bluuebunny/crossref_metadata_2025 huggingface dataset:
The Environmental History of the Antarctic
Authors: Grevsmühl Sebastian
Published: January 2024

The environmental history of the polar regions, and in particular of Antarctica, is a rather recent area of inquiry that is in many ways still in its infancy. As a truly multidisciplinary research field, environmental history draws much inspiration from a large diversity of fields of historical and social research, including economic history, diplomatic history, cultural history, the history of explorations, and science and technology studies. Although overarching book-length studies on the environmental history of Antarctica are still rare, historical scholars have already conducted many in-depth case studies related mostly to three major interrelated research topics: Antarctic governance, natural resource exploitation, and tourism. These recent historical efforts, carried out mostly by a new generation of historians, have thus far allowed the proposal of several powerful counternarratives, challenging the frequent yet erroneous assertion that environmental protection and conservation were completely absent from Antarctic affairs before the 1970s. In so doing, environmental historians started offering a much more complex and nuanced account of what is frequently referred to as the “greening” of Antarctica, going well beyond “declensionist” narratives and conservation success stories that commonly pervade not only environmental histories but also public discourse. Indeed, all recent historical studies agree that there is nothing inevitable about the “greening” of Antarctica, nor are conservation and environmental protection its natural destiny. Science, politics, imperialism, capitalism, and imaginaries all have played their part in this important history, a history that remains still largely to be written.
Illiterate Addenbrooke’s Cognitive Examination-III in Three Indian Languages: An Adaptation and Validation Study
Authors: Bhattacharyya Bidisha , Paplikar Avanthi , Varghese Feba , Das Gautam , Shukla Vasundhara , Arshad Faheem , Gupta Aakansha , Mekala Shailaja , Mukherjee Adreesh , Mukherjee Ruchira , Venugopal Aparna , Tripathi Manjari , Ghosh Amitabha , Biswas Atanu , Alladi Suvarna
Published: January 2024

Background

Literacy is an important factor that predicts cognitive performance. Existing cognitive screening tools are validated only in educated populations and are not appropriate for older adults with little or no education leading to poor performance on these tests and eventually leading to misdiagnosis. This challenge for clinicians necessitates a screening tool suitable for illiterate or low-literate older individuals.

Objectives

The objective was to adapt and validate Addenbrooke’s Cognitive Examination-III (ACE-III) for screening general cognitive functions in illiterate and low-literate older populations in the Indian context in three languages.

Method

The Indian illiterate ACE-III was systematically adapted by modifying the original items of the Indian literate ACE-III to assess the cognitive functions of illiterates and low-literates with the consensus of an expert panel of professionals working in the area of dementia and related disorders. A total of 180 illiterate or low-literate participants (84 healthy-controls, 50 with dementia, and 46 with mild cognitive impairment [MCI]) were recruited from three different centers speaking Bengali, Hindi, and Kannada to validate the adapted version.

Results

The optimal cut-off score for illiterate ACE-III to distinguish controls from dementia in all 3 languages was 75. The optimal cut-off scores in distinguishing between controls and MCI ranged from 79 to 82, with a sensitivity ranging from 93% to 99% and a specificity ranging from 72% to 99%.

Conclusion

The test is found to have good psychometric properties and is a reliable cognitive screening tool for identifying dementia and MCI in older adults with low educational backgrounds in the Indian context.
Comparison of Plasma Concentration of Linezolid’s Detection by FICA and LC–MS/MS
Authors: Chen Jing , Zhu Chenxia , He Yangjin , Cao Hengbin
Published: January 2024

Linezolid was the first totally synthetic oxazolidinone antibiotic that was approved for clinical use against Mycobacterium tuberculosis. Our study investigated the correlation and consistency of fluorescence immunochromatography assay (FICA) and high-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) in measuring linezolid levels in the plasma. Plasma samples were collected from 80 to 100 tuberculosis patients. The samples were analyzed by FICA and LC–MS/MS, and linezolid levels measured by the two methods were compared by outlier test, correlation coefficient, Bland–Altman scatter plot, Deming regression analysis and bias evaluation. A total of 83 plasma samples were collected, all of which were non-outlier. The correlation coefficient of FICA and LC–MS/MS results was 0.9845. Deming regression analysis showed that the regression equation of FICA and LC–MS/MS was y = 0.2229 + 1.0076x. The medical decision levels of 2 and 7 μg/mL were taken into the regression equation, and the 95% CI of 2- and 7-μg/mL bias were both within the allowed error range. The findings indicated a strong correlation between the results obtained from FICA and LC–MS/MS were consistent showed good correlation, demonstrating their equivalence in measurement.
Efficient healthcare with large language models: optimizing clinical workflow and enhancing patient care
Authors: Tripathi Satvik , Sukumaran Rithvik , Cook Tessa S
Published: January 2024

Purpose

This article explores the potential of large language models (LLMs) to automate administrative tasks in healthcare, alleviating the burden on clinicians caused by electronic medical records.

Potential

LLMs offer opportunities in clinical documentation, prior authorization, patient education, and access to care. They can personalize patient scheduling, improve documentation accuracy, streamline insurance prior authorization, increase patient engagement, and address barriers to healthcare access.

Caution

However, integrating LLMs requires careful attention to security and privacy concerns, protecting patient data, and complying with regulations like the Health Insurance Portability and Accountability Act (HIPAA). It is crucial to acknowledge that LLMs should supplement, not replace, the human connection and care provided by healthcare professionals.

Conclusion

By prudently utilizing LLMs alongside human expertise, healthcare organizations can improve patient care and outcomes. Implementation should be approached with caution and consideration to ensure the safe and effective use of LLMs in the clinical setting.
Feasibility of cross-vendor linkage of ophthalmic images with electronic health record data: an analysis from the IRIS Registry®
Authors: Mbagwu Michael , Chu Zhongdi , Borkar Durga , Koshta Alex , Shah Nisarg , Torres Aracelis , Kalvaria Hylton , Lum Flora , Leng Theodore
Published: January 2024

Purpose

To link compliant, universal Digital Imaging and Communications in Medicine (DICOM) ophthalmic imaging data at the individual patient level with the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight).

Design

A retrospective study using de-identified EHR registry data.

Subjects, Participants, Controls

IRIS Registry records.

Materials and Methods

DICOM files of several imaging modalities were acquired from two large retina ophthalmology practices. Metadata tags were extracted and harmonized to facilitate linkage to the IRIS Registry using a proprietary, heuristic patient-matching algorithm, adhering to HITRUST guidelines. Linked patients and images were assessed by image type and clinical diagnosis. Reasons for failed linkage were assessed by examining patients' records.

Main Outcome Measures

Success rate of linking clinicoimaging and EHR data at the patient level.

Results

A total of 2 287 839 DICOM files from 54 896 unique patients were available. Of these, 1 937 864 images from 46 196 unique patients were successfully linked to existing patients in the registry. After removing records with abnormal patient names and invalid birthdates, the success linkage rate was 93.3% for images. 88.2% of all patients at the participating practices were linked to at least one image.

Conclusions and Relevance

Using identifiers from DICOM metadata, we created an automated pipeline to connect longitudinal real-world clinical data comprehensively and accurately to various imaging modalities from multiple manufacturers at the patient and visit levels. The process has produced an enriched and multimodal IRIS Registry, bridging the gap between basic research and clinical care by enabling future applications in artificial intelligence algorithmic development requiring large linked clinicoimaging datasets.
Anticipation in the biosciences and the human right to science
Authors: Boggio Andrea
Published: January 2024

Anticipation entails contemplating the beneficial and harmful impacts of scientific and technological progress. Anticipation has a long history in science, technology, and innovation policy partly due to future impacts of scientific progress being inescapable. The link between anticipation, an undertheorized concept, and human rights law is yet to be fully explored. This paper links anticipation to the rights to science, a lesser-studied human right codified in the International Covenant on Economic, Social, and Cultural Rights. The paper argues that the normative content of the right includes anticipation entitlements and duties. Combining the entitlements and duties with anticipation typologies leads to identifying three forms of anticipation that governments (and, in some cases, scientists) must carry out: beneficial, responsible, and participatory anticipation. The paper concludes by identifying three ways in which further conceptual work can enrich human-rights-based anticipation.
Offshore oil and gas infrastructure electrification and offshore wind: a legal exploration
Authors: Herrera Anchustegui Ignacio , Tscherning Rudiger
Published: January 2024

The oil and gas and renewable energy sectors are increasingly coming together as traditional hydrocarbon producers are exploring the large-scale integration of renewables in fossil-fuel projects. One option is the electrification of oil and gas production platforms in the offshore environment utilizing offshore wind energy to power the asset’s operations. This article assesses the rationale for such a shift as well as regulatory avenues and barriers to the electrification of offshore oil and gas assets through offshore wind energy technology. While the article’s explorations are of a general conceptual nature, this article studies existing and planned developments in Norway and Atlantic Canada.

This article discusses key factors to determine the legal nature of different electrification project models and proposes solutions to identify the likely legislative and regulatory regime(s) which will govern. The article concludes that reforms for a forward-thinking legal and regulatory environment for the offshore space will have to re-examine the role of existing (platform) and new (wind but also oil and gas) offshore infrastructure and the associated regime that applies to these projects. Currently, in the Norwegian and Canadian contexts, these discussions are somewhat exploratory. They do, however, underline the importance of planning the co-development of offshore wind energy projects with existing and future oil and gas projects and to highlight the need for greater clarity in the evolving design of legal and regulatory frameworks to support the future of the global offshore energy sector.
The most variable VVV sources: eruptive protostars, dipping giants in the nuclear disc and others
Authors: Lucas P W , Smith L C , Guo Z , Contreras Peña C , Minniti D , Miller N , Alonso-García J , Catelan M , Borissova J , Saito R K , Kurtev R , Navarro M G , Morris C , Muthu H , Froebrich D , Ivanov V D , Bayo A , Caratti o Garatti A , Sanders J L
Published: January 2024

We have performed a comprehensive search of a VISTA Variables in the Via Lactea (VVV) data base of 9.5 yr light curves for variable sources with ΔKs ≥ 4 mag, aiming to provide a large sample of high amplitude eruptive young stellar objects (YSOs) and detect unusual or new types of infrared variable source. We find 222 variable or transient sources in the Galactic bulge and disc, most of which are new discoveries. The sample mainly comprises novae, YSOs, microlensing events, Long Period Variable stars (LPVs), and a few rare or unclassified sources. Additionally, we report the discovery of a significant population of aperiodic late-type giant stars suffering deep extinction events, strongly clustered in the Nuclear Disc of the Milky Way. We suggest that these are metal-rich stars in which radiatively driven mass loss has been enhanced by super-solar metallicity. Among the YSOs, 32/40 appear to be undergoing episodic accretion. Long-lasting YSO eruptions have a typical rise time of ∼2 yr, somewhat slower than the 6–12 month time-scale seen in the few historical events observed on the rise. The outburst durations are usually at least 5 yr, somewhat longer than many lower amplitude VVV events detected previously. The light curves are diverse in nature, suggesting that multiple types of disc instability may occur. Eight long-duration extinction events are seen wherein the YSO dims for a year or more, attributable to inner disc structure. One binary YSO in NGC 6530 displays periodic extinction events (P=59 d) similar to KH 15D.
Mass estimates from optical modelling of the new TRAPUM redback PSR J1910−5320
Authors: Dodge O G , Breton R P , Clark C J , Burgay M , Strader J , Au K -Y , Barr E D , Buchner S , Dhillon V S , Ferrara E C , Freire P C C , Griessmeier J -M , Kennedy M R , Kramer M , Li K -L , Padmanabh P V , Phosrisom A , Stappers B W , Swihart S J , Thongmeearkom T
Published: January 2024

Spider pulsars continue to provide promising candidates for neutron star mass measurements. Here we present the discovery of PSR J1910−5320, a new millisecond pulsar discovered in a MeerKAT observation of an unidentified Fermi-LAT gamma-ray source. This pulsar is coincident with a recently identified candidate redback binary, independently discovered through its periodic optical flux and radial velocity. New multicolour optical light curves obtained with ULTRACAM/New Technology Telescope in combination with MeerKAT timing and updated SOAR/Goodman spectroscopic radial velocity measurements allow a mass constraint for PSR J1910−5320. icarus optical light curve modelling, with streamlined radial velocity fitting, constrains the orbital inclination and companion velocity, unlocking the binary mass function given the precise radio ephemeris. Our modelling aims to unite the photometric and spectroscopic measurements available by fitting each simultaneously to the same underlying physical model, ensuring self-consistency. This targets centre-of-light radial velocity corrections necessitated by the irradiation endemic to spider systems. Depending on the gravity darkening prescription used, we find a moderate neutron star mass of either 1.6 ± 0.2 or 1.4 ± 0.2 M⊙. The companion mass of either 0.45 ± 0.04 or $0.43^{+0.04}_{-0.03}$M⊙ also further confirms PSR J1910−5320 as an irradiated redback spider pulsar.
Studies on the soft intermediate state X-ray flare of MAXI J1535−571 during its 2017 outburst
Authors: Ma Ruican , Tao Lian , Méndez Mariano , Zhang Shuang-Nan , Xu Yanjun , Zhang Liang , Liu Hexin , Qu Jinlu , Song Liming , Ren Xiaoqin , Zhao Shujie , Huang Yue , Ma Xiang , Zhao Qingchang , Xu Yingchen , Li Panping , Yang Zixu , Yu Wei
Published: January 2024

We analysed an observation with the Nuclear Spectroscopic Telescope Array of the black hole X-ray binary MAXI J1535−571 in the soft intermediate state, in which we detected a 2.5-ks long flare. Our spectral fitting results suggest that MAXI J1535−571 possesses a high spin of $0.97_{-0.10}^{+0.02}$ and a low inclination of approximately 24°. We observed a gradual increase in the inner disc radius, as determined from fits to the continuum spectrum. This trend is inconsistent with an increased flux ratio of the thermal component, as well as the source evolving towards the soft state. This inconsistency may be attributed to a gradual decrease of the colour correction factor. Additionally, with a flare velocity of approximately 0.5 c and a higher hardness ratio during the flare period, the quasi-simultaneous detection of a type-B QPO in the Neutron Star Interior Composition Explorer data, and quasi-simultaneous ejecta launch through radio observations collectively provide strong evidence supporting the possibility that the flare originated from a discrete jet ejection.
Facile synthesis of nanoparticles-stacked Co3O4 nanoflakes with catalase-like activity for accelerating wound healing
Authors: Huang Yanan , Liao Wanyi , Wang Wenxuan , Zhang Tingting , Zhang Yan , Lu Lei
Published: January 2024

Delayed wound healing caused by excessive reactive oxygen species (ROS) remains a considerable challenge. In recent years, metal oxide nanozymes have gained significant attention in biomedical research. However, a comprehensive investigation of Co3O4-based nanozymes for enhancing wound healing and tissue regeneration is lacking. This study focuses on developing a facile synthesis method to produce high-stability and cost-effective Co3O4 nanoflakes (NFs) with promising catalase (CAT)-like activity to regulate the oxidative microenvironment and accelerate wound healing. The closely arranged Co3O4 nanoparticles (NPs) within the NFs structure result in a significantly larger surface area, thereby amplifying the enzymatic activity compared to commercially available Co3O4 NPs. Under physiological conditions, it was observed that Co3O4 NFs efficiently break down hydrogen peroxide (H2O2) without generating harmful radicals (·OH). Moreover, they exhibit excellent compatibility with various cells involved in wound healing, promoting fibroblast growth and protecting cells from oxidative stress. In a rat model, Co3O4 NFs facilitate both the hemostatic and proliferative phases of wound healing, consequently accelerating the process. Overall, the promising results of Co3O4 NFs highlight their potential in promoting wound healing and tissue regeneration.
A comparative study of boost dose delivery techniques in breast cancer radiotherapy optimising efficacy and minimising toxicity
Authors: El Ouardy Khalid , Zerfaoui Mustapha , Oulhouq Yassine , Bahhous Karim , Rrhioua Abdeslem , Bakari Dikra
Published: January 2024

The present study aims to compare three techniques for delivering a boost absorbed dose: conventional reduced tangential (3D), volumetric modulated arc therapy (VMAT) and fields forward-planned technique boost (3DF). The study included 15 postoperative breast cancer patients who received a boost absorbed dose following breast-conserving surgery. The conformity index and homogeneity index were used to evaluate treatment outcomes, along with the average absorbed dose received by organs at risk (OAR). All the calculated dosimetric plans are carried out using Monaco Treatment Planning System (TPS). VMAT offers superior conformity, dose homogeneity and target coverage, it is associated with higher absorbed doses to OAR such as the heart and lung. In contrast, the 3D and 3DF techniques exhibit advantages in reducing absorbed doses to critical structures, potentially minimising the risk of cardiac and pulmonary complications. Each technique has its advantages and disadvantages. The choice of technique should be individualised, taking into account patient-specific factors and treatment goals and involves a multidisciplinary approach.
Morphine compromises androgen biosynthesis by immature Leydig cells from pubertal rat testes in vitro
Authors: Lv Yao , Dong Yaoyao , Su Ming , Lin Hang , Zhu Qiqi , Li Huitao
Published: January 2024

Morphine is an analgesic in the opiate family, isolated from many plants. It can inhibit androgen biosynthesis by Leydig cells. Whether morphine directly inhibits androgen biosynthesis and underlying mechanism remains unclear. To investigate the influence of morphine on androgen secretion by rat immature Leydig cells (ILCs) and possible mechanism. Rat ILCs were treated with 0.5–50 μM morphine for 3 h in vitro. Morphine at ≥0.5 μM significantly reduced total androgen secretion. Morphine at 50 μM also compromised luteinizing hormone (LH, 10 mg/kg), 8Br-cAMP (1 mM), and 22R-hydroxycholesterol (20 μM) stimulated total androgen, androstanediol, and testosterone secretion, without affecting pregnenolone, progesterone, androstenedione mediated androgen secretion and testosterone and dihydrotestosterone mediated androstanediol secretion. Further analysis revealed that morphine at ≥0.5 μM downregulated Star expression and at ≥5 μM downregulated Cyp11a1 expression. Morphine also significantly reduced STAR (≥0.5 μM) and reduced CYP11A1 (≥5 μM) levels. 0.5 μM naloxone significantly antagonized morphine-mediated action. In conclusion, morphine might cause side effects by suppressing androgen biosynthesis via u opioid receptor.
Glycyrrhizin alleviates radiation-induced lung injury by regulating the NLRP3 inflammasome through endoplasmic reticulum stress
Authors: Chai Yuqing , Wang Ziming , Li Yun , Wang Yi , Wan Yu , Chen Xue , Xu Yang , Ge Lei , Li Hongxia
Published: January 2024

Objective

Radiation pneumonitis (RP) is the major adverse response of radiation therapy for thoracic malignant tumors, and there is a lack of effective interventions. The aim of this study was to investigate the radioprotective effect of Glycyrrhizin (GL) on RP and its potential mechanism.

Method

The body weight and lung weight of mice were monitored. HE staining was used to observe lung injury, and the expression of endoplasmic reticulum (ER) stress biomarkers and the activation of NLRP3 inflammasome were determined by Western blotting and immunohistochemistry. Flow cytometry was performed to check MLE-12 apoptosis. ER stress activator, Tunicamycin (Tuni), was used to verify the potential mechanism of GL. A systemic pharmacology explored the potential targets and pathways of GL.

Results

In this study, the lungs of irradiated mice showed significant pneumonic changes. In vivo and in vitro assay, NLRP3 inflammasome was significantly activated, the expression of ER stress biomarkers was elevated, flow cytometry confirms increased apoptosis in irradiated MLE-12 cells. GL inhibits the activation of NLRP3 inflammasome and ER stress pathways. Furthermore, systemic pharmacology revealed that the radioprotective effect of GL may be related to the MAPK signaling pathway.

Conclusion

In the present study, the results indicated that GL may regulate NLRP3 inflammasome through ER stress, thus exerting irradiation-protective effects on RP, and the ER stress pathway may be a potential target for RP treatment.
Virulence Patterns of Oat Crown Rust in Australia – Season 2022
Authors: Henningsen Eva C. , Lewis David , Nguyen Duong T. , Sperschneider Jana , Kianian Shahryar F. , Stone Eric , Dodds Peter N. , Figueroa Melania
Published: January 2024

Puccinia coronata f. sp. avenae (Pca) is an important foliar pathogen of oat which causes crown rust disease. The virulence profile of 48 Pca isolates derived from different locations in Australia was characterized using a collection of oat lines often utilized in rust surveys in the United States and Australia. This analysis indicates that Pca populations in Eastern Australia are broadly virulent, which contrasts with the population in Western Australia (WA). Several oat lines/Pc genes are effective against all rust samples collected from WA, suggesting they may provide useful resistance in this region if deployed in combination. We identified 19 lines from the United States oat differential set that display disease resistance to Pca in WA, with some in agreement with previous rust survey reports. We adopted the 10-letter nomenclature system to define oat crown rust races in Australia and compare the frequency of those virulence traits to published data from the United States. Based on this nomenclature, 42 unique races were detected among the 48 isolates, reflecting the high diversity of virulence phenotypes for Pca in Australia. Nevertheless, the Pca population in the United States is substantially more broadly virulent than that of Australia. Close examination of resistance profiles for the oat differential set lines after infection with Pca supports hypotheses of allelism or redundancy among Pc genes or the presence of several resistance genes in some oat differential lines. These findings illustrate the need to deconvolute the oat differential set using molecular tools.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Anaerobic Soil Disinfestation and Vermicompost to Manage Bottom Rot in Organic Lettuce
Authors: Neher Deborah A. , Brown Anna R. , Andrews Tucker D. , Weicht Thomas R.
Published: January 2024

Rhizoctonia solani Kühn (teleomorph: Thanatephorus cucumeris [Frank] Donk) is an aggressive soilborne pathogen with a wide host range that survives saprophytically between crops, presenting a challenge for organic vegetable farmers who lack effective management tools. A 2-year field experiment was conducted at two organic farms to compare anaerobic soil disinfestation (ASD) and worm-cured compost (vermicompost) to manage bottom rot caused by R. solani subspecies AG1-IB in field-grown organic lettuce (Lactuca sativa). At each farm, four replicate plots of seven treatments were arranged in a randomized complete block design. Randomization was restricted by grouping treatments to evaluate ASD, and treatments to evaluate vermicompost in starter plugs. ASD experiment treatments were three different ASD carbon sources that are commonly used and widely available to local farmers in Vermont: compost, cover crop residues, and poultry manure fertilizer, as well as a tarped control. Vermicompost experimental treatments were vermicompost compared with two types of controls: a commercial biocontrol product (RootShield PLUS + G), and unamended (untarped control). This study demonstrated that the ASD method is achievable in a field setting on Vermont farms. However, neither ASD nor vermicompost produced significant disease suppression or resulted in higher marketable yields than standard growing practices. Given the laborious nature of ASD, it is likely more appropriate in a greenhouse setting with high-value crops that could especially benefit from being grown in plastic tarped beds (e.g., tomatoes and strawberries). This study is the first known attempt of field-implemented ASD for soil pathogen control in the northeastern United States.
Whole-Body Vibration in Oncology Rehabilitation: Perceived Benefits, Barriers, and Clinician Willingness
Authors: Reader Ben , Bernstein Jennifer , Mersich Kaitlyn , Strenk Mariann L. , Benedict Jason , Greve Kelly
Published: January 2024

Background:

Patients with active and prior cancer diagnoses suffer a sequela of physical effects that negatively impact quality of life. Improvements in commonly impacted physiological systems have been achieved with the use of whole-body vibration (WBV). Current usage, appropriate diagnoses, and clinician perceptions of WBV remain unknown despite an increasing body of literature. The purpose of this study was to examine current practices and understand perceived indications, benefits, and barriers for the use of WBV in patients with cancer, particularly of clinicians working with pediatric populations.

Methods:

A Web-based survey was distributed via e-mail and social media posts to clinicians across the United States serving patients with cancer diagnoses.

Results:

Of a total of 72 responses, less than 3% of clinicians are currently using WBV in clinical practice. Diagnoses perceived as most appropriate for the use of WBV included leukemia/lymphoma (63.6%), central nervous system cancers (49.4%), and neuroblastoma (46.8%). Bone cancers were reported as the most inappropriate diagnoses (49.4%). Perceived benefits of WBV include improvements in blood flow, muscular strength, and bone mineral density. Lack of training (82%) and access to equipment (75%) were the most commonly reported barriers to use.

Conclusion:

WBV is perceived to be useful, safe, and beneficial for targeting effects of antineoplastic treatment for patients with cancer diagnoses, though current use is limited because of barriers of cost, access, and clinician knowledge.
Regulation of fatty acid synthase on tumor and progress in the development of related therapies
Authors: Bai Rilan , Cui Jiuwei
Published: January 2024

Fatty acid synthase (FASN) is an essential molecule in lipid metabolic pathways, which are crucial for cancer-related studies. Recent studies have focused on a comprehensive understanding of the novel and important regulatory effects of FASN on malignant biological behavior and immune-cell infiltration, which are closely related to tumor occurrence and development, immune escape, and immune response. FASN-targeting antitumor treatment strategies are being developed. Therefore, in this review, we focused on the effects of FASN on tumor and immune-cell infiltration and reviewed the progress of related anti-tumor therapy development.
Disulfiram: A novel repurposed drug for cancer therapy
Authors: Zeng Min , Wu Baibei , Wei Wenjie , Jiang Zihan , Li Peiqiang , Quan Yuanting , Hu Xiaobo
Published: January 2024

Cancer is a major global health issue. Effective therapeutic strategies can prolong patients' survival and reduce the costs of treatment. Drug repurposing, which identifies new therapeutic uses for approved drugs, is a promising approach with the advantages of reducing research costs, shortening development time, and increasing efficiency and safety. Disulfiram (DSF), a Food and Drug Administration (FDA)-approved drug used to treat chronic alcoholism, has a great potential as an anticancer drug by targeting diverse human malignancies. Several studies show the antitumor effects of DSF, particularly the combination of DSF and copper (DSF/Cu), on a wide range of cancers such as glioblastoma (GBM), breast cancer, liver cancer, pancreatic cancer, and melanoma. In this review, we summarize the antitumor mechanisms of DSF/Cu, including induction of intracellular reactive oxygen species (ROS) and various cell death signaling pathways, and inhibition of proteasome activity, as well as inhibition of nuclear factor-kappa B (NF-κB) signaling. Furthermore, we highlight the ability of DSF/Cu to target cancer stem cells (CSCs), which provides a new approach to prevent tumor recurrence and metastasis. Strikingly, DSF/Cu inhibits several molecular targets associated with drug resistance, and therefore it is becoming a novel option to increase the sensitivity of chemo-resistant and radio-resistant patients. Studies of DSF/Cu may shed light on its improved application to clinical tumor treatment.
Ectogenesis: understanding opportunities, implications, concerns, and ways forward
Authors: Okesanya Olalekan J. , Gacutno-Evardone Angelica J. , Olaniyi Abideen A. , Hassan Hakeem K. , Gacutno Kristine J. A. , Olaleke Noah O. , Adesola Ridwan O. , Lasala Jose J. , Manirambona Emery , Lucero-Prisno Don E.
Published: January 2024

Ectogenesis is the practice of developing organisms in artificial settings, with applications that range from improving the outcomes of preterm babies to treating fertility issues. It was unveiled in 2017 and provides possibilities for both partial and full ectogenesis while sustaining fetal lambs with concepts like the biobag. Utilizing biobag artificial uteri, complete ectogenesis is the confinement of a woman’s pregnancy in an artificial womb from the inception of the embryonic stage to full gestation; while partial ectogenesis is the utilization of a biobag artificial uterus to continue gestation ex-utero. Ectogenesis may have advantages, but there are concerns about how it will affect children’s social and psychological development. It can benefit biological parenthood, newborn care, fetal therapy, maternal-fetal disputes, societal growth, reduce health risks, and alter cultural norms while promoting reproductive equity. Due to possible risks, rigorous research on human subjects is required before ectogenesis may be implemented. The paper seeks to provide a thorough study for society’s conversation and deliberation, examining its potential advantages as well as its technical, ethical, and regulatory elements.
One-Year Results of a Phase I/II Randomized, Double-Masked, Placebo-Controlled Study of Processed Amniotic Fluid Drops After PRK
Authors: Kirschenbaum Malka Davina , Hu Katherine S. , Ip Colin S. , Lin Amy , Pierce Jan , Holubkov Richard , Jensen Hailey , Mifflin Mark D.
Published: January 2024

Purpose:

The aim of this study was to evaluate the 1-year outcomes of using processed amniotic fluid (pAF) postoperatively after photorefractive keratectomy (PRK).

Methods:

Sixty-one participants were randomized to receive either placebo or pAF drops. The drops were instilled 4 times daily for 1 week after PRK along with routine postoperative medications. The primary outcome measures included uncorrected visual acuity, topographic corneal irregularity measurement, and surface staining over 1 year.

Results:

A statistically significant difference in uncorrected distance visual acuity between the placebo and treatment groups was seen at 1 month post-PRK, with a visual advantage evident in the pAF group. A suggestive difference in corneal irregularity measurement was also seen between the placebo and treatment groups at 1 month postsurgery, with less irregularity noted in the pAF group. No differences in uncorrected distance visual acuity or corneal irregularity measurement were found at 3, 6, and 12 months. There was also no significant difference in corneal staining scores between the 2 groups at any of the measured time points.

Conclusions:

This 1-year study evaluating the safety and efficacy of pAF as an additional postoperative topical medication after PRK demonstrated that pAF offered a mild visual advantage at 1 month post-PRK. There were no late adverse events, and the intervention proved safe at 1 year.
Topical Losartan Inhibition of Myofibroblast Generation in Rabbit Corneas With Acute Incisions
Authors: Martinez Valeria Villabona , Dutra Barbara Araujo Lima , Sampaio Lycia Pedral , Shiju Thomas Michael , Santhiago Marcony R. , Wilson Steven E.
Published: January 2024

Purpose:

The purpose of this study was to study whether deep central corneal incisions close during topical losartan treatment and the effect of topical losartan on myofibroblast generation after incisions in rabbit corneas.

Methods:

Rabbits (12) had a 0.35-mm deep radial incision from the center of the cornea into the limbus in 1 eye that was approximated with a single 10-0 nylon suture 1 mm inside the limbus. The incision was treated with 50 μL of topical 0.8 mg/mL losartan or 50 μL of balanced salt solution vehicle 6 times per day for 1 month. Standardized slitlamp photographs of the central incisions were analyzed for opacity with ImageJ before euthanasia. Triplex IHC was performed on cryofixed corneas for myofibroblast marker alpha-smooth muscle actin, mesenchymal cell marker vimentin, and basement membrane marker laminin alpha-5. Stromal α-SMA–positive myofibroblasts surrounding the incisions were quantitated with ImageJ.

Results:

Topical losartan compared with vehicle did not affect closure of the radial incisions or the opacity that developed surrounding the incisions at 1 month after injury. Topical losartan compared with vehicle did significantly decrease the average density of stromal myofibroblasts surrounding the incisions.

Conclusions:

Topical losartan, a known inhibitor of transforming growth factor beta signaling, did not affect closure of deep corneal incisions. Losartan decreased myofibroblast generation surrounding nearly full-thickness radial corneal incisions compared with vehicle. The opacity at the incisions was not significantly affected by losartan—likely because corneal fibroblasts that develop in the stroma adjacent to the incisions were not changed by the losartan compared with the vehicle.
ECPELLA: Beyond a Left Ventricular Venting Strategy When to Unload the Left Ventricle and How to Decide
Authors: Kuckelman John , Coffey Phil , Sharkawi Musa , Bailey Caryl , Hiner Evan , Patel Vijay
Published: January 2024

Left ventricular (LV) unloading has been shown to improve survival for patients requiring veno-arterial extracorporeal membrane oxygenation (VA ECMO) support for cardiogenic shock. A mortality benefit has been shown for ECMO and concomitant placement of a transcatheter unloading LV pump such as an Impella device (colloquially referred to as ECPELLA or ECMELLA) for patients resuscitated with VA ECMO after a short period of cardiac arrest. Despite the described benefit of LV unloading with VA ECMO for cardiopulmonary resuscitation, it remains unclear as to what criteria should be used and what other diagnostic and therapeutic adjuncts may be useful. We describe here the successful utilization of concomitant VA ECMO and Impella in a 43 year old male with acute heart failure and cardiac arrest. Distinguishing itself from the currently reported methods, our methodology incorporates transesophageal echocardiography (TEE) in the emergency department for rapid decision-making in addition to an automatic chest compression device, the Lund University Cardiac Assist System (LUCAS) device (Stryker, Portage, MI) as a bridge to LV unloading in a hybrid operating suite.
Colorectal Neoplasia in Asian Americans Undergoing First Time Asymptomatic Average-risk Screening Colonoscopies
Authors: Chen Brendan , Hsia Katie , Loscalzo Kirsten , Fai Caitlin , Gupta Samir , Jangi Sushrut
Published: January 2024

Goals:

We identified the prevalence and subtype of colorectal neoplasia removed during index screening colonoscopies in a large Asian American population.

Background:

Asian Americans are the fastest growing demographic group in the United States yet there is a paucity of data on the characteristics of colorectal neoplasia found in this cohort.

Study:

Cross-sectional study of 2208 index colonoscopies performed on average-risk Asian and White patients at a large, tertiary academic center. Patients were identified via diagnostic or procedure codes between 2015 and 2020, with retrospective classification of polyp histopathology. Univariate and multivariate analysis were performed to identify risk factors associated with colorectal neoplasia.

Results:

A total of 2208 patients were identified, of which 1085 were Asian. When adjusted for age and sex, Asians were as likely as Whites to have any type of colorectal neoplasia [44.2% vs. 43.5%, odds ratio (OR)=0.93, (CI: 0.78-1.11)]. On multivariate analysis, Asians were less likely to have sessile serrated polyps (5.5% vs. 9.9%, OR=0.53, 95% CI: 0.38-0.73) and more likely to have tubular adenomas in the left colon (22.6% vs. 18.0%, OR=1.33, 95% CI: 1.08-1.64) compared with Whites.

Conclusions:

Quality measures, such as sessile serrated polyp detection rates, may need to take into account demographic factors such as race. The prevalence of colorectal neoplasia among Asian Americans is substantial and warrants efforts to promote optimal uptake of colorectal cancer screening tests.
PCSK9-directed therapies: an update
Authors: Katzmann Julius L. , Laufs Ulrich
Published: January 2024

Purpose of review

Two large cardiovascular outcomes trials of monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) demonstrated that therapeutic inhibition of extracellular PCSK9 markedly reduces LDL cholesterol concentration and cardiovascular risk. Several novel strategies to inhibit PCSK9 function are in development. Different mechanisms of action may determine specific properties with potential relevance for patient care.

Recent findings

For the monoclonal antibodies evolocumab und alirocumab as first-generation PCSK9 inhibitors, follow-up data of up to 8 years of exposure complement the information on efficacy and safety available from outcome trials. For the small-interfering RNA inclisiran as second-generation PCSK9 inhibitor, several phase III trials have been published and a cardiovascular outcome trial has completed recruitment and is ongoing. Third-generation PCSK9 inhibitors encompass, among others, orally available drugs such as MK-0616 and the fusion protein lerodalcibep. Additional strategies to inhibit PCSK9 include vaccination and gene editing.

Long-term inhibition of PCSK9 with monoclonal antibodies is safe and conveys sustained cardiovascular benefit. Novel strategies to inhibit PCSK9 function such as orally available drugs, RNA targeting, and one-time treatment with gene editing may further enhance the therapeutic armamentarium and enable novel preventive strategies.
Allogeneic Hematopoietic Cell Transplantation Ameliorated Asymptomatic Granulomatous and Lymphocytic Interstitial Lung Disease in a Patient With XIAP Deficiency
Authors: Oshima Mai , Matsukawa Yukihiro , Ikeda Yuhachi , Sakamoto Kenichi , Taga Takashi , Maruo Yoshihiro
Published: January 2024

X-linked inhibitor of apoptosis protein (XIAP) deficiency is an inborn error of immunity (IEI). Allogeneic hematopoietic cell transplantation (HCT) is currently the only curative therapy available for XIAP deficiency. Granulomatous and lymphocytic interstitial lung disease (GLILD) is a common immune-related lung complication of IEIs. We present a 6-year-old boy with XIAP deficiency and GLILD. Computed tomography showed lung nodes but no symptoms. Before HCT, GLILD was not managed with immunosuppressive therapy, because he was asymptomatic. The HCT procedure was subsequently performed. The post-HCT course was uneventful; follow-up computed tomography on day 46 showed nodules had disappeared. HCT could potentially ameliorate GLILD like other inflammatory processes associated with the underlying IEIs.
A shocking intraoperatively diagnosis of ochronotic knee arthropathy: a case report
Authors: Shashaa Mohammad Nour , Alkarrash Mohamad Shadi , Alhasan Yusuf , Kabbany Saad Allah , Rezkallah Vairy , Alhamr Alaa , Al-Araje M. Maher
Published: January 2024

Introduction:

Alkaptonuria is an autosomal extremely rare recessive metabolic disorder with incidence reported to occur as 1:100 000–1:250 000 live births worldwide. This rare metabolic disorder is characterized by the accumulation of homogentisic acid due to a deficiency in homogentisic acid 1,2 dioxygenase. Homogentisic acid subsequently oxidizes and accumulates in the connective tissue. The knee is the most significant peripheral joint to be affected by the disorder. The authors present the first case of ochronotic arthropathy in Syria.

Case presentation:

A 46-year-old male presented with bilateral pain in the knees. the pain was affecting his day-to-day activities, and not responding to conservative management. Anteroposterior standing radiographs demonstrated extensive degenerative disease. Intraoperatively, the diagnosis was done after noticing that the quadriceps tendon and the articular cartilage of the femur, tibia, and patella were blackened during cemented total knee replacement of the knee.

Conclusion:

Ochronotic arthropathy should be kept in mind in middle age patients with severe osteoarthritis to not be surprised by the rare alkaptonuria diagnosis if arthroplasty was indicated.
Creating a New Inframammary Fold, Raising the Breast Footprint, and Elongating the Torso with a Multiplane Concept
Authors: Bark Adel A. , Minikowski Guilherme C. , Moreto Laércio , Mujahed Isaac B. U.
Published: January 2024

Background:

Augmentation mastopexy focuses on restoring the youthful appearance of the female breast. Despite those benefits, there is large scarring to be considered, and the reduction of this side effect is the main goal to enhance the aesthetic result. This article aims to describe a variation of the L-shaped mastopexy technique without complex marking and performed in planes, which brings long-term results for patients undergoing this approach.

Methods:

This was a retrospective observational study based on a series of cases conducted by the author. The preoperative appointment and the surgical technique are described and divided into steps according to their components: cutaneous, glandular tissue, and muscular.

Results:

Between January of 2016 and July of 2021, 632 women underwent surgery. The mean age was 38 years (range, 18 to 71 years). The mean implant volume was 285 cc (range, 175 to 550 cc). All the implants used were round with a nanotextured surface. The mean weight of tissue resected from each breast was 117 g (range, 5 to 550 g). Follow-up ranged from 12 to 84 months, and photographic documentation was performed from 30 days after surgery. Complications totaled 19.30% and were divided into minor (treated with expectant treatment, noninvasive, or with the possibility of correction with local anesthesia), corresponding to 10.44%, and major (in which it was necessary to return to the operating room), corresponding to 8.86%.

Conclusions:

Multiplane L-scar mastopexy is a versatile and safe technique with predictable results, which allow the systematic treatment of the most diverse breast types. Complications are similar to those of other described and solidified techniques.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Direct Repair of Ruptured Nerve Stump to Middle Trunk for Restoration of Extrinsic Finger Extension in Total Brachial Plexus Injuries
Authors: Xue Yunhao , Wang Shufeng , Hu Jingjing , Li Wenjun , Li Feng , Anil Bhatia , Li Pengcheng , Yin Yaobin , Duan Fangfang , Wei Qipei
Published: January 2024

Background:

Attempts to restore independent hand function in total brachial plexus injuries (TBPIs) have often failed due to inconsistent results of finger extension reconstruction. An innovative technique is described to achieve this effect by direct neurorrhaphy of residual (ruptured) roots with the middle trunk.

Methods:

Direct coaptation of the ruptured roots to the middle trunk and, simultaneously, transferring the anterior division of the middle trunk to the posterior division of the lower trunk was performed in 64 patients with TBPI. The return of extension of the elbow, wrist, and fingers was monitored.

Results:

Excellent and good muscle strength of finger extension were noted in 45.3% of cases. The patients were divided into group A (>32 years) and group B (≤32 years) according to receiver operating characteristic curve analysis. The difference of excellent and good rates of finger and wrist extension muscle strengths between the 2 groups was statistically significant (χ2 = 4.635, P = 0.031; χ2 = 6.615, P = 0.010).

Conclusions:

Direct neurorrhaphy of ruptured nerve root stumps with the middle trunk could achieve satisfactory results for finger extension in TBPI for patients ≤32 years old. Long nerve defects (4 to 6.5 cm) could be overcome by freeing the nerve and adducting the arm against the trunk.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.