bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel therapeutic targets and emerging treatments for atherosclerotic cardiovascular disease
Authors: Zheng Wayne C , Chan William , Dart Anthony , Shaw James A 
Published: October 2023

Abstract
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality worldwide. Even with excellent control of low-density lipoprotein cholesterol (LDL-C) levels, adverse cardiovascular events remain a significant clinical problem worldwide, including among those without any traditional ASCVD risk factors. It is necessary to identify novel sources of residual risk and to develop targeted strategies that address them. Lipoprotein(a) has become increasingly recognized as a new cardiovascular risk determinant. Large-scale clinical trials have also signalled the potential additive cardiovascular benefits of decreasing triglycerides beyond lowering LDL-C levels. Since CANTOS (Anti-inflammatory Therapy with Canakinumab for Atherosclerotic Disease) demonstrated that antibodies against interleukin-1β may decrease recurrent cardiovascular events in secondary prevention, various anti-inflammatory medications used for rheumatic conditions and new monoclonal antibody therapeutics have undergone rigorous evaluation. These data build towards a paradigm shift in secondary ASCVD prevention, underscoring the value of targeting multiple biological pathways in the management of both lipid levels and systemic inflammation. Evolving knowledge of the immune system, and the gut microbiota may result in opportunities for modifying previously unrecognized sources of residual inflammatory risk. This review provides an overview of novel therapeutic targets for ASCVD and emerging treatments with a focus on mechanisms, efficacy, and safety.
SARS-CoV-2 spike variants differ in their allosteric responses to linoleic acid
Authors: Oliveira A Sofia F , Shoemark Deborah K , Davidson Andrew D , Berger Imre , Schaffitzel Christiane , Mulholland Adrian J 
Published: October 2023

Abstract
The SARS-CoV-2 spike protein contains a functionally important fatty acid (FA) binding site, which is also found in some other coronaviruses, e.g. SARS-CoV and MERS-CoV. The occupancy of the FA site by linoleic acid (LA) reduces infectivity by ‘locking’ the spike in a less infectious conformation. Here, we use dynamical-nonequilibrium molecular dynamics (D-NEMD) simulations to compare the allosteric responses of spike variants to LA removal. D-NEMD simulations show that the FA site is coupled to other functional regions of the protein, e.g. the receptor-binding motif (RBM), N-terminal domain (NTD), furin cleavage site, and regions surrounding the fusion peptide. D-NEMD simulations also identify the allosteric networks connecting the FA site to these functional regions. The comparison between the wild-type spike and four variants (Alpha, Delta, Delta plus, and Omicron BA.1) shows that the variants differ significantly in their responses to LA removal. The allosteric connections to the FA site on Alpha are generally similar to those on the wild-type protein, with the exception of the RBM and the S71–R78 region, which show a weaker link to the FA site. In contrast, Omicron is the most different variant, exhibiting significant differences in the RBM, NTD, V622–L629, and furin cleavage site. These differences in the allosteric modulation may be of functional relevance, potentially affecting transmissibility and virulence. Experimental comparison of the effects of LA on SARS-CoV-2 variants, including emerging variants, is warranted.
Systematic literature review and meta-analysis of HER2 amplification, overexpression, and positivity in colorectal cancer
Authors: Singh Harshabad , Kang Ashley , Bloudek Lisa , Hsu Ling-I , Corinna Palanca-Wessels Maria , Stecher Michael , Siadak Muriel , Ng Kimmie 
Published: October 2023

Abstract

Background
Colorectal cancer (CRC) is the second most common cause of cancer death globally. Recent clinical trials suggest an emerging role for HER2 as a potential clinically relevant biomarker in CRC. Testing for HER2 in CRC is not standard practice; consequently, the prevalence of HER2 positivity (HER2+) in patients with CRC remains uncertain.

Methods
A systematic literature review and meta-analysis were conducted to generate estimates of proportions of patients with CRC with HER2 overexpression or HER2 amplification and HER2+ (either overexpression or amplification), overall and in patients with rat sarcoma virus (RAS) wild-type cancer. HER2+ was defined as 1) immunohistochemistry with a score of 3+, 2) immunohistochemistry with a score of 2+ and in situ hybridization+, or 3) next-generation sequencing positive.

Results
Of 224 studies identified with information on HER2 in CRC, 52 studies used a US Food and Drug Administration–approved assay and were selected for further analysis. Estimated HER2+ rate was 4.1% (95% confidence interval [CI] = 3.4% to 5.0%) overall (n = 17 589). HER2+ rates were statistically higher in RAS wild-type (6.1%, 95% CI = 5.4% to 6.9%) vs RAS mutant CRC (1.1%, 95% CI = 0.3% to 4.4%; P &lt; .0001). Despite limited clinical information, we confirmed enrichment of HER2+ CRC in patients with microsatellite stable and left-sided CRC.

Conclusion
This meta-analysis provides an estimate of HER2+ CRC and confirms enrichment of HER2 in microsatellite stable, left-sided, RAS wild-type CRC tumors. Our work is important given the recently described clinical efficacy of HER2-targeted therapies in HER2+ CRC and informs strategies for incorporation of HER2 testing into standard of care.
Effect of aerobic exercise on erectile function: systematic review and meta-analysis of randomized controlled trials
Authors: Khera Mohit , Bhattacharyya Samir , Miller Larry E 
Published: October 2023

Abstract

Background
The health benefits of regular aerobic exercise are well established, although there is limited high-quality evidence regarding its impact on erectile function.

Aim
To determine the effect of aerobic exercise on erectile function in men and to identify factors that may influence this effect.

Methods
This systematic review and meta-analysis included randomized controlled trials that evaluated the effects of aerobic exercise on erectile function via the Erectile Function domain of the International Index of Erectile Function (IIEF-EF). The mean difference in IIEF-EF scores between the aerobic exercise and nonexercising control groups was estimated by a random-effects meta-analysis. Meta-regression was used to evaluate the association of moderator variables on meta-analysis results.

Outcomes
The IIEF-EF score is reported on a 6-30 scale, with higher values indicating better erectile function.

Results
Among 11 randomized controlled trials included in the analysis, aerobic exercise resulted in statistically significant improvements in IIEF-EF scores as compared with controls, with a mean difference of 2.8 points (95% CI, 1.7-3.9; P &lt; .001) and moderate heterogeneity among studies (I2 = 53%). The effect of aerobic exercise on erectile function was greater in men with lower baseline IIEF-EF scores, with improvements of 2.3, 3.3, and 4.9 points for mild, moderate, and severe erectile dysfunction, respectively (P = .02). The meta-analysis results were not influenced by publication bias or individual study effects.

Clinical Implications
Health care providers should consider recommending regular aerobic exercise as a low-risk nonpharmacologic therapy for men experiencing erectile difficulties.

Strengths and Limitations
The primary strength of this review was the generation of level 1 evidence on a topic of general interest regarding sexual health in men. However, the included studies evaluated diverse groups, which may complicate data interpretation for specific segments of the population.

Conclusion
Regular aerobic exercise can improve the erectile function of men, particularly those with lower baseline IIEF-EF scores.
The battle plans in the 17th century on the example of the ‘ordres de bataille’ album by Eric Dahlbergh. Research model proposal
Authors: Balcerek Mariusz 
Published: October 2023

AbstractThe article’s purpose is to present an original method of analysis of battle plans (orders of battle, battle orders, battle patterns, and battle settings) from the 17th century. We analysed 253 patterns from Eric Dahlbergh’s Album, which was a gift for King Charles XI of Sweden. In this text, we will take a look at the settings presented in Dahlbergh’s album. We hope that it will allow us to learn about the development process of the 17th-century arrays. What was the typical 17th-century order of battle like? Was it symmetrical or asymmetrical? How many throws and lines did it consist of? What was the ratio of the width to the depth of the army? Was the pattern composed of compact or linear elements? How did the formations (cavalry and infantry) stack up against each other? What was the frequency of intervals and higher tactical units? Thanks to the developed method, we obtained data for many patterns for the first time in history. They made it possible to characterize the patterns accurately and determine the time they changed. It is of paramount importance for the study of the European military in the early modern period.
Acidic extracellular pH drives accumulation of N1-acetylspermidine and recruitment of protumor neutrophils
Authors: Kato Miki , Maeda Keisuke , Nakahara Ryuichi , Hirose Haruka , Kondo Ayano , Aki Sho , Sugaya Maki , Hibino Sana , Nishida Miyuki , Hasegawa Manami , Morita Hinano , Ando Ritsuko , Tsuchida Rika , Yoshida Minoru , Kodama Tatsuhiko , Yanai Hideyuki , Shimamura Teppei , Osawa Tsuyoshi 
Published: October 2023

Abstract
An acidic tumor microenvironment plays a critical role in tumor progression. However, understanding of metabolic reprogramming of tumors in response to acidic extracellular pH has remained elusive. Using comprehensive metabolomic analyses, we demonstrated that acidic extracellular pH (pH 6.8) leads to the accumulation of N1-acetylspermidine, a protumor metabolite, through up-regulation of the expression of spermidine/spermine acetyltransferase 1 (SAT1). Inhibition of SAT1 expression suppressed the accumulation of intra- and extracellular N1-acetylspermidine at acidic pH. Conversely, overexpression of SAT1 increased intra- and extracellular N1-acetylspermidine levels, supporting the proposal that SAT1 is responsible for accumulation of N1-acetylspermidine. While inhibition of SAT1 expression only had a minor effect on cancer cell growth in vitro, SAT1 knockdown significantly decreased tumor growth in vivo, supporting a contribution of the SAT1-N1-acetylspermidine axis to protumor immunity. Immune cell profiling revealed that inhibition of SAT1 expression decreased neutrophil recruitment to the tumor, resulting in impaired angiogenesis and tumor growth. We showed that antineutrophil-neutralizing antibodies suppressed growth in control tumors to a similar extent to that seen in SAT1 knockdown tumors in vivo. Further, a SAT1 signature was found to be correlated with poor patient prognosis. Our findings demonstrate that extracellular acidity stimulates recruitment of protumor neutrophils via the SAT1-N1-acetylspermidine axis, which may represent a metabolic target for antitumor immune therapy.
Progress in the application of molecular imaging in psychiatric disorders
Authors: Tan Jia , Zhang Guangying , Hao Jiaqi , Cai Huawei , Wu Dingping , Su Zhuoxiao , Liu Beibei , Wu Min 
Published: October 2023

Abstract
Psychiatric disorders have always attracted a lot of attention from researchers due to the difficulties in their diagnoses and treatments. Molecular imaging, as an emerging technology, has played an important role in the researchers of various diseases. In recent years, molecular imaging techniques including magnetic resonance spectroscopy, nuclear medicine imaging, and fluorescence imaging have been widely used in the study of psychiatric disorders. This review will briefly summarize the progression of molecular imaging in psychiatric disorders.
National Legislative Favorability and Insurance Coverage for Adult and Adolescent Gender-Affirming Surgery
Authors: LaValley Myles N. , Diaddigo Sarah E. , Asadourian Paul A. , Feuer Grant B. , Warner Paige E. , Rohde Christine H. 
Published: October 2023

Background:
Despite established medical necessity, laws prohibiting coverage discrimination, and increasing numbers of transgender and gender-diverse patients seeking gender-affirming surgery (GAS), cost and restrictive insurance policies continue to be the most common barriers. As recent legislation places further restrictions on GAS, this study aimed to provide an updated review of insurance policies and assess the relationship between legislative favorability and coverage.

Methods:
Insurance policies of groups representing 80% market coverage in each state were collected for gender-affirming chest, genital, and facial surgery. Policies were categorized based on previously published methodologies: never-covered, case-by-case, and preauthorization. The relationship between established scores of legislative favorability and policy coverage in each state was analyzed and compared across regions.

Results:
Of the 316 analyzed policies, coverage was preauthorized most often for genital (94.0%), masculinizing top (93%), feminizing top (74%), and facial reconstruction (24%). Higher legislative scores in the Northeast and West, and individual states were predictive of increased genital, facial, and all forms of adolescent GAS, but were not correlated to chest GAS.

Conclusions:
Compared with previous studies, our findings suggest that there is a growing acceptance of GAS as medically necessary. However, the correlation between legislative scores and genital, face, and adolescent GAS coverage may suggest increased reliance on sociopolitical factors for access in the absence of comprehensive medical guidelines, which are more established for chest reconstruction. Significantly higher coverage of masculinizing versus feminizing chest surgery suggests additional burden of proof for GAS with a cosmetic overlap.
Transconjunctival Fat Repositioning Using Barbed Sutures
Authors: Han Jungkyu , Han Seungkyu 
Published: October 2023

Summary:
Transconjunctival orbital fat repositioning is a surgical technique that resolves protruding orbital fat and sunken tear troughs through a single procedure. The procedure involves incision of the conjunctiva and dissection of the tear trough and orbicularis retaining ligaments, followed by repositioning of the sufficiently released orbital fat as a pedicle. Various techniques have been used to fixate the repositioned fat, including direct suturing of the fat to the target area (internal fixation) and suturing the repositioned fat pedicle and pulling out the suture toward the lower eyelid skin (external fixation). There are technical challenges attributable to both techniques, including a narrow operative field of view (internal fixation) and a high likelihood of relapse because the fat is not sutured directly to the tear trough area (external fixation). To overcome these disadvantages, the authors present a novel technique comprising barbed sutures.
A Surgical Management Algorithm for Type 4 Parry-Romberg Syndrome
Authors: Gu Tianyi , Yu Panxi , Teng Li , Zhang Chao 
Published: October 2023

Background:
Type 4 Parry-Romberg syndrome (PRS) affects multiple facial esthetic units involving many tissue types, requiring both bone and soft tissue restoration and requiring different surgical procedures over a long period of time. To date, the timing and sequence of these operations remains controversial.

Methods:
A retrospective analysis was performed to introduce our surgical management algorithm for type 4 PRS and to evaluate its safety and efficacy according to long-term follow-up results.

Results:
Six Chinese patients (5 females and 1 male) fulfilled the inclusion criteria. The follow-up period ranged from 23 to 90 months (mean 51.83 mo). All patients were satisfied with the improvement in facial appearance after staged bone and soft tissue reconstruction. No major complications were reported except for 1 case of infection after Medpor implantation.

Conclusions:
For severe PRS, both bone and soft tissue reconstruction is recommended. Enlargement of the bony framework provides a good foundation for subsequent soft tissue restoration. Alloplastic implants in the maxilla can be problematic if the patient has undergone either a zygomatic or maxillary osteotomy. The anterolateral thigh adipofascial flap is a reliable choice for large soft tissue deficits in type 4 PRS. We hope that reporting our surgical management algorithm with long-term follow-up results will improve the personalized treatment of these patients.
Reconstruction of Nasal Tip Using “Seagull-shaped” Cavum Concha Cartilage Composite Scaffold
Authors: Gao Fu-Lei , Lu Bo-Lun , Zhang Liu-Cheng , Mao Xi-Yuan , Sun Xiao-Ming , Zhang Yu-Guang 
Published: October 2023

Background:
The nasal tip plays a crucial role both esthetically and functionally. The application of nasal tip grafts is an effective method for improving nasal tip form. Ear cartilage is a common choice for nasal tip grafts, but it still presents several challenges in clinical application that need to be addressed. This study aims to address the issues associated with the use of ear cartilage in clinical rhinoplasty applications through the development of a novel septal extension graft using ear cartilage for nasal tip reconstruction.

Methods:
From May 2018 to April 2022, a total of 132 cases of nasal tip reconstruction surgeries were performed using a seagull-shaped nasal septum extension graft, constructed with bilateral cavum concha cartilage. Among these cases, 25 patients had previously undergone rhinoplasty using silicone implant, 7 patients had undergone augmentation rhinoplasty using expanded polytetrafluoroethylene, whereas the rest were primary rhinoplasty cases. All patients were followed up for a period ranging from 3 months to 4 years postoperatively, with photographs taken to assess the nasal tip morphology.

Results:
In this study, all patients exhibited good healing of the incisions made at the posterior aspect of the auricular concha, with no occurrences of hematoma and inconspicuous scarring. In 116 cases, significant improvement in nasal appearance and a realistic nasal tip form were achieved postoperatively, yielding satisfactory outcomes. Only 16 patients experienced minor issues with nasal tip morphology, which were subsequently improved through further surgical procedures.

Conclusion:
This study reports a surgical technique for nasal tip refinement using bilaterally harvested cavum concha cartilage to construct a seagull-shaped nasal septal extension graft. The procedure has achieved satisfactory outcomes, and its application is worth extending to clinical practice.
Outcomes of Endonasal Dacryocystorhinostomy Performed for Functional Nasolacrimal Obstruction With Delay on Dacryoscintigraphy
Authors: Hodgson Kevin , Hussain Ahsen 
Published: October 2023

Purpose:
To report the demographics and outcomes of endonasal dacryocystorhinostomy (DCR) following dacryoscintigraphy (DSG) performed for a series of patients with functional epiphora.

Methods:
Case series of endonasal DCR outcomes in patients with symptomatic epiphora with no evidence of lacrimal hypersecretion or lacrimal pump failure, minimal regurgitation noted on syringing, and DSG-confirmed delayed drainage. A successful outcome was defined as 80% subjective improvement or resolution of tearing on the operated side. Patient charts, DSG results, and operative records were examined, and data were collected. Relevant literature was reviewed and discussed.

Results:
The case series included 15 eyes of 10 patients. The mean age was 61.7 years at the time of surgery. Most cases (n=13) had post-sac obstruction, retention, or delay. One patient had pre and post-sac retention. A total of 12 cases had success after endonasal DCR, and 3 cases had failure. Follow-up for all operated patients was over 6 months. There were no reported complications by the surgeon or patients.

Conclusions:
Patients with functional epiphora confirmed by DSG seem to have a high success rate after endonasal DCR. In patients with symptomatic epiphora with subjective patency on syringing, the use of DSG in decision-making and outcome prediction may be supported. Further studies, including clinic-based tests, to demonstrate functional obstruction are warranted.
A decrease in the age of respired carbon from the terrestrial biosphere and increase in the asymmetry of its distribution
Authors: Sierra Carlos A. , Quetin Gregory R. , Metzler Holger , Müller Markus 
Published: October 2023

We provide here a model-based estimate of the transit time of carbon through the terrestrial biosphere, since the time of carbon uptake through photosynthesis until its release through respiration. We explored the consequences of increasing productivity versus increasing respiration rates on the transit time distribution and found that while higher respiration rates induced by higher temperature increase the transit time because older carbon is respired, increases in productivity cause a decline in transit times because more young carbon is available to supply increased metabolism. The combined effect of increases in temperature and productivity results in a decrease in transit times, with the productivity effect dominating over the respiration effect. By using an ensemble of simulation trajectories from the Carbon Data Model Framework (CARDAMOM), we obtained time-dependent transit time distributions incorporating the twentieth century global change. In these simulations, transit time declined over the twentieth century, suggesting an increased productivity effect that augmented the amount of respired young carbon, but also increasing the release of old carbon from high latitudes. The transit time distribution of carbon becomes more asymmetric over time, with more carbon transiting faster through tropical and temperate regions, and older carbon being respired from high latitude regions.
This article is part of the Theo Murphy meeting issue ‘Radiocarbon in the Anthropocene’.
Ecosystem and soil respiration radiocarbon detects old carbon release as a fingerprint of warming and permafrost destabilization with climate change
Authors: Schuur Edward A. G. , Hicks Pries Caitlin , Mauritz Marguerite , Pegoraro Elaine , Rodenhizer Heidi , See Craig , Ebert Chris 
Published: October 2023

The permafrost region has accumulated organic carbon in cold and waterlogged soils over thousands of years and now contains three times as much carbon as the atmosphere. Global warming is degrading permafrost with the potential to accelerate climate change as increased microbial decomposition releases soil carbon as greenhouse gases. A 19-year time series of soil and ecosystem respiration radiocarbon from Alaska provides long-term insight into changing permafrost soil carbon dynamics in a warmer world. Nine per cent of ecosystem respiration and 23% of soil respiration observations had radiocarbon values more than 50‰ lower than the atmospheric value. Furthermore, the overall trend of ecosystem and soil respiration radiocarbon values through time decreased more than atmospheric radiocarbon values did, indicating that old carbon degradation was enhanced. Boosted regression tree analyses showed that temperature and moisture environmental variables had the largest relative influence on lower radiocarbon values. This suggested that old carbon degradation was controlled by warming/permafrost thaw and soil drying together, as waterlogged soil conditions could protect soil carbon from microbial decomposition even when thawed. Overall, changing conditions increasingly favoured the release of old carbon, which is a definitive fingerprint of an accelerating feedback to climate change as a consequence of warming and permafrost destabilization.
This article is part of the Theo Murphy meeting issue ‘Radiocarbon in the Anthropocene’.