bluuebunny/crossref_metadata_2025 huggingface dataset:
The Stability of Relativistic Fluids in Linearly Expanding Cosmologies
Authors: Fajman David , Ofner Maximilian , Oliynyk Todd A , Wyatt Zoe
Published: October 2023

In this paper, we study cosmological solutions to the Einstein–Euler equations. We first establish the future stability of nonlinear perturbations of a class of homogeneous solutions to the relativistic Euler equations on fixed linearly expanding cosmological spacetimes with a linear equation of state $p=K \rho $ for the parameter values $K \in (0,1/3)$. This removes the restriction to irrotational perturbations in earlier work [ 15] and relies on a novel transformation of the fluid variables that is well-adapted to Fuchsian methods. We then apply this new transformation to show the global regularity and stability of the Milne spacetime under the coupled Einstein–Euler equations, again with a linear equation of state $p=K \rho $, $K \in (0,1/3)$. Our proof requires a correction mechanism to account for the spatially curved geometry. In total, this is indicative that structure formation in cosmological fluid-filled spacetimes requires an epoch of decelerated expansion.
Pivotal trial of a deep-learning-based retinal biomarker (Reti-CVD) in the prediction of cardiovascular disease: data from CMERC-HI
Authors: Lee Chan Joo , Rim Tyler Hyungtaek , Kang Hyun Goo , Yi Joseph Keunhong , Lee Geunyoung , Yu Marco , Park Soo-Hyun , Hwang Jin-Taek , Tham Yih-Chung , Wong Tien Yin , Cheng Ching-Yu , Kim Dong Wook , Kim Sung Soo , Park Sungha
Published: October 2023

Objective

The potential of using retinal images as a biomarker of cardiovascular disease (CVD) risk has gained significant attention, but regulatory approval of such artificial intelligence (AI) algorithms is lacking. In this regulated pivotal trial, we validated the efficacy of Reti-CVD, an AI-Software as a Medical Device (AI-SaMD), that utilizes retinal images to stratify CVD risk.

Materials and Methods

In this retrospective study, we used data from the Cardiovascular and Metabolic Diseases Etiology Research Center-High Risk (CMERC-HI) Cohort. Cox proportional hazard model was used to estimate hazard ratio (HR) trend across the 3-tier CVD risk groups (low-, moderate-, and high-risk) according to Reti-CVD in prediction of CVD events. The cardiac computed tomography-measured coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and brachial-ankle pulse wave velocity (baPWV) were compared to Reti-CVD.

Results

A total of 1106 participants were included, with 33 (3.0%) participants experiencing CVD events over 5 years; the Reti-CVD-defined risk groups (low, moderate, and high) were significantly associated with increased CVD risk (HR trend, 2.02; 95% CI, 1.26-3.24). When all variables of Reti-CVD, CAC, CIMT, baPWV, and other traditional risk factors were incorporated into one Cox model, the Reti-CVD risk groups were only significantly associated with increased CVD risk (HR = 2.40 [0.82-7.03] in moderate risk and HR = 3.56 [1.34-9.51] in high risk using low-risk as a reference).

Discussion

This regulated pivotal study validated an AI-SaMD, retinal image-based, personalized CVD risk scoring system (Reti-CVD).

Conclusion

These results led the Korean regulatory body to authorize Reti-CVD.
Design of an interface to communicate artificial intelligence-based prognosis for patients with advanced solid tumors: a user-centered approach
Authors: Staes Catherine J , Beck Anna C , Chalkidis George , Scheese Carolyn H , Taft Teresa , Guo Jia-Wen , Newman Michael G , Kawamoto Kensaku , Sloss Elizabeth A , McPherson Jordan P
Published: October 2023

Objectives

To design an interface to support communication of machine learning (ML)-based prognosis for patients with advanced solid tumors, incorporating oncologists’ needs and feedback throughout design.

Materials and Methods

Using an interdisciplinary user-centered design approach, we performed 5 rounds of iterative design to refine an interface, involving expert review based on usability heuristics, input from a color-blind adult, and 13 individual semi-structured interviews with oncologists. Individual interviews included patient vignettes and a series of interfaces populated with representative patient data and predicted survival for each treatment decision point when a new line of therapy (LoT) was being considered. Ongoing feedback informed design decisions, and directed qualitative content analysis of interview transcripts was used to evaluate usability and identify enhancement requirements.

Results

Design processes resulted in an interface with 7 sections, each addressing user-focused questions, supporting oncologists to “tell a story” as they discuss prognosis during a clinical encounter. The iteratively enhanced interface both triggered and reflected design decisions relevant when attempting to communicate ML-based prognosis, and exposed misassumptions. Clinicians requested enhancements that emphasized interpretability over explainability. Qualitative findings confirmed that previously identified issues were resolved and clarified necessary enhancements (eg, use months not days) and concerns about usability and trust (eg, address LoT received elsewhere). Appropriate use should be in the context of a conversation with an oncologist.

Conclusion

User-centered design, ongoing clinical input, and a visualization to communicate ML-related outcomes are important elements for designing any decision support tool enabled by artificial intelligence, particularly when communicating prognosis risk.
Prediction of Surgical Upstaging Risk of Ductal Carcinoma In Situ Using Machine Learning Models
Authors: Hashiba Kimberlee A , Mercaldo Sarah , Venkatesh Sheila L , Bahl Manisha
Published: October 2023

Objective

The purpose of this study was to build machine learning models to predict surgical upstaging risk of ductal carcinoma in situ (DCIS) to invasive cancer and to compare model performance to eligibility criteria used by the Comparison of Operative versus Monitoring and Endocrine Therapy (COMET) active surveillance trial.

Methods

Medical records were retrospectively reviewed of all women with DCIS at core-needle biopsy who underwent surgery from 2007 to 2016 at an academic medical center. Multivariable regression and machine learning models were developed to evaluate upstaging-related features and their performance was compared with that achieved using the COMET trial eligibility criteria.

Results

Of 1387 women (mean age, 57 years; range, 27–89 years), the upstaging rate of DCIS was 17% (235/1387). On multivariable analysis, upstaging-associated features were presentation of DCIS as a palpable area of concern, imaging finding of a mass, and nuclear grades 2 or 3 at biopsy (P < 0.05). If COMET trial eligibility criteria were applied to our study cohort, then 496 women (42%, 496/1175) would have been eligible for the trial, with an upstaging rate of 12% (61/496). Of the machine learning models, none had a significantly lower upstaging rate than 12%. However, if using the models to determine eligibility, then a significantly larger proportion of women (56%–87%) would have been eligible for active surveillance.

Conclusion

Use of machine learning models to determine eligibility for the COMET trial identified a larger proportion of women eligible for surveillance compared with current eligibility criteria while maintaining similar upstaging rates.
Reduction of genetic diversity in ‘Alalā (Hawaiian crow; Corvus hawaiiensis) between the late 1800s and the late 1900s
Authors: Blanchet Geneviève , Bellinger M Renee , Kearns Anna M , Cortes-Rodriguez Nandadevi , Masuda Bryce , Campana Michael G , Rutz Christian , Fleischer Robert C , Sutton Jolene T
Published: October 2023

Genetic and genomic data are increasingly used to aid conservation management of endangered species by providing insights into evolutionary histories, factors associated with extinction risks, and potential for future adaptation. For the ‘Alalā, or Hawaiian crow (Corvus hawaiiensis), genetic concerns include negative correlations between inbreeding and hatching success. However, it is unclear if low genetic diversity and inbreeding depression are consequences of a historical population bottleneck, or if ‘Alalā had historically low genetic diversity that predated human influence, perhaps as a result of earlier declines or founding events. In this study, we applied a hybridization-based sequence capture to generate a genome-wide single nucleotide polymorphism (SNP) dataset for comparing historical specimens collected in the 1890s, when ‘Alalā were more numerous, to samples taken between 1973 and 1998, when ‘Alalā population densities were near the lowest documented levels in the wild, prior to all individuals being collected for captive rearing. We found low genome-wide diversity in both sample groups, however, the modern sample group (1973 to 1998 cohort) exhibited relatively fewer polymorphic alleles, a lower proportion of polymorphic loci, and lower observed heterozygosity, consistent with a population decline and potential bottleneck effects. These results combined with a current low population size highlight the importance of continued efforts by conservation managers to mitigate inbreeding and maintain founder representation to preserve what genetic diversity remains.
Loss of feedback regulation between FAM3B and androgen receptor driving prostate cancer progression
Authors: Ma Tianfang , Jin Lianjin , Bai Shanshan , Liu Zhan , Wang Shuo , Shen Beibei , Cho Yeyoung , Cao Subing , Sun Meijuan J S , Fazli Ladan , Zhang David , Wedderburn Chiyaro , Zhang Derek Y , Mugon Gavisha , Ungerleider Nathan , Baddoo Melody , Zhang Kun , Schiavone Lovisa Holmberg , Burkhardt Brant R , Fan Jia , You Zongbing , Flemington Erik K , Dong Xuesen , Dong Yan
Published: October 2023

Background

Although the fusion of the transmembrane serine protease 2 gene (TMPRSS2) with the erythroblast transformation-specific-related gene (ERG), or TMPRSS2-ERG, occurs frequently in prostate cancer, its impact on clinical outcomes remains controversial. Roughly half of TMPRSS2-ERG fusions occur through intrachromosomal deletion of interstitial genes and the remainder via insertional chromosomal rearrangements. Because prostate cancers with deletion-derived TMPRSS2-ERG fusions are more aggressive than those with insertional fusions, we investigated the impact of interstitial gene loss on prostate cancer progression.

Methods

We conducted an unbiased analysis of transcriptome data from large collections of prostate cancer samples and employed diverse in vitro and in vivo models combined with genetic approaches to characterize the interstitial gene loss that imposes the most important impact on clinical outcome.

Results

This analysis identified FAM3B as the top-ranked interstitial gene whose loss is associated with a poor prognosis. The association between FAM3B loss and poor clinical outcome extended to fusion-negative prostate cancers where FAM3B downregulation occurred through epigenetic imprinting. Importantly, FAM3B loss drives disease progression in prostate cancer. FAM3B acts as an intermediator of a self-governing androgen receptor feedback loop. Specifically, androgen receptor upregulates FAM3B expression by binding to an intronic enhancer to induce an enhancer RNA and facilitate enhancer-promoter looping. FAM3B, in turn, attenuates androgen receptor signaling.

Conclusion

Loss of FAM3B in prostate cancer, whether through the TMPRSS2-ERG translocation or epigenetic imprinting, causes an exit from this autoregulatory loop to unleash androgen receptor activity and prostate cancer progression. These findings establish FAM3B loss as a new driver of prostate cancer progression and support the utility of FAM3B loss as a biomarker to better define aggressive prostate cancer.
Astaxanthin protects against pirarubicin-induced H9c2 cardiomyocytes by adjusting microRNA-494-3p-mediated MDM4/p53 signalling pathway
Authors: Huang Peng , Zhang Yibing , Wang Fengjun , Qin Meng , Ma Jiulong , Ji Jiahua , Wei Dexian , Ren Liqun
Published: October 2023

Purpose

Pirarubicin (THP) is an antitumour drug widely used in clinical practice, but its cardiotoxicity limits its application. THP cardiotoxicity must be treated as soon as possible. There is an urgent need to find drugs that alleviate THP cardiotoxicity. The purpose of this study was to investigate the effects and mechanisms of Astaxanthin (AST) on THP-induced cardiomyocytes.

Methods

Rat cardiomyocytes H9c2 were induced with THP. The effects of AST on THP-induced H9c2 and its mechanism were investigated by CCK8, reactive oxygen species assay, tunnel assay, flow cytometry, RT-qPCR, and Western blot.

Results

AST increased cell viability, inhibited apoptosis and accelerated cell cycle progression, reduced oxidative damage and inflammatory response in THP-induced H9c2; down-regulated miR-494-3p expression, promoted MDM4 expression, inhibited p53 activation, and suppressed apoptosis-related protein expression. Overexpression of MiR-494-3p reversed the above effects of AST.

Conclusions

AST can inhibit H9c2 apoptosis induced by THP and attenuate H9c2 damage by THP, which may be achieved by downregulating miR-494-3p, upregulating MDM4, and inhibiting p53.
Current status of remote radiotherapy treatment planning in Japan: findings from a national survey
Authors: Saito Masahide , Tamamoto Tetsuro , Kawashiro Shohei , Umezawa Rei , Matsuda Masaki , Tohyama Naoki , Katsuta Yoshiyuki , Kanai Takayuki , Nemoto Hikaru , Onishi Hiroshi
Published: October 2023

The purpose of this study was to investigate the status of remote-radiotherapy treatment planning (RRTP) in Japan through a nationwide questionnaire survey. The survey was conducted between 29 June and 4 August 2022, at 834 facilities in Japan that were equipped with linear accelerators. The survey utilized a Google form that comprised 96 questions on facility information, information about the respondent, utilization of RRTP between facilities, usage for telework and the inclination to implement RRTPs in the respondent’s facility. The survey analyzed the utilization of the RRTP system in four distinct implementation types: (i) utilization as a supportive facility, (ii) utilization as a treatment facility, (iii) utilization as a teleworker outside of the facility and (iv) utilization as a teleworker within the facility. The survey response rate was 58.4% (487 facilities responded). Among the facilities that responded, 10% (51 facilities) were implementing RRTP. 13 served as supportive facilities, 23 as treatment facilities, 17 as teleworkers outside of the facility and 5 as teleworkers within the facility. In terms of system usage between supportive and treatment facilities, 70–80% of the participants utilized the system for emergencies or as overtime work for external workers. A substantial number of facilities (38.8%) reported that they were unfamiliar with RRTP implementation. The survey showed that RRTP utilization in Japan is still limited, with a significant number of facilities unfamiliar with the technology. The study highlights the need for greater understanding and education about RRTP and financial funds of economical compensation.
How do brassinosteroids fit in bud outgrowth models?
Authors: Kelly Jack H , Brewer Philip B
Published: October 2023

A network of plant hormonal signals coordinates plant branching. Brassinosteroids are important in this network, acting as repressors of the strigolactone pathway and TEOSINTE BRANCHED1 .
Galaxy And Mass Assembly: the xSAGA galaxy complement in nearby galaxy groups
Authors: Holwerda B W , Phillipps S , Weerasooriya S , Bovill M S , Brough S , Brown M J I , Robertson C , Cook K
Published: October 2023

Groups of galaxies are the intermediate density environment in which much of the evolution of galaxies is thought to take place. In spectroscopic redshift surveys, one can identify these as close spatial-redshift associations. However, spectroscopic surveys will always be more limited in luminosity and completeness than imaging ones. Here, we combine the Galaxy And Mass Assembly (GAMA) group catalogue with the extended Satellites Around Galactic Analogues (xSAGA) catalogue of machine learning identified low-redshift satellite galaxies. We find 1825 xSAGA galaxies within the bounds of the GAMA equatorial fields (mr < 21), 1562 of which could have a counterpart in the GAMA spectroscopic catalogue (mr < 19.8). Of these, 1326 do have a GAMA counterpart with 974 below z = 0.03 (true positives) and 352 above z = 0.03 (false positives). By cross-correlating the GAMA group catalogue with the xSAGA catalogue, we can extend and characterize the satellite content of GAMA galaxy groups. We find that most groups have <5 xSAGA galaxies associated with them, but richer groups may have more. Each additional xSAGA galaxy contributes only a small fraction of the group’s total stellar mass (${\ll}10$ per cent). Selecting GAMA groups that resemble the Milky Way halo, with a few (<4) bright galaxies, we find that xSAGA can add a magnitude fainter sources to a group and that the Local Group does not stand out in the number of bright satellites. We explore the quiescent fraction of xSAGA galaxies in GAMA groups and find a good agreement with the literature.
Disingenuous Infallibilism
Authors: Fantl Jeremy
Published: October 2023

Some recent epistemologists propose that certainty is the norm of action and assertion. This proposal is subject to skeptical worries. If, as is usually supposed, certainty is very hard to come by, legitimate action and assertion will be rare. To remedy this, some have conjoined their certainty-norms with a context-sensitive semantics for ‘certainty’. For a proposition to be certain for you, you only need to be able to exclude relevant alternatives. I argue that, depending on what makes an alternative relevant, this kind of view is disingenuous. In particular, if an alternative can be made relevant by being relevant to rational action, it allows an escape from the skeptical consequences only by licensing David Lewis-style utterances of the form, “You know that p only if there is no probability, no matter how small, that not-p—Psst!—Unless that probability is really small.” While there are legitimate ways to exclude some possibilities from relevance, it is disingenuous, I argue, to exclude possibilities from relevance on the basis of the very characteristic—low but nonzero probability—that is claimed to be incompatible with certainty.
Ectopic Expression of Distinct PLC Genes Identifies ‘Compactness’ as a Possible Architectural Shoot Strategy to Cope with Drought Stress
Authors: van Hooren Max , van Wijk Ringo , Vaseva Irina I , Van Der Straeten Dominique , Haring Michel , Munnik Teun
Published: October 2023

Phospholipase C (PLC) has been implicated in several stress responses, including drought. Overexpression (OE) of PLC has been shown to improve drought tolerance in various plant species. Arabidopsis contains nine PLC genes, which are subdivided into four clades. Earlier, OE of PLC3, PLC5 or PLC7 was found to increase Arabidopsis’ drought tolerance. Here, we confirm this for three other PLCs: PLC2, the only constitutively expressed AtPLC; PLC4, reported to have reduced salt tolerance and PLC9, of which the encoded enzyme was presumed to be catalytically inactive. To compare each PLC and to discover any other potential phenotype, two independent OE lines of six AtPLC genes, representing all four clades, were simultaneously monitored with the GROWSCREEN-FLUORO phenotyping platform, under both control- and mild-drought conditions. To investigate which tissues were most relevant to achieving drought survival, we additionally expressed AtPLC5 using 13 different cell- or tissue-specific promoters. While no significant differences in plant size, biomass or photosynthesis were found between PLC lines and wild-type (WT) plants, all PLC-OE lines, as well as those tissue-specific lines that promoted drought survival, exhibited a stronger decrease in ‘convex hull perimeter’ (= increase in ‘compactness’) under water deprivation compared to WT. Increased compactness has not been associated with drought or decreased water loss before although a hyponastic decrease in compactness in response to increased temperatures has been associated with water loss. We propose that the increased compactness could lead to decreased water loss and potentially provide a new breeding trait to select for drought tolerance.
The role of the pigment–protein complex LHCBM1 in nonphotochemical quenching in Chlamydomonas reinhardtii
Authors: Liu Xin , Nawrocki Wojciech J , Croce Roberta
Published: October 2023

Nonphotochemical quenching (NPQ) is the process that protects photosynthetic organisms from photodamage by dissipating the energy absorbed in excess as heat. In the model green alga Chlamydomonas reinhardtii, NPQ is abolished in the knock-out mutants of the pigment–protein complexes LHCSR3 and LHCBM1. However, while LHCSR3 is a pH sensor and switches to a quenched conformation at low pH, the role of LHCBM1 in NPQ has not been elucidated yet. In this work, we combined biochemical and physiological measurements to study short-term high-light acclimation of npq5, the mutant lacking LHCBM1. In low light in the absence of this complex, the antenna size of PSII was smaller than in its presence; this effect was marginal in high light (HL), implying that a reduction of the antenna was not responsible for the low NPQ. The mutant expressed LHCSR3 at the wild-type level in HL, indicating that the absence of this complex is also not the reason. Finally, NPQ remained low in the mutant even when the pH was artificially lowered to values that can switch LHCSR3 to the quenched conformation. We concluded that both LHCSR3 and LHCBM1 are required for the induction of NPQ and that LHCBM1 is the interacting partner of LHCSR3. This interaction can either enhance the quenching capacity of LHCSR3 or connect this complex with the PSII supercomplex.
Increasing buprenorphine access for patients with chronic pain: a quality improvement initiative
Authors: Wesolowicz Danielle M , Spelman Juliette F , Edmond Sara N , Schwartz Amy R , Kravetz Jeffrey D , Edens Ellen L , Becker William C
Published: October 2023

Objective

Buprenorphine is effective for chronic pain and safer than full-agonist opioids; however, limited education about and support for buprenorphine can result in under-prescribing in primary care and reduced access in specialty pain clinics. The purpose of this quality improvement initiative was to optimize and evaluate procedures for transferring patients stable on buprenorphine for chronic pain from a specialty pain clinic back to primary care.

Setting

Eight primary care clinics within a Veterans Health Administration health care system.

Methods

A standard operating procedure for facilitated transfer of prescribing was developed after a needs assessment and was introduced during an educational session with primary care providers, and providers completed a survey assessing attitudes about buprenorphine prescribing. Success of the initiative was measured through the number of patients transferred back to primary care over the course of 18 months.

Results

Survey results indicated that primary care providers with previous experience prescribing buprenorphine were more likely to view buprenorphine prescribing for pain as within the scope of their practice and to endorse feeling comfortable managing a buprenorphine regimen. Providers identified systemic and educational barriers to prescribing, and they identified ongoing support from specialty pain care and primary care as a facilitator of prescribing. Metrics suggested that the standard operating procedure was generally successful in transferring and retaining eligible patients in primary care.

Conclusion

This quality improvement initiative suggests that a facilitated transfer procedure can be useful in increasing buprenorphine prescribing for pain in primary care. Future efforts to increase primary care provider comfort and address systemic barriers to buprenorphine prescribing are needed.
Exploiting hysteresis in coordination incentives for cost-effective biodiversity conservation
Authors: Drechsler Martin , Grimm Volker
Published: October 2023

Conservation payment schemes, typically spatially homogenous, are widely used to induce biodiversity-friendly land use. They can also address habitat fragmentation if a bonus is added to the homogenous base payment when conservation measures are implemented next to other conserved lands. However, if conservation costs differ spatially, the spatial aggregation of habitat can be costly, and the cost-effective generation of contiguous habitats is an issue. Here, we use a stylised agent-based simulation model to demonstrate that land use induced by agglomeration bonus schemes can exhibit hysteresis, meaning that the amount and aggregation of conservation is to some extent resilient to changes in payment levels. This suggests that staggered payment schemes in which a relative large bonus is used to establish a habitat network and lowered afterwards to a level sufficient to sustain the habitat network, may be more cost-effective than a scheme with a constant bonus. We show that low base payments and relatively high bonuses can create hysteresis, and staggered payments based on this design principle can—especially at high spatial variation of conservation costs and long-term time preference in the decision maker—generate cost-effectiveness gains.
Nanoencapsulation of carotenoid extract via the temperature-induced phase transition of triblock polymer in supercritical carbon dioxide
Authors: Wosu Chiziezi I , Harvey Patricia J , Trivedi Vivek
Published: October 2023

Objectives

Carotenoids are increasingly explored as nutraceuticals, but their low bioavailability due to poor aqueous solubility limits their applications. This study discusses the development of a novel and organic solvent-free method to develop carotenoid-containing polymeric nanoparticles via temperature-induced phase transition (TIPT) of pluronic F-68 to obtain formulations with the improved dissolution of carotenoids.

Methods

The nanoencapsulation of carotenoids in pluronic F-68 was performed in supercritical carbon dioxide (scCO2) to avoid oxidative or temperature/solvent-induced degradation. The nanoencapsulates were prepared in scCO2 at 40°C or 60°C and 10 MPa without the aid of any organic solvent. The formulations thereafter were characterised for particle size via dynamic light scattering, particle morphology via scanning electron microscopy and carotenoid content/release via high-performance liquid chromatography (HPLC).

Key findings

HPLC results showed carotenoid degradation to be negligible in freshly prepared formulations when prepared in scCO2 at 60°C and 10 MPa. The developed particles were spheroidal with sizes ranging between 150 and 250 nm depending on carotenoid content in the preparation. An improvement in the aqueous solubility and storage stability (5°C) of carotenoids was also observed for the formulations prepared in scCO2.

Conclusions

These results suggest that TIPT under scCO2 can be applied to formulate nanoparticulates with improved dissolution rate and stability of thermosensitive molecules such as carotenoids without causing any degradation during the processing.
Correlation between bone mineral density and bone metabolic markers in postmenopausal women with osteoporotic fractures at different C-terminal telopeptide of type 1 collagen levels: a retrospective analysis study
Authors: Zhu Xiaonan , Chen Lin , Pan Ling , Zeng Yuexi , Fu Qiang , Liu Yanbin , Peng Yongde , Wang Yufan , You Li
Published: October 2023

Objective

This study aimed to analyze the correlation between bone mineral density (BMD) and bone resorption markers in postmenopausal women with osteoporosis fractures and identify risk factors for second fractures.

Methods

This retrospective analysis of 1,239 older women with fractures with a median age of 70 years who attended Shanghai General Hospital from January 2007 to December 2016, included a first fracture group (1,008 cases) and a second fractures group (231 cases). The risk factors for fractures were analyzed by comparing these groups on clinical characteristics, BMD, and bone metabolism markers stratified by quartiles of serum C-terminal telopeptide of type 1 collagen (CTX). Binary logistic regression analysis was used to identify risk factors for second fractures.

Results

In the whole sample, BMD was negatively correlated with age and serum osteocalcin and positively correlated with body mass index (BMI). In women with first fractures, those in the highest quartile of serum CTX had the lowest spine and hip BMD. Second fractures were significantly associated with BMI, lower spine and hip BMD, and higher serum osteocalcin but not CTX. Binary logistic regression analysis showed that high BMI (odds ratio [OR], 1.08 [95% CI, 1.03-1.14]; P = 0.001), low lumbar BMD (OR, 0.24 [95% CI, 0.07-0.82]; P = 0.023), low total hip BMD (OR, 0.05 [95% CI, 0.00-0.88]; P = 0.041), and lack of antiosteoporosis treatment (OR, 2.71 [95% CI, 2.71-4.08]; P < 0.001) were independent risk factors for second fractures.

Conclusions

In older women with fractures, BMD was significantly lower in women with second fractures than in those with first fractures. Higher levels of serum CTX and osteocalcin, which indicates increased bone resorption, were negatively correlated with BMD. In women with a first fracture, serum CTX higher than 605 pg/mL was negatively correlated with BMD, whereas no correlation was found between different CTX and BMD in women with second fractures. High BMI and low BMD as well as not receiving antiosteoporosis treatment were independent risk factors for second fractures.
Comparison of toric intraocular lens alignment between femtosecond laser–assisted capsular marking and digital marking
Authors: Schultz Tim , Hoffmann Sebastian , Dick H. Burkhard
Published: October 2023

Purpose:

To compare the accuracy of toric intraocular lens (IOL) alignment between femtosecond laser–assisted capsular marking and digital marking.

Setting:

Ruhr University Eye Clinic, Bochum, Germany.

Design:

Prospective clinical trial.

Methods:

In this study, 28 eyes of 23 patients, who underwent femtosecond laser–assisted cataract surgery with implantation of a toric IOL, were included. Intraoperatively, both femtosecond laser–assisted capsular marking and digital marking were applied simultaneously and compared in every case. The toric IOL was aligned to the capsular markings. Postoperatively, the axis of the capsular markings and toric IOL alignment was examined. Visual acuity and refractive outcomes were evaluated.

Results:

Both alignment methods were performed without intraoperative complications in all cases. 25 eyes were included in the final analysis. Misalignment was significantly lower with femtosecond laser–assisted capsular marking than with digital marking (1.71 ± 1.25 degrees vs 2.64 ± 1.70 degrees, P = .016). Deviation from the target axis of the toric IOL was 1.62 ± 1.24 degrees 4 to 6 weeks postoperatively. Postoperative uncorrected distance visual acuity was 0.14 ± 0.13 logMAR, and residual astigmatism was 0.3 ± 0.23 diopter (D) with an astigmatism ≤0.5 D in 93% of eyes.

Conclusions:

Both methods showed excellent results for the alignment of toric IOLs. However, femtosecond laser–assisted capsular marking was significantly more precise than digital marking and showed good refractive results. In addition, capsular marking offers the possibility to avoid parallax error and evaluating postoperative IOL rotation.
Multidermatomal herpes zoster triggered by psychological stress in an immunocompetent young adult: a rare case report and clinical insights
Authors: Yogi Tek N. , Bhusal Amrit , Subedi Suman , Katwal Shailendra , Acharya Kshitiz
Published: October 2023

Introduction and Importance:

Herpes zoster (HZ), a reactivated varicella zoster virus infection arising from dormant viral latency after initial chickenpox, manifests as localized skin rashes along dermatomes. Multidermatomal involvement, especially in immunocompetent individuals, is rare. The potential link between psychological stress and HZ reactivation remains underexplored. The authors present a case of multidermatomal HZ triggered by psychological stress in a young immunocompetent adult.

Case presentation:

A 26-year-old male presented with vesicular lesions spanning C5, C8, T1, and T2 dermatomes, triggered by psychological stress. The disease exhibited a unique midline-crossing presentation. The Varicella zoster virus IgM test result was positive. Treatment included acyclovir, pain management, and stress reduction strategies, yielding complete resolution within 3 weeks.

Clinical discussions:

The case highlights a distinctive multidermatomal HZ presentation, defying conventional dermatomal restrictions. Psychological stress potentially influenced viral reactivation. Immunocompetence and stress interplay merit further exploration. Multidermatomal HZ necessitates prompt clinical recognition and comprehensive evaluation. Antiviral therapy and integrated stress management may contribute to successful outcomes.

Conclusion:

This case underscores the rare occurrence of multidermatomal HZ in an immunocompetent young adult triggered by psychological stress. The atypical presentation and potential role of stress in viral reactivation emphasize the complex interaction between the nervous and immune systems. Integrated clinical management, stress reduction strategies, and antiviral therapy were effective in resolving the condition. Further research is warranted to elucidate the mechanisms underlying stress-induced viral reactivation and its clinical implications.
Antiretroviral drug use and the risk of falls in people living with HIV: a systematic review and meta-analysis
Authors: Lamichhane Pratik , Koutentakis Michail , Rathi Sushma , Ode Ayomide D. , Trivedi Hirak , Zafar Summiya , Lamichhane Pratima , Gupta Prahlad , Ghimire Rakesh
Published: October 2023

Objective:

The risk of falls in people living with HIV (PLHIVs) on antiretroviral therapy (ART) has received little attention in the literature. The aim of the meta-analysis is to quantify the association between fall risk and various categories of drugs used in ART.

Material and Methods:

PubMed, Google Scholar, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched from inception to January 2023. Any observational study or controlled trial that reported on the relationship of at least one antiretroviral drug with falls in PLHIVs was included. Data on the frequency of single fallers, multiple fallers (≥2 falls), and non-fallers were extracted and studied for each drug and drug category. The pooled results were reported as an odds ratio (OR) with a 95% confidence interval (CI).

Results:

A total of five observational studies (51 675 participants) were included out of 414 articles obtained through a literature review. Stavudine use was found to be associated with an increased risk of single falls in PLHIVs (OR: 1.69, 95% CI: 1.08–2.66, P=0.02). However, efavirenz (OR: 0.82, 95% CI=0.76–0.89, P<0.001) and zidovudine (OR: 0.82, 95% CI=0.77–0.92, P<0.001) were found protective against the single falls. Didanosine had no significant association with fall risk (OR: 1.23, 95% CI: 0.78–1.93, P=0.37). Likewise, protease inhibitors, integrase inhibitors, nucleoside reverse transcriptase inhibitors, and non-nucleoside reverse transcriptase inhibitors were discovered to have no significant association with fall risk.

Conclusion:

Most drug categories of ART have no significant association with the risk of falls in PLHIVs. However, certain drugs, such as didanosine and stavudine, which have the inherent effect of causing balance deficits and neuropathy, should be used cautiously.
Fear of a new pandemic: perception and prediction of monkeypox among the middle east general population
Authors: Mahmmoud Fadelallah Eljack Mohammed , Elnaiem Walaa , Abdelwahed Aya Elsayed , Hasabo Elfatih. , Abbas Azza A. , Ahmed Alaa S. , Jobran Afnan W.M. , AbdAlla Mohamed Malaz Tarig , Muhalil Mohammed Gabir , Jagran Idris Leena Mohamed , Bakour Rose Khalid , Eltaib Elseed Lina Zainelabdin , Al Komi Omar , Mugibel Tayba Abdulrahman , Nour Alshareef B. , Ibrahim Howida , Owish Sukar Khalid Abbas , Ahmed Fadi M. Toum , Elkhazin Mohamed Ali Khattab Saeed , Hussien Mohamed Ahmed Khabab Abbasher ,   Middle East Collaborators
Published: October 2023

Background:

Monkeypox is a zoonotic disease caused by the monkeypox virus, an Orthopox virus. The 2022 monkeypox outbreak provoked fear among the public. Public awareness about the disease could be an important factor in its control. The authors conducted this study to assess the perception and prediction of monkeypox among the Middle East public.

Methods:

This cross-sectional study was conducted in August 2022. Data were conveniently collected from eight Middle Eastern countries using an online self-administered questionnaire distributed through educational and social media platforms. Statistical analysis was conducted using R software.

Results:

Approximately 11 016 individuals participated in this study. The participants’ overall knowledge score indicated poor knowledge about monkeypox. Most of the participants knew the causative organism (66.7%). However, numerous participants were not aware of the disease mode of transmission, symptoms, complications, and vaccination. Participants’ awareness was mostly gained from social media (61.8%). The majority predicted acquiring monkeypox when protective measures are not taken (72.7%), progression to a pandemic with economic consequences (50.8 and 52%, respectively), and the ability of the Ministry of Health to control the epidemic (51.5%).

Conclusion:

In the Middle East, public knowledge about monkeypox is poor. Raising awareness about monkeypox would be of benefit in controlling the epidemic. This study constitutes evidence upon which health education programs could be designed.
A rare case of Demons-Meigs’ syndrome with a 7.5 kg giant ovarian fibroma associated with severe dyspnea: case report
Authors: Ali Abdifatah Abdi , Jeannot Baanitse Munihire , Olasinde Anthony Ayotunde , Abdirizak Yusuf , Amin Abdirahin Omar , Muhumuza Joshua , Sikakulya Franck Katembo
Published: October 2023

Introduction and importance:

Demons-Meigs syndrome is a rare condition characterized by the presence of a benign fibroma of the ovary, ascites, and pleural effusion. It is very uncommon, and the diagnosis is made with difficulty based on symptoms that usually mimic disseminated malignancy or tuberculosis, but imaging may confirm the diagnosis. The definitive treatment is laparotomy, after which the symptoms resolve.

Case presentation:

We present a 36-year-old female with Demons-Meigs’ syndrome with severe dyspnea who underwent an abdominal surgical exploration, which revealed ascites of 1500 ml and an ovarian fibroma weighing 7.5 kg and measuring 12 cm in length. There were no postoperative complications. CA-125 was undetectable at 3 months post-procedure.

Clinical discussion:

The most common symptoms are dyspnea, fever, fatigue, and weight loss. In low- and middle-income countries, patients usually present with late-stage disease. The treatment of choice for Demons-Meigs’ syndrome is exploratory laparotomy.

Conclusion:

This tumor is often misdiagnosed as a uterine myoma on sonography. The symptoms resolved, and the patient became asymptomatic after laparotomy and thoracocentesis. For this reason, when patients present with effusion and an abdominal mass, a thorough assessment should be done to confirm if it is Demons-Meigs’ syndrome, which can be completely cured by the removal of the tumor.
Beyond One's Attitude Toward the Self
Authors: Lavi-Rotenberg Adi , Frishman Noa , Igra Libby , Gilboa-Schechtman Eva , Hasson-Ohayon Ilanit
Published: October 2023

Self-stigma is associated with a variety of negative self-perceptions among people coping with schizophrenia, as well as with different aspects of social behaviors. We explored the associations between self-compassion, self-esteem, social anxiety, and self-stigma among people coping with schizophrenia. The baseline data of 56 adults with schizophrenia who were enrolled in a Metacognitive Reflection and Insight Therapy trial were used. Participants filled out self-report questionnaires measuring self-compassion, self-esteem, social anxiety, and self-stigma. Self-esteem and self-compassion were negatively correlated with self-stigma and social anxiety. Self-compassion was not found to contribute beyond self-esteem to the prediction of self-stigma. Importantly, self-esteem and social anxiety were found to mediate the effects of self-compassion on self-stigma. Thus, it seems that social variables, in addition to self-variables, may lead to the formation of self-stigma among people with schizophrenia. Therefore, alongside addressing self-esteem and self-compassion, integrating therapeutic elements related to coping with social anxiety into interventions would seem to be an important factor in reducing self-stigma among people with serious mental illness.
CARD9-Mediated Macrophage Responses and Collagen Fiber Capsule Formation Caused by Textured Breast Implants
Authors: Shoji Miki , Kanno Emi , Tanno Hiromasa , Yamaguchi Kenji , Ishi Sinyo , Takagi Naoyuki , Kurosaka Shiho , Sato Ko , Niiyama Momoko , Ito Akihiko , Ishii Keiko , Imai Yoshimichi , Kawakami Kazuyoshi , Tachi Masahiro
Published: October 2023

Background:

An increasing number of women are undergoing breast implantation for cosmetic purposes or for reconstructive purposes after breast excision. The surface morphology of the breast implant is a key factor associated with the induction of capsule contraction. The effect of surface morphology on the inflammatory response after implant insertion remains unclear, however. The authors conducted comparative analyses to determine the effect of the textured and smooth surface morphology of silicone sheets.

Methods:

Each type of silicone sheet was inserted into the subcutaneous pocket below the panniculus carnosus in C57BL/6 mice and mice with genetic disruption of CARD9, Dectin-1, Dectin-2, or Mincle. The authors analyzed collagen fiber capsule thickness, histologic findings, and macrophage inflammatory response, including transforming growth factor (TGF)–β synthesis.

Results:

The authors found that textured surface morphology contributed to the formation of collagen fiber capsules and the accumulation of fibroblasts and myofibroblasts, and was accompanied by the accumulation of TGF-β–expressing macrophages and foreign-body giant cells. CARD9 deficiency attenuated collagen fiber capsule formation, macrophage responses, and TGF-β synthesis, although the responsible C-type lectin receptors remain to be clarified.

Conclusion:

These results suggest that CARD9 may have a strong impact on silicone sheet morphology through the regulation of macrophage responses.

Clinical Relevance Statement:

Silicone breast implants have been widely used for postmastectomy and cosmetic augmentation mammaplasty breast reconstruction. The authors sought to elucidate the surface morphology of the breast implant as one of the key factors associated with the formation of collagen fiber capsules.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Utilization Trends of Nerve Autograft Alternatives for the Reconstruction of Peripheral Nerve Defects
Authors: Adidharma Widya , Wang Yichu , Kotsis Sandra V. , Wang Lu , Chung Kevin C.
Published: October 2023

Background:

Autologous nerve grafting is the time-honored reconstruction method for peripheral nerve gaps. However, it is associated with donor site morbidities. A growing number of studies have demonstrated the effective use of decellularized nerve allograft and synthetic conduits, which are convenient options with no donor deficit. The specific aim of this study was to characterize changes in practice trends for peripheral nerve defect reconstruction.

Methods:

We queried the 2015-2020 Truven MarketScan database for patients who underwent nerve autograft, allograft, synthetic conduit, and/or vein graft reconstruction. Patient demographic data (i.e. location, indication) and hospital characteristics (i.e. facility, provider type) were recorded. Regression analysis identified changes in trends over the study period.

Results:

4331 patients underwent one or more nerve gap reconstructive procedures over the study period. Since the introduction of allograft CPT code in 2018, segmented mixed effect longitudinal modeling revealed allograft utilization significantly increased from 21.5% to 29.6% after 2018 (p<0.001), whereas nerve autograft utilization decreased from 18.6% to 15.8% and conduit utilization decreased from 60% to 54.7% (p=0.09 and p=0.03, respectively). When stratifying autograft by size, use of autograft ≥4cm significantly decreased from 10.6% to 7.7% after 2018 (p=0.03), and autograft >4cm did not. When stratifying by state, there is heterogeneity in utilizati

Conclusion:

After creation of a designated allograft CPT code in 2018, there was an increase in allograft use with concomitant decrease in conduit and short length autograft use, suggesting that allograft replaced a portion of procedures used in short nerve gap reconstruction.
A Comprehensive Review of Liver Allograft Fibrosis and Steatosis: From Cause to Diagnosis
Authors: Rabindranath Madhumitha , Zaya Rita , Prayitno Khairunnadiya , Orchanian-Cheff Ani , Patel Keyur , Jaeckel Elmar , Bhat Mamatha
Published: October 2023

Despite advances in posttransplant care, long-term outcomes for liver transplant recipients remain unchanged. Approximately 25% of recipients will advance to graft cirrhosis and require retransplantation. Graft fibrosis progresses in the context of de novo or recurrent disease. Recurrent hepatitis C virus infection was previously the most important cause of graft failure but is now curable in the majority of patients. However, with an increasing prevalence of obesity and diabetes and nonalcoholic fatty liver disease as the most rapidly increasing indication for liver transplantation, metabolic dysfunction-associated liver injury is anticipated to become an important cause of graft fibrosis alongside alloimmune hepatitis and alcoholic liver disease.

To better understand the landscape of the graft fibrosis literature, we summarize the associated epidemiology, cause, potential mechanisms, diagnosis, and complications. We additionally highlight the need for better noninvasive methods to ameliorate the management of graft fibrosis. Some examples include leveraging the microbiome, genetic, and machine learning methods to address these limitations. Overall, graft fibrosis is routinely seen by transplant clinicians, but it requires a better understanding of its underlying biology and contributors that can help inform diagnostic and therapeutic practices.