferences remain tractable and retain appealing features of the long-run risk framework, notably its success at explaining asset pricing moments. In addition, our model addresses two challenges to the standard model. Calibrating the agents’ preferences to explain the equity premium no longer implies an extreme preference for early resolutions of uncertainty. Horizon-dependent risk aversion helps resolve key puzzles in finance on the valuation of assets across maturities and captures the term structure of equity risk premiums and its dynamics.
Revisiting MSS v. Belgium and Greece and Interim Measures before the European Court of Human Rights
Authors: Isa Daniel Victoria Oluwatobi , Ní Ghráinne Brid
Published: September 2024

This article examines the 2011 European Court of Human Rights judgment in MSS v. Belgium and Greece, which held that transferring an asylum applicant from Belgium to Greece violated the European Convention on Human Rights. Despite receiving praise for reaffirming state obligations, this article challenges the verdict. It argues that in MSS, the Court of Human Rights missed a crucial opportunity, leaving the applicant exposed to nearly two and a half years of hardship in Greece, rendering his final triumph before the Court insignificant. The article reimagines the case, envisioning the Court granting an interim measure to halt the transfer. The proposed alternative conclusion, which prioritises the applicant’s best interests, could result in substantial political and policy implications. The purpose of this article is to highlight the importance of interim measures in protecting migrants’ rights and to encourage the Court to employ them more frequently.
The global evolution and impact of systems biology and artificial intelligence in stem cell research and therapeutics development: a scoping review
Authors: Silva-Sousa Thayna , Usuda Júlia Nakanishi , Al-Arawe Nada , Frias Francisca , Hinterseher Irene , Catar Rusan , Luecht Christian , Riesner Katarina , Hackel Alexander , Schimke Lena F , Dias Haroldo Dutra , Filgueiras Igor Salerno , Nakaya Helder I , Camara Niels Olsen Saraiva , Fischer Stefan , Riemekasten Gabriela , Ringdén Olle , Penack Olaf , Winkler Tobias , Duda Georg , Fonseca Dennyson Leandro M , Cabral-Marques Otávio , Moll Guido
Published: September 2024

Advanced bioinformatics analysis, such as systems biology (SysBio) and artificial intelligence (AI) approaches, including machine learning (ML) and deep learning (DL), is increasingly present in stem cell (SC) research. An approximate timeline on these developments and their global impact is still lacking. We conducted a scoping review on the contribution of SysBio and AI analysis to SC research and therapy development based on literature published in PubMed between 2000 and 2024. We identified an 8 to 10-fold increase in research output related to all 3 search terms between 2000 and 2021, with a 10-fold increase in AI-related production since 2010. Use of SysBio and AI still predominates in preclinical basic research with increasing use in clinically oriented translational medicine since 2010. SysBio- and AI-related research was found all over the globe, with SysBio output led by the (US, n = 1487), (UK, n = 1094), Germany (n = 355), The Netherlands (n = 339), Russia (n = 215), and France (n = 149), while for AI-related research the US (n = 853) and UK (n = 258) take a strong lead, followed by Switzerland (n = 69), The Netherlands (n = 37), and Germany (n = 19). The US and UK are most active in SCs publications related to AI/ML and AI/DL. The prominent use of SysBio in ESC research was recently overtaken by prominent use of AI in iPSC and MSC research. This study reveals the global evolution and growing intersection among AI, SysBio, and SC research over the past 2 decades, with substantial growth in all 3 fields and exponential increases in AI-related research in the past decade.
Awake Tracheal Intubation: An Update
Authors: Warwick Eleanor , Yoon Soo , Ahmad Imran
Published: September 2024

Awake tracheal intubation (ATI) remains the “gold standard” technique in securing a definitive airway in conscious, self-ventilating patients with predicted or known difficult airways and the procedure is associated with a low failure rate. Since its inception a variety of techniques to achieve ATI have emerged and there have been accompanying advancements in pharmaceuticals and technology to support the procedure. In recent years there has been a growing focus on the planning, training and human factors involved in performing the procedure. The practice of ATI, does however, remain low around 1% to 2% of all intubations despite an increase in those with head and neck pathology. ATI, therefore, presents a skill that is key for the safety of patients but may not be practised with regularity by many anesthetists. In this article we therefore aim to highlight relevant guidance, recent literature and provide an update on the practical methods fundamental for successful ATI. We also discuss the crucial aspects of a safe airway culture and how this can help to embed training and maintenance of skills.
Glycemic Control and Risk of Congenital Malformations in Women With Type 1 Diabetes
Authors: Thorius Ida Holte , Petersen Janne , Husemoen Lise Lotte N. , Alibegovic Amra C. , Gall Mari-Anne , Damm Peter , Mathiesen Elisabeth R.
Published: September 2024

OBJECTIVE:

To investigate the association between maternal glycemic control and the risk of congenital malformations in offspring of women with type 1 diabetes and to examine whether there is a hemoglobin A1C (Hb A1C) threshold value at which the risk for malformations increases significantly.

METHODS:

Analyses were performed on data from a multinational, observational cohort of 1,908 liveborn offspring of women with type 1 diabetes recruited in early pregnancy from 17 countries between 2013 and 2018. Offspring with malformations were identified according to European Surveillance of Congenital Anomalies version 1.4 and categorized as having one or more major malformations or minor malformations exclusively. The association between first-trimester Hb A1C levels and the risk of congenital malformations was investigated with splines in crude and adjusted logistic regression models.

RESULTS:

In total, 11.9% of the offspring (n=227) of women with type 1 diabetes had congenital malformations, including 2.1% (n=40) with at least one severe malformation. Women giving birth to offspring with malformations had a higher prevalence of psychiatric disorders (13.2% vs 7.2%, P<.01), thyroid disorders (33.0% vs 26.7%, P<.05), and folic acid supplementation (87.1% vs 77.7%, P<.01). The Hb A1C levels in the first trimester were similar (median 6.8% [interquartile range 6.3–7.6%] vs 6.7% [6.2–7.6%], P=.13) compared with women giving birth to offspring without malformations. The spline analysis illustrated a curvilinear association between Hb A1C levels and the risk of malformations with no clear threshold values. Higher first-trimester Hb A1C levels were associated with an increased risk of malformations (crude odds ratio [OR] 1.13, 95% CI, 1.01–1.27, adjusted odds ratio [aOR] 1.29, 95% CI, 1.10–1.51) and major malformations (crude OR 1.49, 95% CI, 1.23–1.81, aOR 1.57, 95% CI, 1.15–2.09).

CONCLUSION:

An increased risk for congenital malformations was curvilinearly associated with higher Hb A1C levels in early pregnancy among women with type 1 diabetes without any threshold values identified.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT01892319.
Validation of Sagittal age-adjusted Score in Predicting Proximal Junctional Kyphosis/Failure and Clinical Outcomes Following Adult Spinal Deformity Surgery
Authors: Park Se-Jun , Park Jin-Sung , Kang Dong-Ho , Jung Kyung-Hun , Kang Min-Wook , Jung Choong-Won , Kim Hyun-Jun , Lee Chong-Suh
Published: September 2024

Study Design.

Retrospective study

Objectives.

To validate the sagittal age-adjusted score (SAAS) in predicting proximal junctional kyphosis/failure (PJK/F) and good clinical outcomes following adult spinal deformity (ASD) surgery.

Summary of Background Data.

SAAS is a relatively new assessment system that incorporates age-adjusted sagittal parameters of pelvic incidence (PI) - lumbar lordosis (LL), pelvic tilt (PT), and T1 pelvic angle (TPA) to predict the PJK/F. External validation is required to verify its clinical usefulness.

Methods.

We included patients with ASD undergoing ≥5-level fusion including the sacrum or pelvis. SAAS was calculated based on the scores of the three components: PI-LL, PT, and TPA. PJK/F rates and clinical outcomes were compared among the correction categories (undercorrection, matched correction, and overcorrection) for the SAAS as well as for each of the three components. PJK/F rates were compared according to the correction groups of the sagittal components and total SAAS using the chi-square test. Receiver operating characteristic (ROC) analysis was performed to evaluate the predictive ability of overcorrection to develop PJK/F for the three sagittal parameters and SAAS. PROMs at final follow-up were compared among correction groups using ANOVA with Bonferroni post-hoc corrections.

Results.

A total 411 patients were included in the study (mean age: 69.3 y, mean body mass index: 25.9 kg/m2, total levels fused: 7.7 levels, and follow-up duration: 43.3 mo). Postoperative SAAS categories were as follow: undercorrection (13.4%), matched correction (30.2%), and overcorrection (56.4%). The PJK/F rates were significantly higher in the overcorrection group relative to PI-LL component (P=0.001) as well as SAAS (P=0.038) compared to undercorrection or matched correction groups. The clinical outcomes were best in patients who achieved matched correction relative to PI-LL component as well as SAAS compared to the other correction groups. However, the differentiating power of clinical outcomes across the correction categories was greater in the PI-LL component than in the SAAS.

Conclusion.

This study validated the efficacy of SAAS system to differentiate PJK/F development and good clinical outcomes. However, its differentiating power seems to be largely attributable to the function of the PI-LL component, as the PI-LL correction status better predicted PJK/F risk and clinical outcomes than SAAS.
Pathogenic Detection by Metagenomic next-generation Sequencing in Spinal Infections
Authors: Yin Chuqiang , Cong Yanan , Wang Huafeng , Wang Dechun , Yang Xizhong , Wang Xuesong , Wang Ting
Published: September 2024

Study Design.

Retrospective, observational study.

Objective.

To evaluate the ability and value of metagenomic next-generation sequencing (mNGS) in detecting pathogens from spinal infections.

Background.

The pathogenic diagnosis of primary spinal infection is challenging. The widespread application of mNGs in clinical practice makes it particularly useful in detecting rare, emerging, and atypical complex infectious diseases.

Methods.

From January 2019 to December 2023, a retrospective collection of 120 samples was obtained from patients suspected of spinal infections and undergoing treatment. Pairwise comparisons between traditional laboratory tests and mNGS were conducted for all cases.

Results.

Among the 120 cases, 95 were diagnosed as spinal infections, while 25 were classified as non-infectious. Microbiological evidence was found in 59 cases, while 36 cases were clinically diagnosed as spinal infection without definitive microbiological evidence. Rare microorganisms such as Aspergillus fumigatus, Taifanglania major, and Coxiella burnetii were detected by mNGS. The positive rate of mNGS was significantly higher at 88.42% compared to microbiological culture (43.16%), P<0.001. At the genus level, mNGS exhibited a consistency rate of 86.44% (51/59) with confirmed microorganisms. MNGS demonstrated very good agreement with clinically confirmed microorganisms at the genus level (kappa=0.833). The sensitivity, specificity, positive predictive value, and negative predictive value of mNGS were 86.44%, 92.00%, 96.23%, and 74.19%, respectively.

Conclusions.

The mNGS test exhibits rapidity, efficiency, and accuracy, rendering it of immense diagnostic and therapeutic value in the realm of spinal infection diseases.
How Do Functional Comorbidities Affect PROMIS-PF Scores Following Lumbar Fusion Surgery?
Authors: Mizels Joshua , Connelly Jake , Martin Brook , Karamian Brian , Spiker W. Ryan , Lawrence Brandon D. , Brodke Darrel S. , Spina Nicholas T.
Published: September 2024

Study Design.

A retrospective review.

Objective.

The purpose of this study is to trend PROMIS PF scores following lumbar fusion surgery and to investigate how the presence of functional comorbidities affects PROMIS PF scores. In addition, we compare trends in PROMIS PF scores to the Oswestry Disability Index (ODI) and PROMIS Pain Interference (PI) scores.

Summary of Background Data.

National Institute of Health’s (NIH) Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) domain has been validated in spine surgery. However, little is known about how PROMIS-PF scores are affected by functional comorbidities and how these scores change in patients recovering from lumbar fusion surgery over time. In this study, we hypothesize that functional comorbidities negatively affect recovery.

Materials and Methods.

We retrospectively identified 1893 patients who underwent thoracolumbar, lumbar, or lumbosacral fusion for degenerative conditions between January 2, 2014, and January 7, 2022. We summarized PF at three-month intervals for 2 years following surgery between those with and without functional comorbidity, defined as the presence of congestive heart failure (HF), chronic obstructive pulmonary disease (COPD), cerebrovascular disease (CVD), or paraplegia. Mixed effects multivariable regressions were used to model between group trends in PF through 2 years postoperatively controlling for age, gender, indication, and surgical invasiveness. The minimally clinically important difference (MCID) was defined as 5+ point improvement from baseline in PF.

Results.

The cohort includes 1224 (65%) patients without functional comorbidity and 669 (35%) with functional comorbidity. The mean age was 65.0, and the Charlson index was 1.0 in the cohort without functional comorbidity compared with 65.4 and 3.8 in the cohort with functional comorbidity (P=0.552 and <0.001, respectively). The groups were otherwise similar with respect to surgical invasiveness index, vertebral levels, and spine diagnosis (all P>0.05). At 24 months postoperatively, the functional comorbidity group had a 2.5-point lower absolute PF score and a 1.3-point less improvement from baseline (P=0.012 and 0.190, respectively). 19.3% of patients in the functional comorbidity group achieved the MCID compared with 80.9% in patients without functional comorbidity (P<0.001).

Conclusions.

Based on PROMIS PF scores, patients with functional comorbidities do not recover to the same extent and are less likely to achieve an MCID compared with patients without baseline functional comorbidities. PROMIS-PF can help benchmark patients along their recovery, and other metrics may be needed to better understand the recovery of patients with functional comorbidities.
Tranexamic Acid in Mohs Micrographic Surgery: A Systematic Review
Authors: Kumar Eenika A. , Morris Lisa M. , Michalski-McNeely Basia M.
Published: September 2024

BACKGROUND

Tranexamic acid (TXA) is an antifibrinolytic that has historically been used to treat menorrhagia and bleeding disorders. Exploration of its use in procedures has grown, and it has shown promise in its ability to achieve hemostasis with low risk to patients. Analysis of its use in Mohs micrographic surgery (MMS) is warranted due to its potential superiority to traditional methods of achieving hemostasis (direct pressure, electrocoagulation, and sutures).

OBJECTIVE

To perform a systematic review of studies which evaluate the efficacy and safety profile of topical application or subcutaneous injection of TXA and analyze as it applies to MMS.

MATERIALS AND METHODS

A comprehensive literature search was conducted using the PubMed database to identify relevant studies using the search terms: “tranexamic acid” OR “TXA.” The search was performed up to December 1, 2023.

RESULTS

Tranexamic acid has a strong safety profile, and its effectiveness in achieving hemostasis is well-demonstrated. Tranexamic acid has reduced risk of bleeding complications compared with traditional methods of achieving hemostasis.

CONCLUSION

An extensive review of the literature has yielded positive results, suggesting the potential of TXA in improving patient outcomes, reducing surgical time, decreasing intraoperative and postoperative bleeding, and increasing overall patient satisfaction.
ChatGPT-4 Surpasses Residents: A Study of Artificial Intelligence Competency in Plastic Surgery In-service Examinations and Its Advancements from ChatGPT-3.5
Authors: Hubany Shannon S. , Scala Fernanda D. , Hashemi Kiana , Kapoor Saumya , Fedorova Julia R. , Vaccaro Matthew J. , Ridout Rees P. , Hedman Casey C. , Kellogg Brian C. , Leto Barone Angelo A.
Published: September 2024

Background:

ChatGPT, launched in 2022 and updated to Generative Pre-trained Transformer 4 (GPT-4) in 2023, is a large language model trained on extensive data, including medical information. This study compares ChatGPT’s performance on Plastic Surgery In-Service Examinations with medical residents nationally as well as its earlier version, ChatGPT-3.5.

Methods:

This study reviewed 1500 questions from the Plastic Surgery In-service Examinations from 2018 to 2023. After excluding image-based, unscored, and inconclusive questions, 1292 were analyzed. The question stem and each multiple-choice answer was inputted verbatim into ChatGPT-4.

Results:

ChatGPT-4 correctly answered 961 (74.4%) of the included questions. Best performance by section was in core surgical principles (79.1% correct) and lowest in craniomaxillofacial (69.1%). ChatGPT-4 ranked between the 61st and 97th percentiles compared with all residents. Comparatively, ChatGPT-4 significantly outperformed ChatGPT-3.5 in 2018–2022 examinations (P < 0.001). Although ChatGPT-3.5 averaged 55.5% correctness, ChatGPT-4 averaged 74%, a mean difference of 18.54%. In 2021, ChatGPT-3.5 ranked in the 23rd percentile of all residents, whereas ChatGPT-4 ranked in the 97th percentile. ChatGPT-4 outperformed 80.7% of residents on average and scored above the 97th percentile among first-year residents. Its performance was comparable with sixth-year integrated residents, ranking in the 55.7th percentile, on average. These results show significant improvements in ChatGPT-4’s application of medical knowledge within six months of ChatGPT-3.5’s release.

Conclusion:

This study reveals ChatGPT-4’s rapid developments, advancing from a first-year medical resident’s level to surpassing independent residents and matching a sixth-year resident’s proficiency.
The mechanism and treatment strategies of GSDMD-mediated pyroptosis in myocardial infarction
Authors: Li Yujuan , Xiang Yaozu , Liang Jiayi , Chen Yang
Published: September 2024

Acute myocardial infarction (MI) is associated with high morbidity and mortality and poses a significant challenge to human health. Despite advances in medicine, effective treatment options for MI are still associated with adverse outcomes, such as heart failure. Consequently, identifying the pathogenesis of MI is a promising avenue for developing practical treatments. The inflammatory response plays a critical role in the pathogenesis of MI. Gasdermin D (GSDMD)-mediated pyroptosis regulates the inflammatory response, which is a pathogenic and potential therapeutic target for MI. Therefore, anti-pyroptosis treatment is emerging as a promising therapeutic approach for MI. Overall, this article reviews the mechanism and treatment strategies for GSDMD-mediated pyroptosis in MI, with the hope of providing insights into pathogenic interventions.
Spherical Aberration Changes in Patients With Early Presbyopia Wearing Aspheric Multifocal Soft Contact Lenses in South Korea
Authors: Jang Hyo-Seung , Lee Koon-Ja
Published: September 2024

Objectives:

The aim of this study was to evaluate the impact of wearing center-near (CN) and center-distance (CD) multifocal contact lenses (MFCLs) on spherical aberrations and visual acuity in patients with early presbyopia.

Methods:

Fifty participants with early presbyopia wore CN-MFCLs and CD-MFCLs for 1 week. The average corrected refractive power was −2.65±1.67 D. Spherical aberration was measured using an auto-refractor after 1 week of lens use.

Results:

No significant difference in overall visual acuity was observed when using either lens. Participants favored CD-MFCLs for distance vision and CN-MFCLs for near vision. This study highlighted variations in aberration and satisfaction based on age, refractive errors, and individual responses. Patients with positive spherical aberrations tended to benefit from CN-MFCLs, which improved both distance and near vision, although additional correction was required for clear distance vision. Patients with early presbyopia generally preferred CN-MFCLs when positive aberration was prevalent, whereas those with negative aberration reported greater satisfaction with distance vision when wearing CD-MFCLs.

Conclusions:

This study confirmed that wearing MFCLs leads to changes in spherical aberration and visual acuity in patients with early presbyopia, particularly when positive aberration prevails. Future research should investigate these effects across different stages of presbyopia.
Outcomes of Photorefractive Keratectomy After Corneal Graft: Brief Review
Authors: Khan Muhammad Saim , Gonzales Alexander L. , Kofi Mostafa , Alio Jorge L.
Published: September 2024

Purpose:

The purpose of this brief review is to analyze the outcomes of customized photorefractive keratectomy in the correction of refractive errors and irregular astigmatism after corneal graft surgery.

Methods:

Two reviewers (M.S.K. and J.L.A.) independently performed a literature search in the MEDLINE/PubMed database, Google Scholar, and ResearchGate from January 2001 to October 2023. To analyze the efficacy, safety, and predictability of the procedure, primary outcomes such as mean change in uncorrected distance visual acuity, corrected distance visual acuity, and root mean square value (RMS) of higher order aberrations were studied. The complications and adverse reactions were analyzed to predict the safety of this procedure.

Results:

We identified those studies where customized (topography guided/wavefront guided) photograph refractive keratectomy was performed in patients with postkeratoplasty. Significant change in uncorrected distance visual acuity, corrected distance visual acuity, RMS of higher order aberrations, refractive cylinder, and mean spherical equivalent were observed. Corneal haze was the most common complication documented; however, this was more commonly documented by authors who have not used Mitomycin C in their patients.

Conclusions:

We found out that customized photograph refractive keratectomy is a safe, effective, and predictable method of treatment for refractive error and irregular astigmatism after keratoplasty.
Increased Risk of Glaucoma in Fuchs Endothelial Corneal Dystrophy Is Independent of TCF4 Trinucleotide Repeat Expansion
Authors: Xing Chao , Schultis Sara , Bondar Vladyslav , Gong Xin , Whitson Jess T. , Mootha V. Vinod
Published: September 2024

Purpose:

The purpose of this study was to determine the prevalence of glaucoma and/or ocular hypertension (G/OHTN) in patients with Fuchs endothelial corneal dystrophy (FECD) and correlate with FECD severity and TCF4 cytosine-thymine-guanine18.1 (CTG18.1) trinucleotide repeat expansion genotype.

Methods:

We included 167 FECD probands and 110 controls from the University of Texas Southwestern Medical Center FECD Genetics Study to estimate the association between FECD and G/OHTN. Participants underwent slit-lamp microscopy for the assessment of Krachmer grade disease severity of FECD. The diagnosis of G/OHTN was ascertained using a patient-reported history of G/OHTN, previous glaucoma surgery and/or glaucoma laser procedure, and use of glaucoma drops. Genomic DNA from blood of participants was used to genotype the CTG18.1 repeat polymorphism by fragment analysis using short tandem repeat and triplet repeat primed polymerase chain reaction assays.

Results:

We observed a 19.2% prevalence of G/OHTN in the FECD probands compared with that of 7.3% in controls. The odds ratio of developing G/OHTN in FECD cases compared with controls was estimated to be 3.34 with a 95% confidence interval of 1.42–7.79 adjusting for age and sex. Among FECD cases, the likelihood of developing G/OHTN correlated positively with Krachmer grade (P = 0.043) and age (P = 0.026). There was no statistical difference of the proportions of patients developing G/OHTN between FECD cases with and without TCF4 CTG18.1 repeat expansion (16 out of 94 and 15 out of 72, respectively, P > 0.05).

Conclusions:

Patients with clinically significant FECD should be routinely monitored for the development of glaucoma regardless of their TCF4 repeat expansion genotype.
Characterization of Gaze Metrics and Visual Search Pattern Among Glaucoma Patients While Viewing Real-World Images
Authors: Nagarajan Sangeetha , Meethal Najiya Sundu K. , Pel Johan J.M. , Asokan Rashima , Negiloni Kalpa , George Ronnie
Published: September 2024

Précis:

We quantified and compared the gaze metrics during target-oriented visual search tasks between glaucoma and healthy controls. On the basis of a mathematical concept we showed that due to glaucoma, focal search becomes prominent over global search.

Purpose:

Visual search (VS) which is essential for target identification and navigation is significantly impacted by glaucoma. VS metrics can be influenced by differences in cultural exposure or coping strategies, leading to varying VS patterns. This study aimed to explore and label the pattern of VS based on gaze metrics quantified using eye-tracking technology.

Methods:

Twenty-seven glaucoma subjects and 30 healthy controls [median age 51 (14) and 54 (19) y, respectively] underwent a VS experiment during which they had to identify specific targets from real-world images. Eye movements were recorded using a remote eye-tracker and gaze metrics—fixation count (FC), fixation duration (FD), saccade amplitude (SA), and VS time (VST) were computed and compared between the study groups. A Z-score-based coefficient “K” was derived to label the search patterns as global (K≤-0.1: short FD with long SA), focal (K≥+0.1: long FD with short SA), or a combination (K between ±0.1)

Results:

Similar to other ethnicities, Indian glaucoma subjects also exhibited statistically significantly increased FC, FD, and VST (P=0.01). Healthy controls presented a comparable proportion of focal (47%) and global (42%) search patterns while glaucoma subjects exhibited predominantly focal (56%) than global search patterns (26%, P=0.008).

Conclusions:

This study suggests that glaucoma subjects perform more focal searches during active gaze scanning. This change in viewing behavior reflects underlying compensatory strategies adapted for coping with their visual impairments. These search patterns can be influenced by factors such as saliency which requires further investigation.