bluuebunny/crossref_metadata_2025 huggingface dataset:
Divergent effects of climatic factors on termite body size: alate versus worker castes
Authors: Lin Wen-Jun , Chiu Chun-I , Li Hou-Feng
Published: October 2024

Body size is an important functional trait to animals. Caste division of eusocial insects can exert a profound influence on their interactions with environment. We investigate the intra-specific variation of body size between caste within Odontotermes formosanus (Shiraki) (Blattodea: Termitidae), the most common and widely distributed termite species in Taiwan Island. By utilizing specimens from the NCHU Termite Collection and WorldClim data, we describe the body size distribution pattern of O. formosanus on two castes, worker and alate, and relationship with climatic factors is examined. The body size of workers is positively correlated with latitude and elevation. The body size of alates does not correlate with latitude but is positively correlated with elevation. Temperature factors negatively affect the body size of both castes. Precipitation has a positive effect on the body size of alates and no effect on workers. Additionally, humidity and temperature fluctuations over time have divergent effects on the body size of alates and workers. The results provide evidence of trait evolution decoupling at the intraspecific level, which may be shaped by climatic factors.
Clinical impact of multiple pectus bars on surgical outcomes following pectus excavatum repair
Authors: Oka Naoyuki , Masai Kyohei , Okubo Yu , Kaseda Kaoru , Hishida Tomoyuki , Asakura Keisuke
Published: October 2024

OBJECTIVES

The Nuss procedure, a minimally invasive surgery for pectus excavatum, has undergone various improvements. However, the impact of using multiple bars on thoracic shape changes and surgical outcomes remains unclear.

METHODS

We retrospectively evaluated patients who underwent the Nuss procedure for pectus excavatum between August 2014 and September 2021. We divided the patients into two groups based on the number of bars placed and identified differences in surgical outcomes and morphological characteristics.

RESULTS

A total of 225 patients were evaluated, of whom 132 were classified into the ≤2 bar group (using 1 or 2 bars) and 93 into the ≥3 bar group (using 3 or more bars). There was no difference in the preoperative Haller index (median [interquartile range], 4.59 [3.67–6.16] vs 4.67 [4.12–6.14], p = 0.227), and asymmetric excavatum was more frequently observed in the ≥3 bar group (81% vs 51%, p < 0.001). The preoperative sternal torsion angle was larger in the ≥3 bar group, but no difference was found between the two groups postoperatively. The incidence of postoperative complications (≥grade 3) was comparable between groups (10% vs 17%, p = 0.105); however, postoperative pleurisy was more frequently observed in the ≥3 bar group (12% vs 4%, p = 0.021). In univariable and multivariable analyses, ≥3 bar placement was the only risk factor for postoperative pleurisy.

CONCLUSIONS

The placement of multiple bars (≥3 bars) is useful for the correction of asymmetric pectus excavatum, but attention should be paid to the potential risk of postoperative pleurisy.
Nasal Mucosal Cytokines as Potential Biomarkers for Assessing Disease Severity and Class of Pathogen in Children With Community-Acquired Pneumonia
Authors: Sayegh Rouba , Tang Li , Yun Ki Wook , Xu Zhaohui , Marzec Sarah A , El-Assal Osama , Leber Amy L , Everhart Kathy , Mertz Sara , Desai Ankita , Cohen Daniel M , Alter Sherman J , Ambroggio Lilliam , Florin Todd A , Keaton Meghan , Shah Samir S , Ruddy Richard M , Wallihan Rebecca , Mejias Asuncion , Ramilo Octavio
Published: October 2024

Background

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in children. Assessing disease severity and etiology remains challenging in the clinical setting. The objective of this study was to identify mucosal biomarkers that could potentially assist with patient classification.

Methods

We analyzed mucosal concentrations of cytokines in nasopharyngeal samples obtained from a convenience sample of 182 children with CAP and 26 matched healthy controls. Pathogens were identified by cultures and molecular assays. Severe disease was defined by hospital stay ≥3 days and/or pediatric intensive care unit admission. Data were analyzed according to identified pathogens and disease severity.

Results

Children with CAP and detected atypical bacteria had significantly higher concentrations of monocyte chemotactic protein 2 (MCP-2), interferon gamma (IFN-γ), and CXCL10, among others, compared with those with typical bacteria. Children with influenza virus had significantly higher concentrations of MCP-2, CXCL10, CXCL11, CX3CL1, and IFN-γ than those with typical bacteria. Additionally, children with severe CAP had significantly higher concentrations of CCL23 than children with mild/moderate disease, irrespective of the pathogen(s) identified.

Conclusions

We identified differences in mucosal concentrations of inflammatory and antiviral cytokines in children with CAP according to disease severity and detected pathogens. Mucosal biomarkers represent a promising approach to help assess disease severity and etiology.
Demographic history of Platypus quercivorus (Coleoptera: Curculionidae), a beetle causing mass mortality of oak trees, in eastern Japan
Authors: Kobayashi Takuya , Ueda Akira , Taki Hisatomo , Aizawa Mineaki , Ito Masaaki , Nakamura Katsunori , Isono Masahiro , Wada Hisayuki , Uchida Yoko , Tokuda Sawako , Shoda-Kagaya Etsuko , Ozaki Kenichi
Published: October 2024

In recent years, Japanese oak wilt causing mass mortality of oak trees has exhibited a significant geographical expansion. Understanding the formation history of current local populations of Platypus quercivorus Murayama, a vector of Japanese oak wilt, is important foundational knowledge for effectively preventing forest damage. In this study, we used genome-wide single nucleotide polymorphism data to infer the population genetic structure and historical demography of P. quercivorus populations in eastern Japan, where Japanese oak wilt is rapidly expanding. We found at least 3 distinct genetic groups, each of which caused Japanese oak wilt in different areas. The supported scenario suggests that 1 of 2 genetic groups in the northeast first diverged from the ancestral population, then the other group diverged from the southwestern population, followed by gene flow between the 2 groups. Recent admixtures of the 2 northeastern groups were identified at certain sites. The geographic genetic structure of the populations suggested that each genetic group experienced recent range expansion. Although genetically independent populations had caused oak tree mass mortality in their original distribution range, our results support the hypothesis that the recent geographic expansion of Japanese oak wilt outbreaks is attributed to the range expansion of these P. quercivorus groups.
Intracellular methylglyoxal accumulation in classically activated mouse macrophages is mediated by HIF-1α
Authors: Prantner Daniel , Vogel Stefanie N
Published: October 2024

Approximately one million cases of sepsis in the United States occur annually. The early phase of sepsis features dramatic changes in host metabolism and inflammation. While examining the effects of metabolic pathways on inflammation, we discovered that the highly reactive glycolytic metabolite, methylglyoxal (MG), accumulates intracellularly during classical activation of macrophages. Herein, we explored the role of glycolysis and the master regulator of glycolysis, Hypoxia-Inducing Factor-1α (HIF-1α), in inflammation and MG accumulation in mouse and human macrophages. To determine how HIF-1α regulates the inflammatory response of macrophages, we correlated HIF-1α stabilization with proinflammatory gene expression and MG-adduct accumulation in WT vs HIF1a-deficient macrophages treated with LPS or LPS + IFN-γ. A nearly complete loss of HIF-1α protein expression in response to the hypoxia mimetic, cobalt chloride, confirmed the phenotype of the HIF1a-deficient macrophages. Moreover, absence of HIF-1α was also associated with decreased MG accumulation. Increasing the glucose concentration in cultured macrophages was sufficient to cause accumulation of endogenous MG-adducts which correlated with increased Tnf and Il1b expression during classical activation. The use of the MG antagonist, aminoguanidine, led to a significant decrease in Tnf and Il1b expression in both mouse macrophages and the THP-1 human macrophage cell line. Although off-target effects cannot be ruled out, these results are consistent with the possibility that MG regulates cytokine expression in classically activated macrophages. Collectively, this work suggests that HIF-1α stabilization is upstream of MG accumulation and that targeting the activity of HIF-1α in macrophages may be therapeutic during sepsis by limiting endogenous MG accumulation.
FemTech: empowering reproductive rights or FEM-TRAP for surveillance?
Authors: Hofmann Dylan
Published: October 2024

The emergence of FemTech technologies promises to revolutionize women’s health and reproductive rights but conceals an insidious trap of surveillance and control in the hands of private and state actors. This article examines the extent to which FemTech technologies, under the guise of empowerment, enable private actors to play a leading role in managing reproductive rights, replacing largely inactive States in this crucial function. The analysis shows how private FemTech companies are becoming critical players in implementing and defending these rights, often in response to the inaction or inadequacies of States. The article approaches the FemTech phenomenon from several angles, including the promises of empowerment, concerns about surveillance and control, and the ambivalent roles of private actors as implementers and defenders of reproductive rights. This structure makes it possible to offer a critical analysis of the legal, societal, and ethical implications of FemTech, highlighting the tensions between the promises of empowerment and the risks of surveillance and control.
Tussles with mussels: mytiloidean phylogeny revisited (Bivalvia: Pteriomorphia)
Authors: Tan Koh Siang , Tan Samuel Hui Ming
Published: October 2024

Our understanding of mytiloid phylogenetic relationships at the suprageneric level is still fragmentary despite previous attempts to make sense of their diverse but nevertheless characteristic body plan. The increasing availability of DNA barcode data for a wide range of mytilid taxa however now offers an unprecedented opportunity to examine their relatedness across the group. Here, we analysed publicly accessible sequences together with data from our own recent work on tropical shallow water marine, estuarine and freshwater species to construct molecular phylogenies involving key genera. Based on the tree topologies obtained from single- and multiple-gene analyses, a revised classification of the extant Mytiloidea is proposed, comprising two families Modiolidae and Mytilidae. This dichotomy is strongly supported in most trees generated. The Modiolidae encompasses mostly smooth-shelled taxa including Modiolinae, Bathymodiolinae, Limnoperninae and Xenostrobinae, together with Leiosolenus, Botula, Ciboticola, Lioberus, Jolya and Modiolula. Interestingly, the excavating Leiosolenus and freshwater Limnoperninae formed a group that is sister to the rest of the modiolid taxa. In contrast, the Mytilidae is a more varied group consisting of a wider range of taxa, amongst which Lithophaga and Dacrydium formed a sister clade to two well-supported clades, associated with the following genera: (1) Austromytilus, Brachidontes, Geukensia, Ischadium, Mytilaster, Mytilisepta, Perumytilus and Semimytilus; and (2) Arcuatula, Byssogerdius, Crenella, Gregariella, Musculus, Mytella, Mytilus, Parabrachidontes, Septifer and Trichomya. The first clade comprised exclusively of ribbed forms, whereas the second included both smooth and ribbed forms. Amygdalum, Aulacomya, Dacrydium, Lithophaga and Urumella were amongst several genera with unstable or uncertain affinities. In a cytochrome c oxidase subunit I tree, Amygdalum and Aulacomya formed a sister clade to the Modiolidae and Mytilidae. Shell morphology and anatomy are discussed in the light of these findings.
Genome wide clustering on integrated chromatin states and Micro-C contacts reveals chromatin interaction signatures
Authors: Sexton Corinne E , Victor Paul Sylvia , Barth Dylan , Han Mira V
Published: October 2024

We can now analyze 3D physical interactions of chromatin regions with chromatin conformation capture technologies, in addition to the 1D chromatin state annotations, but methods to integrate this information are lacking. We propose a method to integrate the chromatin state of interacting regions into a vector representation through the contact-weighted sum of chromatin states. Unsupervised clustering on integrated chromatin states and Micro-C contacts reveals common patterns of chromatin interaction signatures. This provides an integrated view of the complex dynamics of concurrent change occurring in chromatin state and in chromatin interaction, adding another layer of annotation beyond chromatin state or Hi-C contact separately.
Enhancing clinical decision-making: An externally validated machine learning model for predicting isocitrate dehydrogenase mutation in gliomas using radiomics from presurgical magnetic resonance imaging
Authors: Lost Jan , Ashraf Nader , Jekel Leon , von Reppert Marc , Tillmanns Niklas , Willms Klara , Merkaj Sara , Petersen Gabriel Cassinelli , Avesta Arman , Ramakrishnan Divya , Omuro Antonio , Nabavizadeh Ali , Bakas Spyridon , Bousabarah Khaled , Lin MingDe , Aneja Sanjay , Sabel Michael , Aboian Mariam
Published: October 2024

Background

Glioma, the most prevalent primary brain tumor, poses challenges in prognosis, particularly in the high-grade subclass, despite advanced treatments. The recent shift in tumor classification underscores the crucial role of isocitrate dehydrogenase (IDH) mutation status in the clinical care of glioma patients. However, conventional methods for determining IDH status, including biopsy, have limitations. Exploring the use of machine learning (ML) on magnetic resonance imaging to predict IDH mutation status shows promise but encounters challenges in generalizability and translation into clinical practice because most studies either use single institution or homogeneous datasets for model training and validation. Our study aims to bridge this gap by using multi-institution data for model validation.

Methods

This retrospective study utilizes data from large, annotated datasets for internal (377 cases from Yale New Haven Hospitals) and external validation (207 cases from facilities outside Yale New Haven Health). The 6-step research process includes image acquisition, semi-automated tumor segmentation, feature extraction, model building with feature selection, internal validation, and external validation. An extreme gradient boosting ML model predicted the IDH mutation status, confirmed by immunohistochemistry.

Results

The ML model demonstrated high performance, with an Area under the Curve (AUC), Accuracy, Sensitivity, and Specificity in internal validation of 0.862, 0.865, 0.885, and 0.713, and external validation of 0.835, 0.851, 0.850, and 0.847.

Conclusions

The ML model, built on a heterogeneous dataset, provided robust results in external validation for the prediction task, emphasizing its potential clinical utility. Future research should explore expanding its applicability and validation in diverse global healthcare settings.
Distinction of pseudoprogression from true progression in glioblastomas using machine learning based on multiparametric magnetic resonance imaging and O6-methylguanine-methyltransferase promoter methylation status
Authors: Yadav Virendra Kumar , Mohan Suyash , Agarwal Sumeet , de Godoy Laiz Laura , Rajan Archith , Nasrallah MacLean P , Bagley Stephen J , Brem Steven , Loevner Laurie A , Poptani Harish , Singh Anup , Chawla Sanjeev
Published: October 2024

Background

It is imperative to differentiate true progression (TP) from pseudoprogression (PsP) in glioblastomas (GBMs). We sought to investigate the potential of physiologically sensitive quantitative parameters derived from diffusion and perfusion magnetic resonance imaging (MRI), and molecular signature combined with machine learning in distinguishing TP from PsP in GBMs in the present study.

Methods

GBM patients (n = 93) exhibiting contrast-enhancing lesions within 6 months after completion of standard treatment underwent 3T MRI. Final data analyses were performed on 75 patients as O6-methylguanine-DNA-methyltransferase (MGMT) status was available only from these patients. Subsequently, patients were classified as TP (n = 55) or PsP (n = 20) based on histological features or mRANO criteria. Quantitative parameters were computed from contrast-enhancing regions of neoplasms. PsP datasets were artificially augmented to achieve balanced class distribution in 2 groups (TP and PsP). A random forest algorithm was applied to select the optimized features. The data were randomly split into training and testing subsets in an 8:2 ratio. To develop a robust prediction model in distinguishing TP from PsP, several machine-learning classifiers were employed. The cross-validation and receiver operating characteristic (ROC) curve analyses were performed to determine the diagnostic performance.

Results

The quadratic support vector machine was found to be the best classifier in distinguishing TP from PsP with a training accuracy of 91%, cross-validation accuracy of 86%, and testing accuracy of 85%. Additionally, ROC analysis revealed an accuracy of 85%, sensitivity of 70%, and specificity of 100%.

Conclusions

Machine learning using quantitative multiparametric MRI may be a promising approach to distinguishing TP from PsP in GBMs.
Is early-onset colorectal cancer an evolving pandemic? Real-world data from a tertiary cancer center
Authors: Angelakas Angelos , Christodoulou Thekla , Kamposioras Konstantinos , Barriuso Jorge , Braun Michael , Hasan Jurjees , Marti Kalena , Misra Vivek , Mullamitha Saifee , Saunders Mark , Cook Natalie
Published: October 2024

Background

Early onset Colorectal Cancer (EOCRC), defined as those diagnosed under the age of 50, has been increasing rapidly since 1970. UK data on EOCRC are currently limited and better understanding of the condition is needed.

Materials and Methods

A single-center retrospective study of patients with EOCRC treated over 9 years (2013-2021) at a large UK cancer center was performed. Clinicopathological features, risk factors, molecular drivers, treatment, and survival were analyzed.

Results

In total, 203 patients were included. A significant increase in cases was reported from 2018-2019 (n = 33) to 2020-2021 (n = 118). Sporadic EOCRC accounted for 70% of cases and left-sided tumors represented 70.9% (n = 144). Median duration of symptoms was 3 months, while 52.7% of the patients had de-novo metastatic disease. Progression-free survival after first-line chemotherapy was 6 months (95% CI, 4.85-7.15) and median overall survival (OS) was 38 months (95% CI, 32.86-43.14). In the advanced setting, left-sided primary tumors were associated with a median OS benefit of 14 months over right-sided primaries (28 vs 14 months, P = .009). Finally, primary tumor resection was associated with median OS benefit of 21 months compared with in situ tumors (38 vs 17 months, P < .001).

Conclusions

The incidence of EOCRC is increasing, and survival outcomes remain modest. Raising public awareness and lowering the age for colorectal cancer screening are directions that could improve EOCRC clinical outcomes. There is also a need for large prospective studies to improve the understanding of the nature of EOCRC and the best therapeutic approaches.
Calcium-dependent protein kinases 5 and 13 enhance salt tolerance in rice by directly activating OsMPK3/6 kinases
Authors: Su Shiqi , Jiang Yimin , Zhu Xiang , Yu Shibo , Wang Fuxiang , Xue Li , Cui Haitao
Published: October 2024

Mitogen-activated protein kinases (MAPKs/MPKs) are pivotal regulators in many stress-signaling pathways in plants. The dual phosphorylation of the TXY motif by MAP kinase kinases (MKKs) is essential for activating MAPKs. Here, we reveal a mechanism for MAPK activation that bypasses the need for MKKs. We identified rice (Oryza sativa) calcium-dependent protein kinase 5 (OsCPK5) and OsCPK13 as positive regulators in salt stress tolerance. These kinases are essential for the full activation of OsMPK3 and OsMPK6 in response to elevated sodium levels, with both OsMPK3 and OsMPK6 also acting as positive regulators in rice salt tolerance. Biochemical analysis demonstrated that OsCPK5/13 directly interact with and activate OsMPK3/6 by phosphorylating the TXY motif in vitro and in vivo. Additionally, we have discovered that OsCPK5/13 relocate from the cell membrane to the nucleus in response to salt stress. This process relies on their N-terminal myristoylation and a calcium-dependent phosphorylation event within the N-terminus. Our results elucidate a MAPK activation pathway in rice that is independent of traditional MKK-mediated phosphorylation, highlighting the crucial roles of OsCPK5 and OsCPK13 in directly phosphorylating and activating OsMPK3/6, which are important for rice tolerance to salt stress.
Management of blood loss in second-trimester abortion
Authors: Kaur Simranvir , Markwei Metabel Tori , Shaw Kate A.
Published: October 2024

Purpose of review

While major complications in second-trimester abortion are rare, blood loss and hemorrhage are among the most common and have the potential for high morbidity. Here, we review the current literature on risk factors, prevention, and treatment of blood loss in second-trimester abortion.

Recent findings

A comprehensive approach to hemorrhage during second-trimester abortions is essential. Understanding hemorrhage risk factors, prevention strategies, and treatment options makes second-trimester abortion safer. Some pharmacologic methods may both prevent and treat excessive blood loss. Mechanical methods are primarily used for treatment. Key risk factors include prior uterine scars, gestational duration, insufficient cervical preparation, high BMI, procedural inexperience, fetal demise, and halogenated anesthetics. Developing evidence-based protocols for and further research into hemorrhage related complications are crucial for improving safety in second-trimester abortion care.

Prevention of hemorrhage improves outcomes. However data are limited. For treatment, this includes using pharmacological interventions and mechanical methods. Identifying high-risk patients and implementing preprocedural optimization are proactive measures that aid in decreasing the occurrence and severity of blood loss and hemorrhage.
Patient navigation in reproductive healthcare
Authors: Schechter Melissa , Espey Eve , Krashin Jamie W.
Published: October 2024

Purpose of review

This review summarizes evidence about barriers to abortion care pre-Dobbs and post-Dobbs, inequities in abortion access, and approaches to improving access to abortion care with use of patient navigators.

Recent findings

The Dobbs decision and resulting state-level restrictions exacerbated economic, knowledge, and logistic barriers to abortion care. Abortion funds and emotional support are two main resources to help address these barriers; however, only with coordination can patients and clinics fully benefit from the resources. Patient navigation provides that coordination. Evidence shows it improves reproductive outcomes, is acceptable to patients and providers, and engages community health workers and community-based organizations.

Increasing legal restrictions and barriers to abortion care have motivated advocates to identify effective interventions to facilitate patient-centered and culturally competent care. Navigators have improved postpartum care by increasing attendance, education and helping coordinate overall care. They have improved referrals and access to abortion care in statewide programs.
Reconstruction of the Infraorbital Nerve Using Bilayered Artificial Nerve Conduits after Partial Maxillectomy
Authors: Oyama Aoi , Nakamura Ryota , Nakakawaji Mikumo , Nishikawa Daisuke , Beppu Shintaro , Maruyama Yoko , Okumura Seiko , Hanai Nobuhiro , Takanari Keisuke
Published: October 2024

Background:

Facial sensory nerves play vital roles in daily functions like self-protection, facial expressions, speaking, and eating. Severing the infraorbital nerve (ION) during partial maxillectomy via the Weber-Ferguson incision can lead to sensory disturbances. This study presents immediate ION reconstruction using artificial nerve conduits and its short-term outcomes.

Methods:

This retrospective study included three patients (mean age: 67.0 years) undergoing immediate ION reconstruction after partial maxillectomy via the Weber-Ferguson incision. Sensory recovery was evaluated using the Semmes-Weinstein and two-point discrimination (2PD) tests. A reference group of five patients who underwent total maxillectomy without ION reconstruction was also assessed.

Results:

No postoperative complications were observed during the 15.3-month follow-up. Sensory recovery varied among patients, with one achieving normal perception at 24 months, another showing diminished light touch at 13 months, and the third experiencing diminished protective sensation at 7 months postoperatively. In comparison, the reference group showed lower sensory recovery. Two patients showed improvements in 2PD test results at 24 and 13 months, whereas one showed no recovery at 7 months. No patients in the reference group showed improvement.

Conclusion:

Immediate ION reconstruction using artificial nerve conduits after partial maxillectomy appears feasible, as evidenced by acceptable sensory recovery in the short term.
Understanding Patient Satisfaction: A Comparative Analysis of Telemedicine versus In-person Encounters in Pediatric Plastic Surgery
Authors: Layon Sarah A. , Madueke Michael , Burns Heather R. , Parham Matthew J. , Wang Daniel S. , Olorunnipa Olushola
Published: October 2024

Background:

Telemedicine services experienced unprecedented growth during the coronavirus 2019 pandemic, offering patients remote access to care while minimizing exposures to possible infection. Our institution has one of the country’s largest pediatric plastic surgery divisions and serves both a prominent metro area and sprawling rural community. Given the increasing utilization of telemedicine across several surgical subspecialties, this study aims to evaluate patient satisfaction following pediatric plastic surgery telemedicine encounters.

Methods:

Press Ganey surveys were completed by parents or guardians of pediatric plastic surgery patients after in-person or telemedicine encounters with a single surgeon. Surveys were gathered from March 2020 to December 2022. Only 13 of the 25 survey questions were applicable to both in-person and telemedicine encounters and were included for analysis. Top box scores (the proportion of patients who selected the highest rating) were compared using Fisher exact test.

Results:

Completed surveys were available for both groups from June 2020 to November 2022. A total of 223 surveys met inclusion criteria; there were 159 in-person encounters and 64 telemedicine encounters. Telemedicine encounters consistently had top box scores comparable to, or greater than, in-person encounters for all 13 survey questions. Statistically significant differences were observed for ease of contacting the practice (P = 0.002) and scheduling appointments (P < 0.0001).

Conclusions:

Pediatric plastic surgery encounters completed via telemedicine demonstrate high patient satisfaction, exceeding in-person encounters for accessibility and convenience. Our study provides objective data about the patient experience and emphasizes the value of integrating telemedicine into pediatric plastic surgery practices.
Lipoprotein(a) is a highly atherogenic lipoprotein: pathophysiological basis and clinical implications
Authors: Björnson Elias , Adiels Martin , Borén Jan , Packard Chris J.
Published: October 2024

Purpose of review

Lipoprotein(a) has been identified as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis. However, as reviewed here, there is ongoing debate as to the key pathogenic features of Lp(a) particles and the degree of Lp(a) atherogenicity relative to low-density lipoprotein (LDL).

Recent findings

Genetic analyses have revealed that Lp(a) on a per-particle basis is markedly (about six-fold) more atherogenic than LDL. Oxidized phospholipids carried on Lp(a) have been found to have substantial pro-inflammatory properties triggering pathways that may contribute to atherogenesis. Whether the strength of association of Lp(a) with ASCVD risk is dependent on inflammatory status is a matter of current debate and is critical to implementing intervention strategies. Contradictory reports continue to appear, but most recent studies in large cohorts indicate that the relationship of Lp(a) to risk is independent of C-reactive protein level.

Lp(a) is a highly atherogenic lipoprotein and a viable target for intervention in a significant proportion of the general population. Better understanding the basis of its enhanced atherogenicity is important for risk assessment and interpreting intervention trials.
In remembrance: the life and legacy of George L. Bakris (1952–2024)
Authors: Sarafidis Pantelis A. , Tsioufis Kostas , Burnier Michel , Williams Bryan , Mancia Giuseppe , Weber Thomas , Stergiou George S. ,   the European Society of Hypertension and the International Society of Hypertension
Published: October 2024

George L. Bakris passed away on June 15, 2024 at the age of 72 years. This obituary aims at honoring his life and career by describing the stages in his personal and professional pathway, presenting some of his many remarkable accomplishments, and highlighting his exceptional clinical skills, mentorship, and friendship.
The Right Ventricular-Arterial Compliance Index: A Novel Hemodynamic Marker to Predict Right Heart Failure Following Left Ventricular Assist Device
Authors: Song Ning , Hungerford Sara L. , Barua Sumita , Kearney Katherine L. , Muthiah Kavitha , Hayward Christopher S. , Muller David W. M. , Adji Audrey I.
Published: October 2024

The development of right heart failure (RHF) in patients with advanced heart failure following left ventricular assist device (LVAD) implantation remains difficult to predict. We proposed a novel composite hemodynamic index—the right ventricular-arterial compliance index (RVACi), derived from pulmonary artery pulse pressure (PAPP), ejection time (ET), heart rate (HR), and cardiac output (CO), with

and expressed as mm Hg·s/L. We then conducted a retrospective, single-center analysis comparing the predictive value of RVACi for the development of RHF or unplanned right ventricular (RV) mechanical circulatory support following LVAD implantation against existing hemodynamic indices. One hundred patients were enrolled after screening 232 patients over a 10 year period, with 74 patients having complete hemodynamic data for RVACi calculation. There was good correlation between pulmonary arterial capacitance (R² = 0.48) and pulmonary vascular resistance (R² = 0.63) with RVACi, but not RV stroke work index or pulmonary artery pulsatility index. Reduced baseline RVACi (52 ± 23 vs. 92 ± 55 mm Hg·s/L; p = 0.02) was the strongest hemodynamic predictor of unplanned RV mechanical circulatory support requirement in patients following LVAD insertion. Composite pulsatile hemodynamic indices including RVACi may provide additional insight over existing hemodynamic indices for the prediction of RHF and need for RV mechanical circulatory support.
Quality of Life in People With HIV at the End of Life: Preliminary Results From the Last Gift Observational Cohort Study
Authors: Coler Brahm , Honerkamp Smith Gordon , Arora Anish K. , Wells Adam , Solso Stephanie , Dullano Cheryl , Concha-Garcia Susanna , Hill Eddie , Riggs Patricia K. , Korolkova Anastasia , Deiss Robert , Smith Davey , Sundermann Erin E. , Gianella Sara , Chaillon Antoine , Dubé Karine
Published: October 2024

Background:

As people living with HIV (PWH) age, they face new challenges that can have a negative impact on their quality of life (QOL) and mental health.

Setting:

This study enrolled PWH at the end of life (EOL) who were actively engaged in cure-related research in Southern California, United States. EOL was defined as having a prognosis of 6 months or less to live. We examined the relationship between QOL, mental health, and research participation.

Methods:

Structured assessments were used to collect comprehensive data on QOL and mental health.

Results:

From 2017 to 2023, 35 PWH in their final stages of life who were actively engaged in cure-related research were enrolled. Their median age was 62.7 years, and most were White or otherwise non-Hispanic/non-Latino (90.6%), and male (86.7%). Changes in QOL and the presence of neurologic and psychiatric conditions, with a focus on depression and anxiety, were the primary outcomes assessed in this study. Participants had stable QOL scores throughout the study. There was an inverse relationship between QOL and Beck Depression Inventory scores, with higher mean QOL scores being associated with lower mean Beck Depression Inventory scores (P < 0.001).

Conclusions:

QOL remained stable among PWH who participate in cure-related research at EOL. The inverse relationship between QOL and depressive symptoms suggests that participation in cure-related research may improve QOL or reduce depressive symptoms in this population. Future interventions should look into ways to improve the well-being of PWH at EOL through research and customized mental health interventions.
Surgical Reconstruction in Malignant Eyelid Tumors
Authors: Savur Fatma
Published: October 2024

Objective:

To report the histopathological subtypes of malignant eyelid tumors treated surgically in the author's clinic and to present the author's graft and flap preferences in the reconstruction of the eyelid defect after surgical excision.

Methods:

This retrospective study included 33 patients who underwent malignant eyelid tumor excision, followed by eyelid reconstruction. A frozen section was performed during surgery to assess surgical margins in all patients. Demographic characteristics, histological classification, localization, and size of the tumor, postoperative defect size, follow-up period, complications, and recurrence rate were recorded.

Results:

Of the patients with a mean age of 66.6 ± 15.3 (range: 23–94), 15 (45.5%) were females and 18 (54.5%) were males. The lower eyelid was the most commonly involved site in 27 (81.8%) patients. Basal cell carcinoma was the most frequently diagnosed type of malignant cancer in 81.8% (n = 27) of the cases. Among the tumor subtypes, nodular type basal cell carcinoma was the most frequently observed subtype in 10 (30.3%) patients. Wide excision with different flap and graft techniques was performed in 26 (78.8%) patients with defect sizes of 40% or larger. In the author's study, the most preferred flap technique for anterior lamella reconstruction was the Tenzel semicircular flap (30.3% n = 10). The most frequently preferred flap for posterior lamella reconstruction was the Hughes tarsoconjunctival flap (30.3% n = 10). There were no flap or graft failures in any of the author's cases.

Conclusion:

In the treatment of malignant eyelid tumors, different local flap and graft techniques selected according to the size of the defect have successful anatomical results in reconstructive surgery after frozen section controlled excision.
The Frequency of Presence of the Infraorbital Canal in the Maxillary Sinus and its Clinical Importance
Authors: Tekin Mustafa Said , Karaalioğlu Banu
Published: October 2024

Objective:

The infraorbital canal (IOC) houses critical structures like the infraorbital artery, vein, and nerve, and its atypical location within the maxillary sinus could pose risks during surgical procedures, making it crucial to understand its prevalence and distribution. The study aims to investigate the localization and frequency of the IOC within the maxillary sinus.

Methods:

This retrospective study analyzed computed tomography (CT) images from 1000 randomly selected patients (500 males, 500 females) aged 18 to 65 years who underwent paranasal region imaging at Istanbul Medipol University Medipol Mega University Hospital between 2015 and 2020. Exclusion criteria included major pathologies, prior surgeries, and poor image quality. The study focused on evaluating the localization of the IOC and its presence within the maxillary sinus, using coronal CT sections.

Results:

The IOC was found within the maxillary sinus in 8% of cases (44 males, 36 females). This variation was bilateral in 34 cases and unilateral in 46 cases, with no statistically significant relationship between sex and the occurrence or type of variation. The study’s findings align with previous research, which reported similar prevalence rates for this anatomical variation.

Conclusion:

The study confirms that the IOC is located within the maxillary sinus in a significant percentage of cases, emphasizing the importance of preoperative CT evaluation to prevent potential complications during maxillary sinus surgeries. These findings highlight the clinical relevance of considering individual anatomical differences in the localization of the IOC.
Paravertebral versus EPidural Analgesia in Minimally Invasive Esophageal ResectioN (PEPMEN)
Authors: Feenstra Minke L. , Kooij Cezanne D. , Eshuis Wietse J. , de Groot Eline M. , Hermanides Jeroen , Kingma B. Feike , Gisbertz Suzanne S. , Ruurda Jelle P. , Daams Freek , Marsman Marije , van den Bosch Oscar F.C. , ten Hoope Werner , Goense Lucas , Luyer Misha D.P. , Nieuwenhuijzen Grard A.P. , Scholten Harm J. , Buise Marc , van Det Marc J. , Kouwenhoven Ewout A. , van der Meer Franciscus , Frederix Geert W.J. , Hollmann Markus W. , Cheong Edward , van Berge Henegouwen Mark I. , van Hillegersberg Richard
Published: October 2024

Objective:

To compare quality of recovery in patients receiving epidural or paravertebral analgesia for minimally invasive esophagectomy (MIE).

Summary Background Data:

Paravertebral analgesia may be a promising alternative to epidural analgesia, avoiding potential side effects and improving postoperative recovery.

Methods:

This randomized controlled superiority trial was conducted across four Dutch centers with esophageal cancer patients scheduled for transthoracic MIE with intrathoracic anastomosis, randomizing patients to receive either epidural or paravertebral analgesia. The primary outcome was Quality of Recovery (QoR-40) on the third postoperative day (POD). Secondary outcomes included quality of life, postoperative pain, opioid consumption, inotropic/vasopressor medication use, hospital stay, complications, readmission, and mortality.

Results:

From December 2019 to February 2023, 192 patients were included: 94 received epidural and 98 paravertebral analgesia. QoR-40 score on POD3 was not different between groups (mean difference 3.7, 95%CI -2.3 to 9.7; P=0.268). Epidural patients had significant higher QoR-40 scores on POD1 and 2 (mean difference 7.7, 95%CI 2.3-13.1; P=0.018 and mean difference 7.3, 95%CI 1.9-12.7; P=0.020) and lower pain scores (median 1 versus 2; P=<0.001 and median 1 versus 2; P=0.033). More epidural patients required vasopressor medication on POD1 (38.3% versus 13.3%; P<0.001). Urinary catheters were removed earlier in the paravertebral group (median POD3 versus 4; P=<0.001). No significant differences were found in postoperative complications or hospital/Intensive Care Unit stay.

Conclusions:

This randomized controlled trial did not demonstrate superiority of paravertebral over epidural analgesia regarding quality of recovery on POD3 after MIE. Both techniques are effective and can be offered in clinical practice.
Culinary Medicine in the Registered Dietitian Nutritionist Education Pathway
Authors: Harris Stephanie R. , Barkoukis Hope D. , Burns Ann C. , Ricelli Olivia , McWhorter John Wesley , McManus Catherine R.
Published: October 2024

Although registered dietitian nutritionists (RDNs) are well-positioned to be impactful contributors to interprofessional culinary medicine (CM) teams, the absence of mandatory CM training in the RDN education pathway may significantly limit their potential positive impact. In this preliminary study, program directors of supervised practice programs express strong interest and acknowledgment of the value of CM education for RDNs but varied inclusion across programs. Considering CM’s rapid growth and the RDN’s role as a food and nutrition expert, creating mandatory knowledge and competency standards in CM to better prepare RDNs for future practice warrants consideration.
Diagnostic Value of Bereitschaftspotential in People With Functional Seizures
Authors: Dietze Christoph S. , van Waart-Houtman Dieke , Meppelink Anne Marthe , Bourez-Swart Mireille , van der Palen Job , Zijlmans Maeike , van der Salm Sandra M. A.
Published: October 2024

Purpose:

Bereitschaftspotential (BP) or readiness potential in people with functional movement disorders can aid diagnostic workup. We evaluated the diagnostic value of BP as an interictal EEG marker in people with functional seizures (FS).

Methods:

We recorded and analyzed BP interictal before intended movements in 17 adults with FS and 17 controls with alternative diagnoses. We evaluated the signals for the presence of BP, latency, amplitude, and early versus late BP.

Results:

Bereitschaftspotential was present in all except one person with FS. We found no significant differences in the latency and amplitude of BP between participants with FS and controls. The early BP showed the most significant variance in amplitude, latency, and presence.

Conclusions:

We found interictal typical BP values in participants with FS and variable semiology, while earlier research found interictal no BP in functional movement disorders. These findings do not support the use of BP as an interictal diagnostic tool for FS. Differences in early BP and focus on FS with pure motor semiology are starting points for further research evaluating potential interictal markers in people with FS.
Genomic characterization of Haemophilus influenzae harbouring an exogenous resistance gene
Authors: Tanaka Emi , Wajima Takeaki , Hirano Sonoe , Seyama Shoji , Nakaminami Hidemasa , Uchiya Kei-ichi
Published: October 2024

Introduction. Reports of β-lactamase-producing Haemophilus influenzae are increasing worldwide.

Aim. This study aimed to elucidate the molecular characteristics and evolution of β-lactamase-producing H. influenzae.

Methodology. A total of 159 clinical isolates were characterized using multi-locus sequence typing. Antimicrobial resistance genes and integrative and conjugative element (ICE) types were identified through PCR and DNA sequencing. The genetic structure of ICE was further investigated using whole-genome sequencing.

Results. Out of 159 clinical isolates, 20.8% (n=33) were β-lactamase producers. Thirteen sequence types (STs) were identified. ST 103, 155, 165 and 388 have been identified in previous studies, suggesting that strains with these STs tend to acquire the β-lactamase gene bla
TEM-1. Among β-lactamase producers, 66.7% (n=22) of bla
TEM-1 were located on ICE. The ICEs could be classified into two groups based on their sequence (types I and II). Among these strains, 2017-Y3 harboured a macrolide resistance gene, mef (A/E), in ICE. A comparative analysis of the ICE region of this strain and those from other countries suggested that each isolate was derived from ICE type I or II. These regions, including mef (A/E), were similar to those of Tn6822, which is commonly found in Streptococcus.

Conclusions. This study revealed several STs associated with the acquisition of β-lactamase genes on ICEs. Additionally, ICE evolution involved the acquisition of exogenous genes. The accumulation of resistance genes in ICE raises concerns regarding the emergence of multidrug-resistant H. influenzae.
Ligase-mediated programmable genomic integration (L-PGI): an efficient site-specific gene editing system that overcomes the limitations of reverse transcriptase-based editing systems
Authors: Nan Angela Xinyi , Chickering Michael , Bartolome Christopher , Shadija Neeta , Li Dan , Estes Brett , Stetina Jessica Von , Li Wei , Andresen Jason , Cochrane Jesse C , Bai Chen , Gatlin Jason , Wang Jie , Norouzi Davood , Kumar Sandeep , Dunyak Maike Thamsen , Chavez Leonard , Seth Anmol , Halperin Shakked , Finn Jonathan D , Xie Jenny
Published: October 2024

Since their discovery, CRISPR/Cas9 systems have been repurposed for programmable targeted genomic editing. This has led to unprecedented advancement of gene editing for therapeutic benefit. Initial uses of CRISPR/Cas9 were focused on gene disruption via DNA cleavage, but significant engineering led to systems for single base editing as well as insertion, deletion and manipulation of short stretches of genomic sequences using nicking Cas9 and RT-based methods. These technologies allowed safer and more precise editing but were limited to small corrections and showed significantly reduced efficiencies in nondividing cells, presenting difficulty for translation toin vivotherapies. To find an alternate editing strategy that could address these shortcomings, we revisited the mechanism of DNA nicking by nCas9. nCas9 nicking creates a free 5’ phosphate group and a 3’ hydroxyl group on the complementary strand of the target sequence. Under ordinary conditions in the cell these ends are re-joined by endogenously expressed ligases to repair DNA back to wild-type. If, however, a DNA fragment containing the desired edit were present, ligation of the nicked genomic DNA with the delivered fragment could result in gene editing. We demonstrate that optimization of each component and introduction of a chemically modified high affinity splinting DNA allows a variety of ligase-based edits, including longer edits not efficient with RT-based systems, at high efficiencies and fidelities that minimize genomic byproducts in both dividing and nondividing cells as well asin vivoin adult mice. Here we present the first therapeutically relevant ligation-based programmable gene editing technology, L-PGI.
Rapid Prototyping of 3D Microstructures: A Simplified Grayscale Lithography Encoding Method Using Blender
Authors: Borghi Fabrício Frizera , Bendimerad Mohammed , Chapon Marie-Ly , Petithory Tatiana , Vonna Laurent , Pieuchot Laurent
Published: October 2024

The democratization of fabrication equipment has spurred recent interest in maskless grayscale lithography for both 2D and 3D microfabrication. However, the design of suitable template images remains a challenge. This work presents a simplified method for encoding 3D objects into grayscale image files optimized for grayscale lithography. Leveraging the widely used, open-source 3D modeling software Blender, we developed a robust approach to convert geometric heights into grayscale levels and generate image files through top-view rendering. Our method accurately reproduced the overall shape of simple structures like stairs and ramps compared to the original designs. We extended this approach to complex 3D sinusoidal surfaces, achieving similar results. Given the increasing accessibility and user-friendliness of digital rendering tools, this study offers a promising strategy for rapid prototyping of initial designs with minimal effort.