bluuebunny/crossref_metadata_2025 huggingface dataset:
Online Portfolio Optimization with Risk Control
Authors: Yamim João Daniel Madureira , Borges Carlos Cristiano Hasenclever , Neto Raul Fonseca
Published: January 2022

Portfolio selection is undoubtedly one of the most challenging topics in the area of finance. Since Markowitz's initial contribution in 1952, portfolio allocation strategies have been intensely discussed in the literature. With the development of online optimization techniques, dynamic learning algorithms have proven to be an effective approach to building portfolios, although they do not assess the risk related to each investment decision.In this work, we compared the performance of the Online Gradient Descent (OGD) algorithm and a modification of the method, that takes into account risk metrics controlling for the Beta of the portfolio. In order to control for the Beta, each asset was modeled using the CAPM model and a time-varying Beta that follows a random walk. We compared both the traditional OGD algorithm and the OGD with Beta constraints with the Uniform Constant Rebalanced Portfolio and two different indexes for the Brazilian market, composed of small caps and the assets that belong to the Ibovespa index. Controlling the Beta proved to be an efficient strategy when the investor chooses an appropriate interval for the beta during bull markets or bear markets. Moreover, the time-varying beta was an efficient metric to force the desired correlation with the market and also to reduce the volatility of the portfolio during bear markets.
Refractive Errors and Concomitant Strabismus in Children and Adolescents: A Hospital Based Observational Study
Authors: Singh Anupam , Chawla Omna , Verma Rupal , Saxena Vartika , Kumari Ranjeeta , Patnaik Nisheeta , Kumar Barun , Kumawat Devesh
Published: January 2022

Purpose:

To study the different types of concomitant strabismus and associated refractive errors in children and adolescents.

Material & Methods:

In this observational study, 178 patients aged between 4-19 yrs with concomitant strabismus of ≥ 15 Prism Dioptre (PD) on prism bar cover test were included and examined by a strabismus expert for type and amount of deviation between July 2017 to June 2020 at a tertiary health care hospital in north India. Non-cycloplegic and cycloplegic refraction was performed by a trained optometrist. Glasses were prescribed to achieve the best corrected visual acuity (BCVA). Data collection was done using a predesigned and pretested questionnaire.

Results:

The mean age of the study population was 11.20 ± 5.49 years (Median: 10, range = 4-19 years) and 97 patients (55.5 %) were male and 81 (45.5%) were female. Seventy-five patients (42.13%) were esotropes, 87 (48.87%) were exotropes and 16 (8.99%) were in combined deviation group. Hypermetropia (83/140, 59.28%) was the most common type of refractive error among ametropes (140/178). Among the hypermetropes, 52 (62.7%) had esotropia and 25 (64.1%) of the myopes had exotropia. Further, 52 (69.3%) of the esotropes had hypermetropia but there was no such trend of error noticed among the exotropes (p value < 0.001, Chi-square test). There were 70 (39.32%) amblyopes in the study population, out of which 35 (50%) had esotropia (p value: 0.032, Chi-square test).

Conclusion:

Hypermetropia was the most common refractive error among the study population and hypermetropes were prone to have esotropia and vice-versa. Esotropia and hypermetropia were more common among amblyopes.
A Novel RAGE Modulator Induces Soluble RAGE to Reduce BACE1 Expression in Alzheimer's Disease
Authors: Baek Seung‐Hyun , Hong Suji , Kim Eunae , Park Sunyoung , Lee Minyoung , Park Jinsu , Cho Yoonsuk , Yoon Hyunjun , Kim Daeseung , Yun Youngkwang , Kim Youbin , Choi Yoonjung , Kang Keunsoo , Jung Sangyong , Kim Jun Pyo , Kim Eunha , Seo Sang Won , Jung Yong‐Keun , Jo Dong‐Gyu
Published: January 2025

β‐secretase (BACE1) is instrumental in amyloid‐β (Aβ) production, with overexpression noted in Alzheimer's disease (AD) neuropathology. The interaction of Aβ with the receptor for advanced glycation endproducts (RAGE) facilitates cerebral uptake of Aβ and exacerbates its neurotoxicity and neuroinflammation, further augmenting BACE1 expression. Given the limitations of previous BACE1 inhibition efforts, the study explores reducing BACE1 expression to mitigate AD pathology. The research reveals that the anticancer agent 6‐thioguanosine (6‐TG) markedly diminishes BACE1 expression without eliciting cytotoxicity while enhancing microglial phagocytic activity, and ameliorate cognitive impairments with reducing Aβ accumulation in AD mice. Leveraging advanced deep learning‐based tool for target identification, and corroborating with surface plasmon resonance assays, it is elucidated that 6‐TG directly interacts with RAGE, modulating BACE1 expression through the JAK2‐STAT1 pathway and elevating soluble RAGE (sRAGE) levels in the brain. The findings illuminate the therapeutic potential of 6‐TG in ameliorating AD manifestations and advocate for small molecule strategies to increase brain sRAGE levels, offering a strategic alternative to the challenges posed by the complexity of AD.
High‐Throughput Formation of Pre‐Vascularized hiPSC‐Derived Hepatobiliary Organoids on a Chip via Nonparenchymal Cell Grafting
Authors: Fan Han , Shang Jia , Li Junbo , Yang Bo , Zhou Ding , Jiang Shanqing , Fan Yuhang , Zhou Ying , Wang Yuwen , Liu Peidi , Li Changyong , Chen Zhishui , Chen Pu
Published: January 2025

Liver organoids have been increasingly adopted as a critical in vitro model to study liver development and diseases. However, the pre‐vascularization of liver organoids without affecting liver parenchymal specification remains a long‐lasting challenge, which is essential for their application in regenerative medicine. Here, the large‐scale formation of pre‐vascularized human hepatobiliary organoids (vhHBOs) is presented without affecting liver epithelial specification via a novel strategy, namely nonparenchymal cell grafting (NCG). Endothelial and mesenchymal cells are grafted to human hepatobiliary organoids (hHBOs) at the different liver epithelial differentiation stages without supplementing with nonparenchymal culture medium and growth factors. Endothelial grafting at the stage of hepatic maturation offers an optimal integration efficiency compared to the stage of hepatic specification. Additionally, grafting with mesenchymal proves crucial in endothelial invading and sprouting into the liver epithelial cells during the establishment of vhHBOs. Ectopic liver implants into mice further displayed integration of vhHBOs into mice vascular networks. Notably, transplanted vhHBOs self‐organized into native liver tissue like hepatic zone and bile ducts, indicating their potential to regenerate damaged hepatic and bile duct tissues. It is believed that nonparenchymal cell grafting will offer a novel technical route to form a high‐fidelity complex in vitro model for tissue engineering and regenerative medicine.
Engineered MSC‐sEVs as a Versatile Nanoplatform for Enhanced Osteoarthritis Treatment via Targeted Elimination of Senescent Chondrocytes and Maintenance of Cartilage Matrix Metabolic Homeostasis
Authors: Feng Kai , Liu Jiashuo , Gong Liangzhi , Ye Teng , Chen Zhengsheng , Wang Yang , Li Qing , Xie Xuetao
Published: January 2025

Chondrocyte senescence is an important pathogenic factor causing osteoarthritis (OA) progression through persistently producing pro‐inflammatory factors. Mesenchymal stem cells‐derived small extracellular vesicles (MSC‐sEVs) have shown anti‐inflammatory effects in OA models, while persistent existence of senescent chondrocytes still promotes cartilage destruction. Therefore, improving the targeted elimination ability on senescent chondrocytes is required to facilitate the translation of MSC‐sEVs in OA treatment. In this study, versatile engineered MSC‐sEVs are developed to targetedly clear senescent chondrocytes and maintain cartilage metabolic homeostasis. Specifically, MSC‐sEVs are loaded with siRNA mouse double minute 2 homologue (siMDM2) and modified with cartilage‐targeting peptide WYRGRL‐PEG2K‐DSPE (WPD), named WPD‐sEVssiMDM2. The results demonstrate versatile modification improves the cellular uptake of MSC‐sEVs in chondrocytes, and thus improves the antiaging effects. Importantly, multifunctional modification enhances cartilage penetration ability and extends joint retention time of MSC‐sEVs. In both post‐traumatic OA mice and naturally aged mice, WPD‐sEVssiMDM2 more effectively eliminates senescent chondrocytes and maintained matrix metabolic homeostasis. By using the P53 phosphorylation inhibitor, the essential role MDM2‐P53 pathway in the antiaging function of WPD‐sEVssiMDM2 on chondrocytes is verified. In ex vivo cultured human OA cartilage explants, it is confirmed that WPD‐sEVssiMDM2 alleviates senescent phenotype. Altogether, the findings suggest that WPD‐sEVssiMDM2 have promising translational potential for OA treatment.
Unipolar Barrier Photodetectors Based on Van Der Waals Heterostructure with Ultra‐High Light On/Off Ratio and Fast Speed
Authors: Wang Suofu , Wang Xiuxiu , Wang Wenhui , Han Tao , Li Feng , Shan Lei , Long Mingsheng
Published: January 2025

Unipolar barrier architecture is designed to enhance the photodetector's sensitivity by inducing highly asymmetrical barriers, a higher barrier for blocking majority carriers to depressing dark current, and a low minority carrier barrier without impeding the photocurrent flow through the channel. Depressed dark current without block photocurrent is highly desired for uncooled Long‐wave infrared (LWIR) photodetection, which can enhance the sensitivity of the photodetector. Here, an excellent unipolar barrier photodetector based on multi‐layer (ML) graphene (G) is developed, WSe2, and PtSe2 (G‐WSe2‐PtSe2) van der Waals (vdW) heterostructure, in which extremely low dark current of 1.61×10−13 A, a record high light on/off ≈109 are demonstrated at 0 V. Notably, the device exhibits ultrafast response speed with rise time τr = 699 ns and decay time τd = 452 ns and high‐power conversion efficiency (η) of 4.87%. The heterostructure demonstrates a broadband photoresponse from 365 nm to LWIR 10.6 µm at room temperature. Notably, the G‐WSe2‐PtSe2 nBn device demonstrates high photoresponsivity (R) of 1.8 AW−1 with 10.6 µm laser at 1 V bias in ambient air. This unipolar barrier device architecture offers an alternative way for highly sensitive free space communication.
Clinical impact of low fornix perfusion on devascularized whole stomach as a risk factor for anastomotic leakage after esophagectomy
Authors: Takahashi Keita , Yuda Masami , Ishikawa Yoshitaka , Masuda Takahiro , Kurogochi Takanori , Fukushima Naoko , Matsumoto Akira , Tsuboi Kazuto , Nishikawa Katsunori , Yano Fumiaki , Eto Ken
Published: January 2025

Backgrounds

We previously reported poor vascularity of narrow gastric tube evaluated by thermography was associated with anastomotic leakage (AL) after esophagectomy. Meanwhile, the association between the fornix low perfusion on devascularized whole stomach (DWS) and the incidence of AL remains unclear. Therefore, this study aimed to clarify the impact of the fornix low perfusion on DWS.

Methods

A total of 238 patients who underwent Mckeown esophagectomy with gastric tube reconstruction between 2008 and 2021 were analyzed. Patients were divided into non‐AL and AL groups and their clinical outcomes including vascular factors of DWS and gastric tube were compared. Additionally, the logistic regression analysis was conducted to detect the risk factors of AL.

Results

AL occurred in 31 patients (13.0%). Regarding vascular factors, avascular area temperature retain rate (Av‐TRr) on DWS, right gastroepiploic artery length rate and anastomotic viability index (AVI) on gastric tube were significantly smaller in the AL group than in the non‐AL group. In logistic regression model for AL, multivariate analysis showed that diabetes (Odds ratio [OR], 3.90; 95% confidence interval [CI], 1.32–11.60), hand‐sewn anastomosis (OR, 4.42;95% CI, 1.05–18.60), Av‐TRr on DWS<0.91 (OR, 4.67; 95% CI, 2.00–10.90), and AVI<0.64 (OR, 2.68; 95% CI, 1.12–6.39) were significant risk factors.

Conclusions

Fornix low perfusion on DWS was a risk factor of AL as well as low AVI on gastric conduit. Additionally, fornix low perfusion on DWS was correlated with low AVI on gastric conduit.
Novel Fluoroquinolones With Pinane Moiety: Synthesis and Antimicrobial Activity
Authors: Gilfanov Ilmir R. , Kolesnikova Alyona I. , Pavelyev Roman S. , Sudarikov Denis V. , Gribkov Pavel V. , Izmest'ev Evgeniy S. , Rubtsova Svetlana A. , Lisovskaya Svetlana A. , Babaeva Olga B. , Rakhmatullin Ilfat Z. , Davletshin Rustam R. , Klochkov Vladimir V. , Nikitina Liliya E. , Kayumov Airat R. , Trizna Elena Y.
Published: January 2025

Here, we report a synthesis of fluoroquinolones carrying a monoterpene moiety at the C7 position of aromatic structure. The minimal inhibitory concentrations of fluoroquinolone fused with trans‐3‐hydroxy‐cis‐myrtanylamine 18 against Staphylococcus aureus (MSSA isolates) were two‐ to eightfold lower compared to moxifloxacin, although fourfold higher against MRSA isolates. The fluoroquinolone fused with (−)‐nopylamine 16 was four‐ to eightfold less active on MSSA compared to moxifloxacin, while had similar activity on MRSA. Against biofilms, both 16 and 18 were four times more active than both moxifloxacin and ciprofloxacin. Both 16 and 18 induced the drop of membrane potential and in silico exhibited similar binding energies with DNA gyrase of S. aureus (ΔG −13.44 to −13.17 kcal/mol), suggesting dual mechanism of action (topoisomerase inhibition by the fluoroquinolone core and membrane damage by the monoterpene fragment). Thus, our data demonstrate the perspectives of monoterpenes fusion to an antibiotic moiety to obtain dual‐acting bipharmacophore antimicrobials with improved activity, including biofilm‐associated infections.
Shared Governance and ESG Rating: Evidence From Korea
Authors: Jo Hoje , Chun Hongmin , Song Hakjoon
Published: January 2025

This paper examines how shared governance structure affects firms' ESG rating using unique co‐CEO data in Korea for 2012–2019. We argue that coordination issues, interpersonal conflicts, and mutual monitoring of cosmetic ESG activities under the co‐CEO structure would decrease ESG ratings. Consistent with the premise, we find that co‐CEO firms disclose lower ESG ratings, especially social scores, than firms led by solo CEOs. However, Korean business group Co‐CEOs disclose higher ESG ratings due to reputation concerns, insurance benefits, and responsibility toward society. We further find that the negative association between co‐CEO structure and ESG rating is more pronounced in firms with low cash holding and high product market competition. We perform 2SLS estimation, PSM sample analyses, and entropy balancing approach to address possible endogeneity concerns along with self‐selection bias problems, and the results reinforce our main findings.
Impacts of City Life on Nutrition: Evidence From Resettlement Lotteries in China
Authors: Leng Ganxiao , Qiu Huanguang , Filipski Mateusz
Published: January 2025

Urban environments are thought to improve food security, by offering enhanced access to markets and income opportunities. Yet this idea is hard to test empirically due to an abundance of confounding factors and selection issues. This study leverages a resettlement program in China to provide the first quasi‐experimental estimate of city life on food consumption and nutrition among low‐income households. Lottery‐determined timing of resettlement enables causal inference. We base our empirics on a 3‐year panel and a range of difference‐in‐differences and matching methodologies. We find that those who were resettled to towns significantly increased both food consumption and diet variety, with increased intake of several macro‐ and micro‐nutrients. Diet quality mostly improved, but we also found signs of over‐consumption, notably of carbohydrates. Our evidence further suggests that our impacts are primarily due to improved market access. This stands in contrast to recent literature that finds little or no effect of living environments on food consumption. Instead, we reveal a significant impact of urban environments in shaping diets, bolstering the notion that supply‐side channels do matter in some contexts.
Cancer‐Associated Fibroblast‐Secreted Exosomes Regulate Macrophage Polarization in Pancreatic Cancer via the NOD1 Pathway
Authors: Yang Wenxin , Zheng Yuanyuan , Zhou Han , Liang Ruolong , Hu Chaofeng
Published: January 2025

Metastasis is a major cause of poor prognosis of pancreatic cancer. Exosomes (Exos) regulate cancer progression by modulating macrophage polarization. This study aimed to investigate the effects of cancer‐associated fibroblast (CAF)‐released Exos on macrophage polarization in pancreatic cancer and the molecular mechanisms. THP‐1 cells or xenografted tumor mice were treated with Exos from CAFs, and macrophage polarization was analyzed using quantitative real‐time PCR (qPCR) and flow cytometry. THP‐1 cells were cocultured with BXPC‐3 cells, and metastasis was analyzed using Transwell assay and scratch test. Exosomal PTGS2 was detected using qPCR, and the NOD1 pathway was evaluated using western blot analysis. The results showed that Exos promoted M2‐type polarization and inhibited M1‐type polarization, and then facilitated pancreatic cancer cell migration, invasion, and epithelial‐mesenchymal transition. PTGS2 expression was increased in Exo‐treated macrophages, and its knockdown in CAFs facilitated M2 to M1 macrophage polarization. Moreover, Exos promoted the NOD1 pathway via PTGS2, and inhibition of NOD1 reversed the polarization caused by Exos. Additionally, NOD1 was required in M1/M2 polarization in vivo mediated by Exos. In conclusion, CAF‐secreted Exos facilitated M2 macrophage polarization by carrying PTGS2 to activate the NOD1 pathway, thereby promoting pancreatic cancer metastasis, providing evidence that CAF‐Exos accelerating pancreatic cancer progression.
Drp1‐Dependent Mitochondrial Fission Contributes to Lactic Acid‐Induced Chicken Cardiomyocyte Damage
Authors: Hu Dongfang , Cui Yunli , Hou Xueke , Wang Xueying , Shen Zihui , Pang Huiqing , Ge Yaming , Ning Hongmei
Published: January 2025

Enhanced glycolysis and elevated lactic acid (LA) production are observed during sudden death syndrome (SDS) in broilers. However, the mechanism underlying LA‐induced cardiomyocyte damage and heart failure in fast‐growing broilers remains unclear. In this study, chicken embryo cardiomyocytes (CECs) were cultured and treated with LA to investigate LA‐induced CEC injury and its mechanism, aiming to develop strategies to prevent LA‐induced SDS in broilers. Results showed that LA inhibited CEC proliferation and contraction whereas inducing apoptosis. Furthermore, LA disrupted mitochondrial ultrastructure, reduced mitochondrial membrane potential, activated mitophagy, and disturbed mitochondrial dynamics. Treatment with Mdivi‐1, a selective Drp1 inhibitor, improved CEC viability, restored mitochondrial network integrity, reduced reactive oxygen species production, and inhibited LA‐induced apoptosis. These findings suggest that LA‐induced cardiomyocyte injury during SDS in broilers is associated with mitochondrial damage and increased mitochondrial fission. The inhibition of mitochondrial hyperfission by Mdivi‐1 effectively preserves CEC morphology, structure, and function, playing a critical role in preventing LA‐induced damage. This study provides a foundation for strategies to prevent and control SDS in broilers.
Characteristics of eligible patients with knee osteoarthritis accepting versus declining participation in a randomised trial investigating the effect of weight loss versus knee arthroplasty to explore generalisability: A cross‐sectional study
Authors: Aljuboori Saber Muthanna , Christensen Robin , Henriksen Marius , Bliddal Henning , Troelsen Anders , Boesen Mikael , Poulsen Asbjørn Seenithamby , Nielsen Camilla Toft , Bunyoz Kristine Ifigenia , Overgaard Søren
Published: January 2025

Background

The INtensive diet versus Knee Arthroplasty (INKA) trial is a randomised trial assessing weight loss as an alternative to knee arthroplasty (KA) in obese patients with severe knee osteoarthritis (OA) awaiting KA (NCT05172843). The external validity of the INKA trial may be hampered if the patients who participate differ from those who decline participation.

Objective

To compare baseline characteristics between patients who enrol in the INKA trial and those who decline participation (i.e., non‐INKA [nINKA] group).

Methods

We applied a cross‐sectional study design, collecting and comparing baseline characteristics among all patients eligible for enrolment in the INKA trial from two clinics in Copenhagen. Imbalance between accepting (INKA) and declining (nINKA) groups was assessed using standardised differences (StdDs). We were prespecified that StdD values < 0.20 would indicate a clinically insignificant imbalance between groups, whereas values > 0.80 indicate incomparability.

Results

Of the 913 patients scheduled for KA, 888 were screened for INKA trial eligibility. Of the 217 eligible patients, 92 (42%) were enroled in the INKA trial, while 37 (17%) participated in the nINKA cross‐sectional sample only. Patients enroled in INKA had on average a less severe Oxford knee score (OKS) of 22.0 (standard deviation = 6.7) compared to declining participants in nINKA with 18.6 (7.2), corresponding to an StdD of 0.50, and an absolute difference of 3.45 (95% confidence interval = 0.64–6.26, p = 0.017). A consistent similar pattern was noted across all secondary patient‐reported outcomes applied in the INKA trial.

Conclusions

We observed discrepancies in patient‐reported outcomes, with those who declined enrolment reporting more severe symptoms. These differences, however, were below the minimally important difference between groups for OKS, which is set to 4.84 points.

Level of Evidence

Level II–III cross‐sectional study in a randomised control trial.
Multiple secondary stabiliser injuries increase rotational instability in anterior cruciate ligament‐deficient knees
Authors: Kato Jiro , Fukushima Hiroaki , Kensaku Abe , Hanaki Syunta , Ota Kyohei , Kawanishi Yusuke , Kobayashi Makoto , Yoshida Masahito , Takenaga Tetsuya , Kawaguchi Yohei , Kuroyanagi Gen , Sakai Hiroaki , Murakami Hideki , Nozaki Masahiro
Published: January 2025

Purpose

Medial meniscus ramp lesions (MMRLs), lateral meniscus posterior root tears (LMPRTs), and anterolateral complex injuries (ALCIs) are major secondary stabiliser injuries associated with anterior cruciate ligament (ACL) injuries. This study aimed to investigate the effect of the number of secondary stabiliser injuries on knee instability in ACL injuries.

Methods

Patients who underwent primary ACL reconstruction between January 2017 and May 2023 were enroled in this study. Exclusion criteria encompassed patients with other ligament injuries, a history of contralateral knee injury, hyperextension, flexion contracture and meniscus injuries other than MMRL or LMPRT. Ultimately, 158 patients (mean age: 25.3 years; 81 males and 77 females) were included in this study, and the presence of MMRL, LMPRT and ALCI was investigated. Patients were categorised into four groups based on the number of ACL and secondary stabiliser injuries: single (isolated ACL injury), dual, triad and tetrad. Subsequently, the groups were compared regarding pivot shift grade, quantitative rotational instability measured using an inertial sensor, and anterior tibial translation (ATT).

Results

Secondary stabiliser injuries identified included ALCI 85 (53.8%), MMRL 58 (36.7%) and LMPRT 23 (14.6%). The distribution of patients in the single, dual, triad and tetrad groups was 45 (28.5%), 68 (43.0%), 37 (23.4%) and 8 (5.1%), respectively. High‐grade pivot shifts were observed in 33.3% (15 out of 45) of the single group, 63.2% (43 out of 68) of the dual group, 67.6% (25 out of 37) of the triad group, and 100% (8 out of 8) of the tetrad group. Quantitative evaluations using the inertial sensor revealed significantly lower acceleration in the isolated ACL injury group compared to the other groups (p < 0.05). No significant difference was observed in ATT measurements (n.s.).

Conclusion

The combination of secondary stabiliser injuries led to higher instability. Therefore, it is important to carefully diagnose these injuries and devise appropriate treatment plans, particularly in cases of high knee instability.

Level of Evidence

Level III diagnostic.
Meniscal forces and knee kinematics are affected by tibial slope modifying high tibial osteotomy
Authors: Winkler Philipp W. , Chan Calvin K. , Polamalu Sene K. , Lucidi Gian Andrea , Wagala Nyaluma N. , Hughes Jonathan D. , Debski Richard E. , Musahl Volker
Published: January 2025

Purpose

To quantify the effect of increasing the posterior tibial slope (PTS) on knee kinematics and the resultant medial and lateral meniscal forces.

Methods

In this controlled laboratory study, a 6 degrees of freedom (DOF) robotic testing system was used to apply external loading conditions to seven fresh‐frozen human cadaveric knees: (1) 200‐N axial compressive load, (2) 5‐N m internal tibial +10‐N m valgus torque and (3) 5‐N m external tibial + 10‐N m varus torque. Knee kinematics and the resultant medial and lateral meniscal forces were acquired for two PTS states: (1) native PTS and (2) increased PTS. Resultant forces in the medial and lateral meniscus were calculated using the principle of superposition.

Results

In response to 5‐N m external tibial + 10‐N m varus torque, significantly more internal tibial rotation was observed after increasing PTS at 60° (p = 0.0156) and 90° (p = 0.0156) flexion. Increasing PTS caused significantly more medial tibial translation from 30° to 90° flexion in response to 5‐N m internal tibial + 10‐N m valgus torque. In response to 5‐N m external tibial + 10‐N m varus torque, the resultant force in the medial meniscus at 60° flexion decreased significantly after increasing PTS (32.8%, p = 0.016). Resultant forces in the lateral meniscus decreased significantly after increasing PTS at 30° (34.5%; p = 0.016) and 90° (29.7%; p = 0.031) flexion in response to 5‐N m internal tibial + 10‐N m valgus torque.

Conclusion

Increasing PTS in a native knee with intact cruciate ligaments affected 6 DOF knee kinematics and decreased resultant forces in the medial and lateral meniscus by up to 35% in response to combined rotatory loads. Therefore, increasing PTS during high tibial osteotomy in a knee with intact cruciate ligaments does not increase the force carried by the entire meniscus at time zero.

Level of Evidence

N/A.
Initial Boundary Value Problem for Partial Differential–Algebraic Equations With Parameter
Authors: Assanova Anar T.
Published: January 2025

The paper addresses an initial boundary value problem for a partial differential–algebraic equation involving a parameter. An integral condition with respect to the time derivative of the unknown function is provided as an additional condition to determine this parameter. The Dzhumabaev parameterization method is employed to solve the problem. The domain is subdivided, and functional parameters are defined as the values of the solution along the internal lines of the subdomains. This reformulates the original problem into an equivalent initial boundary value problem for a system of hyperbolic equations with parameters and associated functional relations. The paper develops algorithms to solve the problem, demonstrating their applicability. Furthermore, conditions for the existence and uniqueness of a solution to the initial boundary value problem, involving the partial differential–algebraic equation with a parameter and discrete memory, are established.
National and Regional Trends in Congenital Cytomegalovirus Infection From 1998 to 2019
Authors: So Raymond J. , Noij Kimberley S. , Wang Jiangxia , Walsh Jonathan , Gourin Christine G. , Jenks Carolyn M.
Published: January 2025

Objective

To analyze temporal changes and to assess the possible effect of newborn hearing screening (NBHS) programs on changes in congenital cytomegalovirus (cCMV) diagnostic rates in the United States.

Study Design

Cross‐sectional study.

Setting

National Inpatient Sample (NIS) database.

Methods

Neonates with cCMV infection were identified using discharge data from the NIS database from 1998 to 2019. Neonates with cCMV infection were identified via International Classification of Diseases codes and categorized as asymptomatic versus symptomatic and with or without hearing loss. Linear regression and interrupted time series analyses were conducted to analyze changes in diagnostic rates over time. Interrupted analyses were based on the timing of NBHS implementation in geographic regions.

Results

Per 1,000,000 live births, the estimated total number of cCMV diagnoses increased from 109 in 1998 to 250 in 2019 (the estimated annual increase per 1,000,000 live births is 6.89 ([95% confidence interval, 5.43‐8.35], P < .001). Diagnosis of cCMV with hearing loss showed a significant annual increase during this time (0.87 [0.51‐1.22], P < .001), and within this group, diagnosis of both asymptomatic (0.18 [0.03‐0.32], P = .02) and symptomatic (0.68 [0.37‐0.99], P < .001) cases increased significantly. Compared to pre‐NBHS, the rate of increase in cCMV diagnosis was significantly higher post‐NBHS implementation in the Northeast (P < .001) and South (P = .008).

Conclusion

Implementation of state NBHS programs correlated with increasing diagnosis rates of cCMV, though cCMV education and awareness may be contributing. cCMV continues to be underdiagnosed in a large national database.
Evidence‐Based Medicine in Otolaryngology Part 17: A Qualitative Research Primer
Authors: Raol Nikhila , Pattisapu Prasanth , Ikeda Allison K. , Lowers Jane , Joe Stephanie , Shin Jennifer J.
Published: January 2025

As qualitative data analysis becomes more frequently applied within the fields of medicine and surgery, it is beneficial to expand our knowledge of the utility, methodology, and interpretation of these techniques. While qualitative research serves a distinct purpose and differs from quantitative research, both can be approached with diligence, with careful techniques that are similarly maintained and respected. In advance of this installment in the Evidence‐Based Medicine in Otolaryngology series, we presented a comparison between qualitative and quantitative methods. To provide additional understanding of the specifics of qualitative research, this article presents further insights into qualitative research applications, theories, data collection methods, sources of and approaches to bias, and methods which support rigorous results.
Mycobacterium goodii pulmonary disease with organizing pneumonia: A case report and review of literature
Authors: Shionoya Yu , Kasai Hajime , Kono Reiya , Hirama Ryutaro , Ota Masayuki , Naito Akira , Abe Mitsuhiro , Kawasaki Takeshi , Ikeda Jun‐ichiro , Suzuki Takuji
Published: January 2025

Mycobacterium goodii, a rapidly growing non‐tuberculous mycobacterium, rarely causes pulmonary diseases. A patient was admitted to our hospital with a fever and cough. Chest radiography revealed consolidation in the right middle lung. As he had previously been treated for organizing pneumonia (OP), he was diagnosed with OP recurrence and administered systemic corticosteroids. Although initial improvement was observed, the pulmonary consolidations worsened. Transbronchial lung cryobiopsy revealed an OP pattern. M. goodii was identified in sputum acid‐fast bacilli cultures. The patient was diagnosed with M. goodii pulmonary disease and secondary OP. Although intravenous imipenem‐cilastatin, amikacin, and ciprofloxacin led to initial improvement in pulmonary consolidations, the consolidations re‐worsened. Systemic corticosteroids were initiated, resulting in improvement in the consolidations. The dose of systemic corticosteroids was tapered; oral antimycobacterial therapy was continued. M. goodii can cause pulmonary disease and induce OP; antimycobacterial therapy and systemic corticosteroids can be effective.
Cutting rule for in-in correlators and cosmological collider
Authors: Ema Yohei , Mukaida Kyohei
Published: January 2025

Abstract

We derive a cutting rule for equal-time in-in correlators including cosmological correlators based on Keldysh r/a basis, which decomposes diagrams into fully retarded functions and cut-propagators consisting of Wightman functions. Our derivation relies only on basic assumptions such as unitarity, locality, and the causal structure of the in-in formalism, and therefore holds for theories with arbitrary particle contents and local interactions at any loop order. As an application, we show that non-local cosmological collider signals arise solely from cut-propagators under the assumption of microcausality. Since the cut-propagators do not contain (anti-)time-ordering theta functions, the conformal time integrals are factorized, simplifying practical calculations.
Changes in gene expression align with behavioural differences in reproductive choices in a social beetle
Authors: Regon P. , Schudoma C. , Moncaz A. , Harari A. , Kliot A.
Published: January 2025

Social insects often share their colony with individuals of different relatedness levels and life stages. When no reproductive depression is in place, a female must choose whether to stay with her natal group and possibly limit her reproductive potential or leave to establish a new colony. The factors governing and following this decision are still largely unknown. The date stone beetle Coccotrypes dactyliperda (Curculiondae) resides in galleries carved inside date seeds. Sibling mating is common in this species. While most females in a natal group stay and raise their offspring with their sisters, some females leave to start a colony of their own, regardless of resources’ availability within the natal group. In this study, we hypothesized that dispersing females should present physiological changes consistent with the anticipated challenges, including finding a host and egg laying, while the physiology of females that stay in the natal seed should demonstrate physiology related to cohabiting in an existing nest. To test our hypothesis, we examined the development of ovaries in ‘stayers’ and ‘dispersers’ females. In addition, we sequenced and analysed the transcriptome of pooled groups of ‘stayers’ and ‘dispersers’ sisters. Our physiological and transcriptomic results indicate that females who left the natal seed exhibit greater ovarian development. Our transcriptomic data revealed further differences between the two groups, including higher levels of expression of cuticle-related genes in the females that chose to stay in the natal nest. We discuss the possible roles of these genes in the continued life inside the natal nest.
More micrometastases, more recurrence? The role of qPCR of PSA mRNA in lymph nodes during prostatectomy
Authors: Troidl Johannes , Fehr Alexander , Jandrig Burkhard , Köllermann Jens , Lux Anke , Baumunk Daniel , Gür Melis , Liehr Uwe-B. , Porsch Markus , Wendler Johann J. , Blaschke Simon , Schostak Martin
Published: January 2025

Background and objectives

Radical prostatectomy is a standard treatment for prostate cancer, yet about 30% of patients experience rising biochemical markers within a decade post-surgery. Pelvic lymph node sampling during prostatectomy assesses potential lymph node metastases, but standard histological assessments, which typically examine only 2–3 tissue sections, often miss occult metastases. This study assesses the effectiveness of qPCR in detecting PSA coding KLK3 mRNA for identifying lymph node metastases post-prostatectomy and explores the correlation between PSA-mRNA and biochemical recurrence.

Methods

A cohort of 157 patients who underwent radical prostatectomy with lymphadenectomy were examine. On average, 24.7 lymph nodes were removed per patient. Among them, 108 patients reached PSA value below 0.1 ng/ml without receiving additional therapy, and 106 were followed up over a duration of 5.4 years. This subgroup is of particular interest because it allows for the investigation of the correlation between the occurrence of PSA-mRNA in lymph nodes and later biochemical recurrence.

Key findings and limitations

qPCR of PSA-mRNA identified 47 out of 108 positive cases (43.5%), while histopathological examination only detected 16 out of 108 cases (14.8%). From the followed-up subgroup 37 out of 106 patients (34.9%) experienced biochemical recurrence. It is noteworthy that qPCR yields more positive findings, regardless of the presence of biochemical recurrence.

Conclusion and clinical implications

The study findings illustrate that qPCR consistently outperforms conventional histology in detecting lymph node metastases, regardless of biochemical recurrence. The hypothesis that qPCR is better at predicting later biochemical recurrence than conventional histology has not been confirmed.
A new intelligent approach for frequency controller of autonomous hybrid power systems
Authors: Magdy Gaber , Bakeer Abualkasim , Bakeer Mahmoud , Albalawi Hani , Zaid Sherif A.
Published: January 2025

An intelligent approach for load frequency control based on a proportional-integral-derivative (PID) controller, referred to as an intelligent PID (IPID) controller, is proposed to enhance the frequency stability of autonomous hybrid power systems (HPSs) considering the high penetration levels of renewables. The proposed IPID is based on the ultra-local mod4el, i.e., a model-free control, which operates independently of the power system parameters since the controller incorporates a term for unknown disturbances, enhancing its control action. Moreover, a new meta-heuristic optimization algorithm, i.e., Geometric Mean Optimizer (GMO), is used to fine-tune the proposed IPID controller parameters for frequency regulation of the studied HPS. Furthermore, the superior performance of the proposed IPID controller based on the GMO is validated by comparing it with other counterpart controllers used; such as the PID and fractional-order PID (FOPID) controllers under different load/renewables perturbations, system uncertainties, and high renewables penetration. The Matlab simulation results demonstrate that the proposed IPID controller using GMO offers greater stability in reducing response deviations compared to traditional PID and FOPID controller structures. Where the proposed IPID controller demonstrated a 80% improvement in performance compared to the traditional PID controller, and a 57% improvement over the FOPID controller in handling scenarios with random load demand and high renewables penetration. Finally, to combine the accuracy of physical simulation and the adaptability of numerical simulation, the proposed IPID controller based on the GMO is verified and implemented in a real-time environment based on the PLECS RT Box platform.
Comprehensive histopathological analysis of gastric cancer in European and Latin America populations reveals differences in PDL1, HER2, p53 and MUC6 expression
Authors: Martínez-Ciarpaglini Carolina , Barros Rita , Caballero Carmelo , Boggino Hugo , Alarcón-Molero Lorena , Peleteiro Bárbara , Ruiz-García Erika , Fernandez-Figueroa Edith , Herrera-Goepfert Roberto , Díaz-Romero Consuelo , Ferreira Rui , Groen-van Schooten Tessa S. , Gauna Cinthia , Pereira Rita , Cantero Daniel , Lezcano Horacio , Esteso Federico , O´Connor Juan , Riquelme Arnoldo , Owen Gareth I. , Garrido Marcelo , Roa Juan Carlos , Ruiz-Pace Fiorella , Vivancos Ana , Diez-García Marc , Alsina Maria , Matito Judit , Martin Agatha , Gómez Marina , Castillo Ester , Vila Maria , Santos-Antunes João , Costa Andreia , Lordick Florian , Farrés Judith , Palomar-De Lucas Brenda , Cabeza-Segura Manuel , Villagrasa Rosanna , Jimenez-Martí Elena , Miralles-Marco Ana , Dienstmann Rodrigo , Derks Sarah , Figueiredo Ceu , Cervantes Andrés , Carneiro Fátima , Fleitas-Kanonnikoff Tania
Published: January 2025

Introduction

Gastric cancer (GC) burden is currently evolving with regional differences associated with complex behavioural, environmental, and genetic risk factors. The LEGACy study is a Horizon 2020-funded multi-institutional research project conducted prospectively to provide comprehensive data on the tumour biological characteristics of gastroesophageal cancer from European and LATAM countries.

Material and methods

Treatment-naïve advanced gastroesophageal adenocarcinoma patients were prospectively recruited in seven European and LATAM countries. Formalin-fixed paraffin-embedded primary tumour endoscopic biopsy samples were collected and submitted for central morphological and immunohistochemical characterization and TP53 molecular assessment and Helicobacter pylori infection.

Results

A total of 259 patients were included in the study: 137 (53%) from LATAM and 122 (47%) from Europe. Significant biological differences were detected between European and LATAM patients. Low representation of chromosomal instability (CIN) and HER2 positive cases were found in LATAM. MUC6 and PD-L1 were more frequently overexpressed in European cases, showing a significant correlation across the entire study population, with this association being especially pronounced in MMRdeficient cases. Both TP53 mutation by next-generation sequencing and p53 immunohistochemical aberrant pattern were linked with features associated with chromosomal instability. No regional differences were observed in H. pylori prevalence or abundance, indicating that the afore mentioned variations cannot be attributed to this factor.

Conclusion

Our findings underscore a need for region-specific approaches in gastroesophageal cancer diagnosis and treatment. MUC6 emerges as a putative immune regulator that needs further investigation. Research tailored to the unique biological profiles in different global regions is crucial to effectively address the observed disparities.
Application of ultra-weak photon emission imaging in plant stress assessment
Authors: Prasad Ankush , Mihačová Eliška , Manoharan Renuka Ramalingam , Pospíšil Pavel
Published: January 2025

The oxidative damage induced by abiotic stress factors such as salinity, drought, extreme temperatures, heavy metals, pollution, and high irradiance has been studied in Arabidopsis thaliana. Ultra-weak photon emission (UPE) is presented as a signature reflecting the extent of the oxidation process and/or damage. It can be used to predict the physiological state and general health of plants. This study presents an overview of a potential research platform where the technique can be applied. The results presented can aid in providing invaluable information for developing strategies to mitigate abiotic stress in crops by improving plant breeding programs with a focus on enhancing tolerance. This study evaluates the applicability of charged couple device (CCD) imaging in evaluating plant stress and degree of damage and to discuss the advantages and limitations of the claimed non-invasive label-free tool.
Entropy Generation Rate as a Marker for the Onset of Flame Instability
Authors: Zhumabayeva Daniya , Cant Robert Stewart
Published: January 2025

A comprehensive understanding of the mechanisms of intrinsic flame instability, including hydrodynamic and thermodiffusive instabilities, is becoming more important with the move towards greater reliance on hydrogen as a zero-carbon fuel. While intrinsic flame instabilities have been studied extensively both numerically and experimentally, certain important features, including their onset, have been defined mainly by qualitative measures. This work proposes a quantitative marker to identify the onset of intrinsic flame instabilities derived from the statistics of the entropy equation. Direct numerical simulations were carried out for two-dimensional laminar premixed planar methane-air flames, with varying amounts of hydrogen addition up to 100% by volume. Entropy generation mechanisms were analysed based on contributions resulting from heat conduction, viscous dissipation, mass diffusion, and chemical reaction. Instability onset was shown to be characterised by increased data dispersion in all entropy generation terms. The dispersion was quantified by the statistical range, which increased for all locations within the flame as the flame transitioned into instability. Increasing hydrogen addition resulted in a delayed instability onset attributed to the decreasing hydrodynamic instability growth rate. The entropy generation rate due to viscous dissipation was found to be smaller in magnitude compared to other mechanisms, but it was found to be the most sensitive indicator of instability onset. This quantity is readily computed using data from numerical simulations and can be estimated from experimental data, suggesting its potential use as a marker of intrinsic flame instability.
Indirect Pathways from Sociodemographic Risk to Mothers’ Supportive Emotion Socialization via Psychological Distress and Social Cognition
Authors: Negi Shourya , Leerkes Esther M. , Sattler Kierra M. P.
Published: January 2025

Sociodemographic disadvantage is a stressor related with unsupportive parenting practices, but little is known about the process by which it may undermine early parental emotion socialization. In the current study, we examined (1) the direct association between sociodemographic risk and supportive emotion socialization and (2) possible indirect effects via psychological distress and mother-oriented cry processing (i.e., negative cognitions about crying) in a short-term 3-wave longitudinal study that followed a stratified sample of 259 first-time mothers from pregnancy through 14-months postpartum. Sociodemographic risk included mothers’ age, education, and income reported by the expectant mothers prenatally. Psychological distress was assessed prior to the 6-month laboratory visit using mothers’ reports on depressive symptoms, difficulty regulating emotions, and trait positive and negative emotions. During the 6-month laboratory visit, mother-oriented cry processing was assessed using a video-recall procedure. Supportive emotion socialization at 14 months was assessed based on observer-rated maternal sensitivity during two distress eliciting tasks and maternal reports. Consistent with prediction, the first indirect pathway from higher sociodemographic disadvantage to lower supportive emotional socialization through higher mother-oriented cry processing was statistically significant, however the second indirect pathway from higher sociodemographic disadvantage to higher psychological distress to higher mother-oriented cry processing to lower supportive emotion socialization was not. Over and above these indirect effects, higher sociodemographic disadvantage was directly associated with lower supportive emotion socialization. Psychological distress was not significantly directly associated with emotion socialization. These findings highlight the importance of policies and interventions that provide financial assistance to the mothers experiencing sociodemographic disadvantage and target their psychological wellbeing.