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Summary: The combination of brain structural and functional connectivity offers complementary insights into its organisation. Multilayer network analysis explores various relationships across different layers within a single system. We aimed to investigate changes in the structural and functional multilayer network in 69 patients with primary restless legs syndrome (RLS) compared with 50 healthy controls. Participants underwent diffusion tensor imaging (DTI) and resting state‐functional magnetic resonance imaging (rs‐fMRI) using a three‐tesla MRI scanner. We constructed a structural connectivity matrix derived from DTI using a DSI program and made a functional connectivity matrix based on rs‐fMRI using an SPM program and CONN toolbox. A multilayer network analysis, using BRAPH program, was then conducted to assess the connectivity patterns in both groups. At the global level, significant differences there were between the patients with RLS and healthy controls. The average multiplex participation was lower in patients with RLS than in healthy controls (0.804 vs. 0.821, p = 0.042). Additionally, several regions showed significant differences in the nodal level in multiplex participation between patients with RLS and healthy controls, particularly the frontal and temporal lobes. The regions affected included the inferior frontal gyrus, medial orbital gyrus, precentral gyrus, rectus gyrus, insula, superior and inferior temporal gyrus, medial and lateral occipitotemporal gyrus, and temporal pole. These results represent evidence of diversity in interactions between structural and functional connectivity in patients with RLS, providing a more comprehensive understanding of the brain network in RLS. This may contribute to a precise diagnosis of RLS, and aid the development of a biomarker to track treatment effectiveness. [ABSTRACT FROM AUTHOR]

Long-term protective effects of menopausal hormone therapy (MHT) at fractures with different doses and components are controversial. We analyzed the effect of MHT on the incidence of spine and femur fractures according to MHT type, age at commencement, duration and dose of hormones in Korean women. This retrospective study evaluated propensity score-matched patients with MHT from the Korean National Health Insurance Service database. Among women aged ≥50 years with menopause between 2004 and 2007, spine and femur fracture incidence until 2017 was analyzed in 36,446 women who had received MHT for >1 year. Estrogen–progesterone therapy (EPT), estrogen-only therapy (ET) or tibolone therapy was conducted. EPT significantly lowered the incidence of spine and femur fractures with a conventional dose, but not with a low dose. Tibolone significantly decreased the incidence of spine fractures in women aged 50–59 years when used for >5 years, and the incidence of femur fractures in women older than 60 years when used for >3 years. ET significantly lowered the risk of femur fractures when estradiol was used for >5 years. In menopausal women, all MHT including conventional-dose EPT, ET and tibolone tended to lower the incidence of fractures. The effects, however, varied with the type of fracture and type of MHT. [ABSTRACT FROM AUTHOR]

This study aimed to quantitatively assess the thickness of the peripapillary retinal nerve fiber layer (pRNFL) thickness, as well as the microvascular alterations in the macula and peripapillary regions, in optic nerve hypoplasia (ONH) patients compared to normal controls. This was achieved through the utilization of spectral-domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA), with a specific focus on elucidating the association between these structural alterations and visual acuity. We included a total of 17 eyes of 12 ONH patients, and 34 eyes of age-matched 34 healthy controls. The pRNFL thickness was quantified using SD-OCT, while OCTA facilitated the visualization and measurement of the microvascular structure images of the superficial retinal capillary plexus (SRCP), deep retinal capillary plexus (DRCP), and radial peripapillary capillary (RPC) segment in the macula and peripapillary area. pRNFL thickness was measured for eight sectors (superior, temporal, inferior, nasal, superotemporal, superonasal, inferotemporal, and inferonasal). SRCP, DRCP, and RPC were measured for four sectors (superior, temporal, inferior, and nasal). Age, gender, and spherical equivalent refractive errors were statistically adjusted for the analysis. Associations of structural parameters with visual acuity in ONH patients were analyzed using Spearman correlation analysis. pRNFL thickness was significantly thinner in ONH patients than in controls for all sectors. Vessel densities of temporal and nasal sectors in DRCP were significantly higher in ONH patients, but vessel densities of the inferior sector in RPC were significantly lower than those in controls. For all sectors, pRNFL thickness was strongly associated with visual acuity in ONH patients. ONH patients showed significant pRNFL thinning and microvascular alterations compared to controls, and pRNFL thickness was strongly associated with visual function. OCT and OCTA are useful tools for evaluating optic disc hypoplasia and its functional status. [ABSTRACT FROM AUTHOR]

Background: Adjusting the direction of the anterolateral ligament (ALL) femoral tunnel is suggested to avoid tunnel convergence during anterior cruciate ligament (ACL) reconstruction. Yet, there has been no in vivo clinical study reporting the effect of changing the direction of the ALL tunnel on the incidence of convergence with the ACL tunnel. Purpose: To report the incidence of convergence between the ACL femoral tunnel and a distally and anteriorly directed ALL femoral tunnel and to determine a safe distal angle and anterior angle. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 227 patients undergoing concomitant ALL and anatomic single-bundle ACL reconstruction between January 2020 and December 2022 were retrospectively reviewed. The tunnel convergence rate, angular orientation of the tunnels, and distance between tunnels were obtained using postoperative computed tomography. The patients were grouped based on the direction of the ALL tunnel (transverse vs distal anterior) and the presence of tunnel convergence (convergence vs no convergence). Results: The overall tunnel convergence rate was 53.3% (121/227 patients). Tunnel convergence was observed less frequently in the distal anterior group (33.7%) than in the transverse group (65.2%) (P <.001). The no convergence group showed an ALL tunnel oriented more distally (20.2°± 11.1°) and anteriorly (19.5°± 10.2°) compared with the convergence group (8.7°± 6.5° and 6.9°± 5.3°, respectively) (P =.005 and P =.008, respectively). There were no cases of tunnel convergence for ALL tunnels >24.3° distally and >25.5° anteriorly. There was no difference in the angle of the ACL femoral tunnel between all groups. Conclusion: A distally and anteriorly directed ALL femoral tunnel reduced the incidence of convergence with the ACL femoral tunnel. A distal angle >24.3° and an anterior angle >25.5° of an ALL tunnel are suggested to safely avoid convergence with the ACL tunnel. [ABSTRACT FROM AUTHOR]

Here, a new terbium-based metal–organic framework [Tb(qptca)1/2(H2qptca)1/2(H2O)2]n {H4qptca: [1,1′:4′,1′′:4′′,1′′′:4′′′,1′′′′-quinquephenyl]-2,2′′,2′′′′,5′′-tetracarboxylic acid} (referred to as SLX-3) was successfully achieved and was fully characterized by standard methods such as X-ray single crystal diffraction and powder X-ray diffraction. Preliminary results showed that it has excellent aqueous solution and thermal stability, and can accurately and efficiently detect MnO4− in water through a fluorescence quenching effect with excellent anti-interference and good recyclability. Moreover, the fluorescence quenching caused by the energy competition between SLX-3 and the analyte was explained by UV-Vis absorption spectroscopy and TEM-EDS spectroscopy. [ABSTRACT FROM AUTHOR]

The prefrontal cortex (PFC) has been extensively studied in relation to various cognitive abilities, including executive function, attention, and memory. Nevertheless, there is a gap in our scientific knowledge regarding the functionally dissociable neural dynamics across the PFC during a cognitive task and their individual differences in performance. Here, we explored this possibility using a delayed match‐to‐sample (DMTS) working memory (WM) task using NIRSIT, a high‐density, wireless, wearable functional near‐infrared spectroscopy (fNIRS) system. First, upon presentation of the sample stimulus, we observed an immediate signal increase in the ventral (orbitofrontal) region of the anterior PFC, followed by activity in the dorsolateral PFC. After the DMTS test stimulus appeared, the orbitofrontal cortex activated once again, while the rest of the PFC showed overall disengagement. Individuals with higher accuracy showed earlier and sustained activation of the PFC across the trial. Furthermore, higher network efficiency and functional connectivity in the PFC were correlated with individual WM performance. Our study sheds new light on the dynamics of PFC subregional activity during a cognitive task and its potential applicability in explaining individual differences in experimental, educational, or clinical populations. Practitioner Points: Wearable functional near‐infrared spectroscopy (fNIRS) captured dissociable temporal dynamics across prefrontal subregions during a delayed match‐to‐sample task.Anterior regions of the orbitofrontal cortex (OFC) activated first during the delay period, followed by the dorsolateral prefrontal cortex (PFC).PFC disengaged overall after the delay, but the OFC reactivated to the test stimulus.Earlier and sustained activation of PFC was associated with better accuracy.Functional connectivity and network efficiency also varied with task performance. [ABSTRACT FROM AUTHOR]

The poor electrochemical activity and low wettability of graphite felt (GF) electrodes significantly limit the energy efficiency and power of vanadium redox flow batteries (VRFBs). To solve these problems, we developed an N-doped porous carbon-coated electrode by the carbonization of zeolitic imidazolate framework-8- (ZIF-8-) coated GF. By controlling the carbonization temperature, the effects of temperature on the structural morphology, pore structure, and amount and type of functional groups of the electrode were confirmed. In addition, the effect of the change in the pore structure and the amount and type of functional groups on the electrocatalytic activity for the vanadium redox reaction was demonstrated. The synthesized N-doped porous carbon-coated electrode, which showed the best electrochemical activity, had a sufficient amount of nitrogen functional groups with a high ratio of graphitic N and the highest surface area and pore volume among all the samples, providing abundant active sites for the VO2+/VO2+ redox reaction. The VRFB fabricated using prepared electrode exhibited energy and voltage efficiencies of 70.44% and 73.44%, respectively, at 200 mA cm-2, which were 11.77% and 11.08% higher than those of the bare GF electrode. Furthermore, the modified battery operated effectively at a high current density of 350 mA cm-2. The energy efficiency exhibited excellent stability over 500 charge/discharge cycles at 250 mA cm-2. Hence, this study presents a promising method for the development of high-performance VRFB electrodes. [ABSTRACT FROM AUTHOR]

Sulfate crystals typically exhibit minimal optical anisotropy due to the near‐zero polarizability anisotropy (δ) of [SO4]2− tetrahedra, arising from highly symmetrical electron clouds. Recent research sought to enhance δ via chemical modifications, such as fluorination. However, the resultant crystals often maintain subpar optical anisotropy, frequently with birefringence values below 0.1. In this study, we have uncovered that δ can be significantly strengthened by chemically tailoring the tetrahedral [SO4]2− with anisotropic π‐conjugated modules. This has been demonstrated by several newly proposed S−O‐Org (Org: π‐conjugated organic species) moieties, which show a sharp increase in δ based on theoretical computations. To further validate this experimentally, we synthesized and characterized six new 3‐pyridinesulfonate crystals with the formula A(3‐C5H4NSO3) ⋅ xH2O (A=Li, Ag, K, Rb, Cs, and NH4; x=0 and 1). Notably, these materials exhibit strong optical anisotropy, with birefringence values ranging from 0.240 to 0.312 at 546 nm. These values are approximately 23 to 145.5 times greater than those of corresponding sulfates, and they outperform a vast number of sulfate‐related optical materials, thus verifying the effectiveness of the proposed strategy. Furthermore, the title compounds exhibit diverse microstructure peculiarities influenced by the size and binding natures of the counter cations. [ABSTRACT FROM AUTHOR]

Sulfate crystals typically exhibit minimal optical anisotropy due to the near‐zero polarizability anisotropy (δ) of [SO4]2− tetrahedra, arising from highly symmetrical electron clouds. Recent research sought to enhance δ via chemical modifications, such as fluorination. However, the resultant crystals often maintain subpar optical anisotropy, frequently with birefringence values below 0.1. In this study, we have uncovered that δ can be significantly strengthened by chemically tailoring the tetrahedral [SO4]2− with anisotropic π‐conjugated modules. This has been demonstrated by several newly proposed S−O‐Org (Org: π‐conjugated organic species) moieties, which show a sharp increase in δ based on theoretical computations. To further validate this experimentally, we synthesized and characterized six new 3‐pyridinesulfonate crystals with the formula A(3‐C5H4NSO3) ⋅ xH2O (A=Li, Ag, K, Rb, Cs, and NH4; x=0 and 1). Notably, these materials exhibit strong optical anisotropy, with birefringence values ranging from 0.240 to 0.312 at 546 nm. These values are approximately 23 to 145.5 times greater than those of corresponding sulfates, and they outperform a vast number of sulfate‐related optical materials, thus verifying the effectiveness of the proposed strategy. Furthermore, the title compounds exhibit diverse microstructure peculiarities influenced by the size and binding natures of the counter cations. [ABSTRACT FROM AUTHOR]

Simple Summary: Research on the clinical impact of body composition parameters, such as myosteatosis, in patients with hepatocellular carcinoma (HCC) is limited. Our study examined the effects of computed tomography-based body composition measurements and traditional risk factors on the survival outcomes of sorafenib-treated HCC patients. Myosteatosis, evaluated using Hounsfield units, is associated with unfavorable survival outcomes, independent of traditional risk factors including vascular invasion, extrahepatic metastasis, and high alpha-fetoprotein levels. Two or more of these risk factors are associated with adverse outcomes. Thus, myosteatosis could serve as a prognostic factor in sorafenib-treated HCC patients. The role of body composition parameters in sorafenib-treated hepatocellular carcinoma (HCC) patients is still not fully elucidated. Here, we aimed to evaluate the impact of computed tomography (CT)-based body composition parameters on the survival of such patients. In this multicenter study, we analyzed the data of 245 sorafenib-treated HCC patients from January 2008 to December 2019. Sarcopenia, visceral obesity, and myosteatosis were defined by using cross-sectional CT images at the third lumbar vertebra level. The effects of these parameters on overall survival (OS) and progression-free survival (PFS) were evaluated. The median age was 67.0 years (interquartile range: 61.0–78.0 year), and 211 patients (86.1%) were male. The median OS and PFS were 7.9 months and 4.8 months, respectively. Vascular invasion (hazard ratio (HR), 1.727; 95% confidence interval (CI), 1.258–2.371; p = 0.001), extrahepatic metastasis (HR, 1.401; 95% CI, 1.028–1.908; p = 0.033), alpha-fetoprotein level > 200 ng/mL (HR, 1.559; 95% CI, 1.105–2.201; p = 0.012), and myosteatosis (HR, 1.814; 95% CI, 1.112–2.960; p = 0.017) were associated with OS. Patient mortality was significantly higher in the group with two or more risk factors than in the group with fewer risk factors. In conclusion, myosteatosis may be a novel prognostic CT-based radiological biomarker in sorafenib-treated HCC patients. [ABSTRACT FROM AUTHOR]

Mitophagy stimulation has been shown to have a therapeutic effect on various neurodegenerative diseases. However, nontoxic mitophagy inducers are still very limited. In this study, we found that the natural alkaloid berberine exhibited mitophagy stimulation activity in various human cells. Berberine did not interfere with mitochondrial function, unlike the well-known mitophagy inducer carbonyl cyanide m-chlorophenyl hydrazone (CCCP), and subsequently induced mitochondrial biogenesis. Berberine treatment induced the activation of adenosine monophosphate-activated protein kinase (AMPK), and the AMPK inhibitor compound C abolished berberine-induced mitophagy, suggesting that AMPK activation is essential for berberine-induced mitophagy. Notably, berberine treatment reversed mitochondrial dysfunction in PINK1 knockout mouse embryonic fibroblasts. Our results suggest that berberine is a mitophagy-specific inducer and can be used as a therapeutic treatment for neurodegenerative diseases, including Parkinson's disease, and that natural alkaloids are potential sources of mitophagy inducers. [ABSTRACT FROM AUTHOR]

Addictions are thought to be fostered by the emergence of poorly regulated mesocorticolimbic responses to drug‐related cues. The development and persistence of these responses might be promoted by altered glutamate transmission, including changes to type 5 metabotropic glutamate receptors (mGluR5s). Unknown, however, is when these changes arise and whether the mGluR5 and mesocorticolimbic alterations are related. To investigate, non‐dependent cocaine polydrug users and cocaine‐naïve healthy controls underwent a positron emission tomography scan (15 cocaine users and 14 healthy controls) with [11C]ABP688, and a functional magnetic resonance imaging scan (15/group) while watching videos depicting activities with and without cocaine use. For some drug videos, participants were instructed to use a cognitive strategy to lower craving. Both groups exhibited drug cue‐induced mesocorticolimbic activations and these were larger in the cocaine polydrug users than healthy controls during the session's second half. During the cognitive regulation trials, the cocaine users' corticostriatal responses were reduced. [11C]ABP688 binding was unaltered in cocaine users, relative to healthy controls, but post hoc analyses found reductions in those with 75 or more lifetime cocaine use sessions. Finally, among cocaine users (n = 12), individual differences in prefrontal [11C]ABP688 binding were associated with midbrain and limbic region activations during the regulation trials. Together, these preliminary findings raise the possibility that (i) recreational polydrug cocaine users show biased brain processes towards cocaine‐related cues and (ii) repeated cocaine use can lower cortical mGluR5 levels, diminishing the ability to regulate drug cue responses. These alterations might promote susceptibility to addiction and identify early intervention targets. [ABSTRACT FROM AUTHOR]

Utilizing "You only look once" (YOLO) v4 AI offers valuable support in fracture detection and diagnostic decision-making. The purpose of this study was to help doctors to detect and diagnose fractures more accurately and intuitively, with fewer errors. The data accepted into the backbone are diversified through CSPDarkNet-53. Feature maps are extracted using Spatial Pyramid Pooling and a Path Aggregation Network in the neck part. The head part aggregates and generates the final output. All bounding boxes by the YOLO v4 are mapped onto the 3D reconstructed bone images after being resized to match the same region as shown in the 2D CT images. The YOLO v4-based AI model was evaluated through precision–recall (PR) curves and the intersection over union (IoU). Our proposed system facilitated an intuitive display of the fractured area through a distinctive red mask overlaid on the 3D reconstructed bone images. The high average precision values (>0.60) were reported as 0.71 and 0.81 from the PR curves of the tibia and elbow, respectively. The IoU values were calculated as 0.6327 (tibia) and 0.6638 (elbow). When utilized by orthopedic surgeons in real clinical scenarios, this AI-powered 3D diagnosis support system could enable a quick and accurate trauma diagnosis. [ABSTRACT FROM AUTHOR]

The perovskite manganese oxide, La 0.7 Sr 0.3 Mn 1+ x O 3 (x = −0.4, −0.2, 0, 0.2, 0.4, 0.6, 0.8, 1.0), was synthesized using the solid-state reaction method. A single-phase perovskite structure was obtained at the stoichiometric composition (x = 0). However, with an increase in Mn excess (x > 0), secondary phases of Mn 2 O 3 and Mn 3 O 4 formed and increased, while La 2 O 3 and Sr-rich phases emerged when Mn is deficient (x < 0). The electrical conductivity, permittivity, and permeability of the samples showed significant variations with x , as both charge transport and magnetism originate from the presence of Mn. Complex permittivity (ε', ε") and permeability (μ', μ") spectra were utilized to calculate RL maps based on a transmission line theory. For samples with x ≥ 0, which exhibited relatively high values of ε' and ε", there was no significant absorption of electromagnetic (EM) waves within the measured frequency range (0.1 ≤ f ≤ 18 GHz) due to high EM wave reflection. Conversely, the Mn-deficient samples (x = −0.2, −0.4) demonstrated excellent EM wave absorption properties in the GHz range. This can be attributed to their favorable impedance matching characteristics, resulting from significantly reduced ε' and ε" values in the Mn-deficient samples. Notably, the sample with x = −0.2 exhibited the most outstanding EM wave absorption characteristics, with an RL value of −56 dB at a frequency of 2.33 GHz and a thickness of 7.59 mm. Additionally, it achieved an RL value of −50 dB at 9.8 GHz and 2.90 mm thickness. [ABSTRACT FROM AUTHOR]

Introduction: The aims of this study were to evaluate 1) glymphatic system function in patients with end-stage kidney disease (ESKD) before initiating dialysis compared to healthy controls, and 2) changes in the glymphatic system function after kidney replacement therapy including dialysis in patients with ESKD using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. Materials and methods: This study was prospectively conducted at a single hospital. We enrolled 14 neurologically asymptomatic patients who first initiated hemodialysis or peritoneal dialysis for ESKD and 17 healthy controls. Patients had magnetic resonance imaging scans before initiating dialysis and again 3 months after initiating dialysis and the DTI-ALPS index was calculated. We compared the DTI-ALPS index before and after the initiation of dialysis and compared the DTI-ALPS index between the patients with ESKD and healthy control. Results: There were differences in the DTI-ALPS index between ESKD patients before initiating dialysis and healthy controls (1.342 vs. 1.633, p = 0.003). DTI-ALPS index between ESKD patients before initiating dialysis and those after dialysis were not different (1.342 vs. 1.262, p = 0.386). There was a positive correlation between DTI-ALPS index and phosphate (r = 0.610, p = 0.020) in patients with ESKD. Conclusion: We confirmed the presence of glymphatic dysfunction in patients with ESKD. However, there was no difference in the glymphatic system before and after dialysis initiation. This finding may be related to uremic toxins that are not removed by dialysis in patients with ESKD. This study can be used for the development of pathophysiology of patients with ESKD. [ABSTRACT FROM AUTHOR]

Barium sulfate and iohexol are commonly used as contrast agents for videofluoroscopic swallowing study (VFSS). This study compared their usefulness as contrast agents in visualizing components of swallowing predictable of subsequent pneumonia and unintentional weight loss after VFSS. This was a randomized, controlled, crossover trial. The two contrast agents were alternately used in the same participants, and the order in which the contrast agent was tested first was randomly assigned. After VFSS, we followed the participants for 3 months and the association between VFSS findings of each contrast agent and the subsequent pneumonia and unintentional weight loss were analyzed. A total of 30 participants were included in the analysis. We recorded 11 cases of subsequent pneumonia and 13 of unintentional weight loss. Regarding the risk of subsequent pneumonia after VFSS, only the oral transit time and number of swallows tested with barium sulfate indicated significant differences between participants with and without subsequent pneumonia. For unintentional weight loss, oral transit time and pharyngeal wall coating after swallowing tested with barium sulfate, as well as oral transit time, nasal penetration, residue in the valleculae, PAS scores, and number of swallows when testing with iohexol demonstrated significant differences between those with and without unintentional weight loss. [ABSTRACT FROM AUTHOR]

We aimed to investigate alterations in cerebellar volume and the intrinsic cerebellar network in patients with restless legs syndrome (RLS). We recruited 69 patients with RLS and 50 healthy controls who underwent brain magnetic resonance imaging (MRI), including three-dimensional T1-weighted imaging. The total cerebellar volume and cerebellar volume subdivisions were analyzed through automatic cerebellum anatomical parcellation using U-Net with locally constrained optimization program. The intrinsic cerebellar network was calculated through brain analysis using a graph theory program based on the cerebellar volume subdivisions. The cerebellar volumes and intrinsic cerebellar networks were compared between patients with RLS and healthy controls. The cerebellar volume and subdivisions in patients with RLS did not show significant differences compared to those in healthy controls. However, significant alterations were observed in the intrinsic cerebellar network of patients with RLS. Increased mean clustering coefficient (0.185 vs. 0.114; p = 0.047) and small-worldness index (0.927 vs. 0.800; p = 0.047) were observed in patients with RLS. Additionally, total cerebellar volume was negatively correlated with the Pittsburgh Sleep Quality Index (r = −0.398; p = 0.020) and Insomnia Severity Index (ISI; r = −0.396; p = 0.011). Negative correlations were additionally observed between the right X lobule volume and the International Restless Legs Syndrome Severity Scale (r = −0.425; p = 0.008) and between the vermis VIII volume and ISI score (r = −0.399; p = 0.011). We demonstrated alterations in the intrinsic cerebellar network in patients with RLS compared with healthy controls, showing increased connectivity with increased segregation in patients with RLS. This suggests a potential role of the cerebellum in RLS pathophysiology. • We aimed to explore the connection between RLS and the cerebellum by analyzing cerebellar volume and its intrinsic network. • There were no differences in cerebellar volume, RLS patients showed notable changes in their intrinsic cerebellar network. • Correlations were found between specific cerebellar regions' volumes and RLS severity as well as sleep-related indices. [ABSTRACT FROM AUTHOR]

Poly (ADP-ribose) polymerase (PARP) inhibitors are effective against BRCA1/2-mutated cancers through synthetic lethality. Unfortunately, most cases ultimately develop acquired resistance. Therefore, enhancing PARP inhibitor sensitivity and preventing resistance in those cells are an unmet clinical need. Here, we investigated the ability of paraspeckle component 1 (PSPC1), as an additional synthetic lethal partner with BRCA1/2, to enhance olaparib sensitivity in preclinical models of BRCA1/2-mutated breast and ovarian cancers. In vitro, the combined olaparib and PSPC1 small interfering RNA (siRNA) exhibited synergistic anti-proliferative activity in BRCA1/2-mutated breast and ovarian cancer cells. The combination therapy also demonstrated synergistic tumor inhibition in a xenograft mouse model. Mechanistically, olaparib monotherapy increased the expressions of p-ATM and DNA-PKcs, suggesting the activation of a DNA repair pathway, whereas combining PSPC1 siRNA with olaparib decreased the expressions of p-ATM and DNA-PKcs again. As such, the combination increased the formation of γH2AX foci, indicating stronger DNA double-strand breaks. Subsequently, these DNA-damaged cells escaped G2/M checkpoint activation, as indicated by the suppression of p-cdc25C (Ser216) and p-cdc2 (Tyr15) after combination treatment. Finally, these cells entered mitosis, which induced increased apoptosis. Thus, this proves that PSPC1 inhibition enhances olaparib sensitivity by targeting DNA damage response in our preclinical model. The combination of olaparib and PSPC1 inhibition merits further clinical investigation to enhance PARP inhibitor efficacy. [ABSTRACT FROM AUTHOR]

Although proteinuria is a risk factor for heart failure (HF), proteinuria can be reversible or persistent. Our objective was to explore the link between changes in the proteinuria status and the risk of HF. We included participants from a Korean national health screening cohort who underwent health examinations in 2003–2004 and 2005–2006 and had no history of HF. Participants were categorized into four groups: proteinuria-free, proteinuria-resolved, proteinuria-developed, and proteinuria-persistent. The outcome of interest was the occurrence of HF. The study included 1,703,651 participants, among whom 17,543 (1.03%) were in the proteinuria-resolved group and 4585 (0.27%) were in the proteinuria-persistent group. After a median follow-up period of 14.04 years (interquartile range 14.19–15.07), HF occurred in 75,064 (4.41%) participants. A multivariable Cox proportional hazards regression analysis indicated that the proteinuria-persistent group had a higher risk of HF compared with the proteinuria-free group (hazard ratio (HR): 2.19, 95% confidence interval (CI): 2.03–2.36, p < 0.001). In a further pairwise comparison analysis, participants in the proteinuria-resolved group had a relatively low risk of HF compared with those in the proteinuria-persistent group (HR: 0.64, 95% CI: 0.58–0.70, p < 0.001). In conclusion, the risk of HF can change with alterations in the proteinuria status. [ABSTRACT FROM AUTHOR]

We investigated the attributes and attribute levels that affect researcher preferences for chemical compounds. We conducted a conjoint analysis on survey data of Korean researchers using chemical compounds from the Korean Chemical Bank (KCB). The analysis estimated the part-worth utility for each attribute's level, calculated relative importance of attributes, and classified user segmentation with different patterns. The results show that the structure database offers the highest part-worth utility to researchers, followed by high new functionality, price, screening service, and drug action data provided only by the KCB. Notably, researchers view the offer of a structured database and high new functionality as more important than other attributes in decision-making about research and development of chemical compounds. Furthermore, the results of segmentation analysis demonstrated that researchers have distinct usage patterns of chemical compounds: researchers consider structure database and high new functionality in cluster 1; and high new functionality and price in cluster 2, to be the most appealing. We discussed some policy and strategic implications based on the findings of this study and proposed some limitations. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the global leading cancer burden in women and the hormone receptor-positive (HR+) subtype is a major part of breast cancer. Though cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are highly effective therapy for HR+ subtype, acquired resistance is inevitable in most cases. Herein, we investigated the paternally expressed gene 10 (PEG10)-associated mechanism of acquired resistance to CDK4/6 inhibitors. Methods: Palbociclib-resistant cells were generated by exposing human HR+ breast cancer cell lines to palbociclib for 7–9 months. In vitro mechanistic study and in vivo xenograft assay were performed. For clinical relevance, public mRNA microarray data sets of early breast cancer were analyzed and PEG10 immunohistochemical staining was performed using pre-CDK4/6 inhibitor tumor samples. Results: We observed that PEG10 was significantly upregulated in palbociclib-resistant cells. Ectopic overexpression of PEG10 in parental cells caused CDK4/6 inhibitor resistance and enhanced epithelial–mesenchymal transition (EMT). On the contrary, PEG10-targeting siRNA or antisense oligonucleotides (ASOs) combined with palbociclib synergistically inhibited proliferation of palbociclib-resistant cells and growth of palbociclib-resistant xenograft in mice and suppressed EMT as well. The mechanistic study confirmed that high PEG10 expression suppressed p21, a natural CDK inhibitor, and SIAH1, a post-translational degrader of ZEB1, augmenting CDK4/6 inhibitor resistance. Then PEG10 siRNA combined with palbociclib suppressed cell cycle progression and EMT via activating p21 and SIAH1, respectively. Consequently, combined PEG10 inhibition and palbociclib overcame CDK4/6 inhibitor resistance. Furthermore, high PEG10 expression was significantly associated with a shorter recurrence-free survival (RFS) based on public mRNA expression data. In pre-CDK4/6 inhibitor treatment tissues, PEG10 positivity by IHC also showed a trend toward a shorter progression-free survival (PFS) with CDK4/6 inhibitor. These results support clinical relevance of PEG10 as a therapeutic target. Conclusions: We demonstrated a novel PEG10-associated mechanism of CDK4/6 inhibitor resistance. We propose PEG10 as a promising therapeutic target for overcoming PEG10-associated resistance to CDK4/6 inhibitors. [ABSTRACT FROM AUTHOR]

Palmatine, a natural alkaloid found in various plants, has been reported to have diverse pharmacological and biological effects, including anti-inflammatory, antioxidant, and cardiovascular effects. However, the role of palmatine in mitophagy, a fundamental process crucial for maintaining mitochondrial function, remains elusive. In this study, we found that palmatine efficiently induces mitophagy in various human cell lines. Palmatine specifically induces mitophagy and subsequently stimulates mitochondrial biogenesis. Palmatine did not interfere with mitochondrial function, similar to CCCP, suggesting that palmatine is not toxic to mitochondria. Importantly, palmatine treatment alleviated mitochondrial dysfunction in PINK1-knockout MEFs. Moreover, the administration of palmatine resulted in significant improvements in cognitive function and restored mitochondrial function in an Alzheimer's disease mouse model. This study identifies palmatine as a novel inducer of selective mitophagy. Our results suggest that palmatine-mediated mitophagy induction could be a potential strategy for Alzheimer's disease treatment and that natural alkaloids are potential sources of mitophagy inducers. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Medication‐related osteonecrosis of the jaw (MRONJ) is uncommon but can result in severe destruction of the jaw. This case–control study investigated the therapeutic effects of daily or weekly administration of teriparatide in the management of MRONJ using a cohort for osteonecrosis of the jaw.Patients who were diagnosed with MRONJ and consented to teriparatide administration were assigned either to a group of daily injection or of weekly injection and completed a 4‐week course of injection preoperatively and at least an 8‐week course postoperatively. The control group received either the intraoperative rhBMP treatment (CG_BMP) or no additional perioperative treatment (CG_noBMP). The state of MRONJ was evaluated 2 months (T1) and 6 months (T2) postoperatively for all participants.Either group of daily injection (8.35 weeks ± 1.58; n = 17) or weekly injection (9.17 ± 3.79; n = 12) showed significantly faster healing than those of CG_BMP (14.40 ± 6.08; n = 25) or CG_noBMP (15.79 ± 9.79; n = 39). MRONJ was resolved completely in 24 out of 29 participants who completed the course of teriparatide injections, whereas 46.9% of CG showed delayed resolution. Multiple regression analysis indicated 7.50 times (95% CI, 1.77–31.82) more likelihood of complete resolution of MRONJ for participants with teriparatide injections.A course of daily or weekly administration of teriparatide injections may improve treatment outcomes for patients with MRONJ. [ABSTRACT FROM AUTHOR]

We compared the efficacy and safety of autologous-serum (AS) and platelet-rich plasma (PRP) eye drops for dry eye (DE) treatment in primary Sjögren's syndrome (SS). This prospective, randomized, double-blinded clinical study included patients diagnosed with primary SS DE. Thirty-eight participants were randomly assigned to the AS or PRP groups. Corneal and conjunctival staining scores, Schirmer I test, tear film break-up time (TBUT), and ocular surface disease index (OSDI) scores were evaluated at 4 and 12 weeks. Conjunctival impression cytology (CIC) metaplasia grade and goblet cell density grade at 12 weeks were compared with those at baseline. Corneal and conjunctival staining scores and TBUT significantly improved at 4 and 12 weeks in both groups (all p < 0.005). No significant difference between the AS and PRP groups was observed at 4 and 12 weeks. The Schirmer I values, OSDI scores, CIC metaplasia grade, and goblet cell density grade did not significantly change at 4 and 12 weeks in either group. Both AS and PRP eye drops are effective for primary SS DE without a significant difference. Considering that the preparation time of PRP is shorter than that of AS, PRP can be a good alternative treatment for primary SS DE. [ABSTRACT FROM AUTHOR]

Background: Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). Methods: A multicenter randomized phase II trial involving 364 patients with LARC (cT3–4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45–50.4 Gy in 25–28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2–5 weeks from the last cycle of chemotherapy in the experimental arm and 6–8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. Discussion: This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. Trial registration: This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023. [ABSTRACT FROM AUTHOR]

This prospective study investigated white matter tracts associated with restless legs syndrome (RLS) severity in 69 patients with primary RLS using correlational tractography based on diffusion tensor imaging. Fractional anisotropy (FA) and quantitative anisotropy (QA) were analyzed separately to understand white matter abnormalities in RLS patients. Connectometry analysis revealed positive correlations between RLS severity and FA values in various white matter tracts, including the left and right cerebellum, corpus callosum forceps minor and major, corpus callosum body, right cingulum, and frontoparietal tract. In addition, connectometry analysis revealed that the FA of the middle cerebellar peduncle, left inferior longitudinal fasciculus, left corticospinal tract, corpus callosum forceps minor, right cerebellum, left frontal aslant tract, left dentatorubrothalamic tract, right inferior longitudinal fasciculus, left corticostriatal tract superior, and left cingulum parahippocampoparietal tract was negatively correlated with RLS severity in patients with RLS. However, there were no significant correlations between QA values and RLS severity. It is implied that RLS symptoms may be potentially reversible with appropriate treatment. This study highlights the importance of considering white matter alterations in understanding the pathophysiology of RLS and in developing effective treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: Residual anterior knee pain is one of the most common problems after total knee arthroplasty (TKA). However, the contributing factors affecting postoperative anterior knee pain (AKP) remain poorly understood. This study aimed to evaluate the effect of preoperative patellar bone marrow lesions (BMLs) and patellar cartilage defects on postoperative AKP after patellar non-resurfacing TKA. Methods: This retrospective study included 336 patients who underwent unilateral TKA without patella resurfacing. All patients underwent preoperative magnetic resonance imaging (MRI) to assess the presence of BMLs and the degree of cartilage defects in the patella. Patients were categorized into four groups according to the presence of BMLs (with or without BMLs) and the degree of cartilage defects (with or without full thickness cartilage defects). The Kujala Anterior Knee Pain Scale (AKPS) and the Hospital for Special Surgery Knee Rating Scale (HSS) scores at 2 years after TKA were compared among the groups. Results: Preoperative BMLs in the patella were found in 132 (39.3%) of 336 cases. Among the four groups, the group with both BMLs and full-thickness cartilage defects demonstrated significantly lower AKPS compared to the other groups at 2 years after TKA (p < 0.01), but no significant difference was shown in the HSS scores, between these groups. There were no significant differences in either AKPS or HSS scores among the other three patient groups. Conclusions: The presence of preoperative BMLs with full-thickness cartilage defects in the patella was associated with worse postoperative AKP after TKA without patella resurfacing. Patella resurfacing should be considered in this patient group to minimize the risk of developing residual AKP after TKA. Level of evidence: III. [ABSTRACT FROM AUTHOR]

The west Henan region, China, has experienced four historical moderate-to-strong earthquakes. Many micro-earthquakes continue to occur in this area. However, due to inaccurate positioning of the micro-earthquake epicenters and lacking geophysical data, the initial mechanism of seismogenesis for this region is still indefinable. Here, we investigated the electrical resistivity structures of the crust using magnetotelluric (MT) data collected in the west Henan region. The electrical resistivity model obtained by 3D inversion of MT data shows moderately resistive features in the lower crust and a conductive body in the upper crust (10–25 km). Furthermore, we combined the accurately relocated hypocenter locations for micro-earthquakes using the double-difference earthquake relocation algorithm (hypoDD) to further understand the seismogenic setting, revealing that earthquakes occur either near the surroundings of the conductor or around faults, but do not happen in the zones where both conductor and faults are distributed. The possible cause of earthquakes occurring around the conductor and the moderate historical earthquake happening in the study area is the change in crustal viscosity. The concentration of micro-earthquake hypocenters in the vicinity of faults may result from both the uneven stress in the crust and fluid flow in and out of the fault fracture zones along with fault movement. The origin of a few events distributed in the zones with both the conductor and fault distribution may be the release of stress in time through faults. [ABSTRACT FROM AUTHOR]

The subchondral bone is an important part of cartilage which contains a large amount of hydroxyapatite. The mineral components of subchondral bone is the key factor which determines the biomechanical strength, and then affects the biological function of articular cartilage. Here, a mineralized polyacrylamide (PAM-Mineralized) hydrogel with good ALP activity, cell adhesion and biocompatibility was fabricated for subchondral bone tissue engineering. The micromorphology, composition and mechanical properties of PAM and PAM-Mineralized hydrogels were studied. The PAM hydrogels showed a porous structure, while the PAM-Mineralized hydrogels had well-distributed layers of hydroxyapatite mineralization on the surface. The XRD results show that the characteristic peak of hydroxyapatite (HA) was measured in PAM-Mineralized, indicating that the main component of the mineralized structure formed on the surface of the hydrogel after mineralization is HA. The formation of HA ectively decreased the rate of equilibrium swelling of the PAM hydrogel, with PAM-M reaching swelling equilibrium at 6 h. Meanwhile, compressive strength of PAM-Mineralized hydrogel (moisture state) reached 290 ± 30 kPa, compressive modulus reached 130 ± 4 kPa. PAM-Mineralized hydrogels did not affect the growth and proliferation of MC3T3-E1 cells. Surface mineralization of PAM hydrogel could significantly improve osteogenic differentiation of MC3T3-E1 cells. These results showed that PAM-Mineralized hydrogel could possess potential application in the field of subchondral bone tissue engineering. [ABSTRACT FROM AUTHOR]

Ovarian aging is a major obstacle in assisted reproductive medicine because it leads to ovarian dysfunction in women of advanced age. Currently, there are no effective treatments to cure age-related ovarian dysfunction. In this study, we investigated the effect of MIT-001 on the function of aged ovaries. Young and old mice were utilized in this study. MIT-001 was intraperitoneally administered, and the number of follicles and oocytes was analyzed. Each group was then retrieved for RNA and protein isolation. Total RNA was subjected to mRNA next-generation sequencing. Protein extracts from ovarian lysates were used to evaluate various cytokine levels in the ovaries. MIT-001 enhanced follicles and the number of oocytes were compared with non-treated old mice. MIT-001 downregulated immune response-related transcripts and cytokines in the ovaries of old mice. MIT-001 modulates the immune complex responsible for generating inflammatory signals and has the potential to restore the function of old ovaries and improve female fertility. [ABSTRACT FROM AUTHOR]

(1) Background: High-grade serous ovarian carcinoma (HGSOC) is an aggressive subtype of ovarian cancer. Recent advances have introduced prognostic markers and targeted therapies. Programmed cell death ligand 1 (PD-L1) has emerged as a potential biomarker for HGSOC, with implications for prognosis and targeted therapy eligibility; (2) Methods: A literature search was conducted on major databases, and extracted data were categorized and pooled. Subgroup analysis was performed for studies with high heterogeneity. (3) Results: Data from 18 eligible studies were categorized and pooled based on PD-L1 scoring methods, survival analysis types, and endpoints. The result showed an association between high PD-L1 expression and a favorable prognosis in progression-free survival (HR = 0.53, 95% CI = 0.35–0.78, p = 0.0015). Subgroup analyses showed similar associations in subgroups of neoadjuvant chemotherapy patients (HR = 0.6, 95% CI = 0.4–0.88, p = 0.009) and European studies (HR = 0.59, 95% CI = 0.42–0.82, p = 0.0017). In addition, subgroup analyses using data from studies using FDA-approved PD-L1 antibodies suggested a significant association between favorable prognosis and high PD-L1 expression in a subgroup including high and low stage data in overall survival data (HR = 0.46, 95% CI = 0.3–0.73, p = 0.0009). (4) Conclusions: This meta-analysis revealed a potential association between high PD-L1 expression and favorable prognosis. However, caution is warranted due to several limitations. Validation via large-scale studies, with mRNA analysis, whole tissue sections, and assessments using FDA-approved antibodies is needed. [ABSTRACT FROM AUTHOR]

Arc-sprayed Fe-based coatings can provide a cheaper and more effective way of protecting cutting tools made of 65Mn steel against abrasive wear. Due to contact with hard and rocky soils, rotary tiller blades face extreme surface wear that reduces their service life. In this study, a new Fe-based coating was prepared on 65Mn steel substrates using arc spraying process. The influence of the process variables (spray distance, voltage, and current) on the microhardness and porosity was studied based on the response surface methodology (RSM). By maximizing microhardness and minimizing porosity, the optimum spraying parameters were voltage of 35 V, current of 150 A, and spray distance of 270 mm. Based on the process optimization, the desired coating was obtained with a microhardness and porosity of 783.62 ± 14.77 HV0.1 and 1.51 ± 0.49%, respectively. Validation tests of the coatings with the optimum conditions agree with the values predicted by the model. The microstructure, tensile bonding strength and wear tests of the optimized coatings were characterized. The Fe-based coating had a bonding strength of 40.8 ± 1.4 MPa. The wear rate of the coating was 12.26 × 10−6 mm3/Nm, which was about 2.4 times lower than that of the 65Mn steel substrate. [ABSTRACT FROM AUTHOR]

The clinical significance of hsa_circ_0004018 and hsa_circ_0003570 in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) is unclear. We aimed to explore the clinical significance and prognostic utility of these two circular RNAs (circRNAs) in patients with HBV-HCC. Based on 86 paired tissue samples of HCC and adjacent non-HCC, the relative expression profiles of hsa_circ_0004018 and hsa_circ_0003570 were determined using quantitative real-time polymerase chain reactions. The cut-off values were the median expression of each of the two circRNAs in 86 patients with HBV-HCC. The combination group comprised patients with high levels of the two circRNAs. Clinicopathological features, body composition profiles at the L3 level, and survival rates were investigated. The expression of hsa_circ_0004018 and hsa_circ_0003570 was downregulated in HCC tissues compared with non-HCC tissues. High expression levels of hsa_circ_0003570 (hazard ratio (HR), 0.437; p = 0.009) and hsa_circ_0004018 (HR, 0.435; p = 0.005) were inversely independent risk factors for overall and progression-free survival in patients with HBV-HCC, whereas the combination group was also an inversely independent risk factor for overall (HR, 0.399; p = 0.005) and progression-free survival (HR, 0.422; p = 0.003) in patients with HBV-HCC. The combination of hsa_circ_0003570 and hsa_circ_0004018 may be a potential prognostic biomarker for HBV-HCC. [ABSTRACT FROM AUTHOR]

All eukaryotic cells, including oocytes, utilize an engine called cyclin-dependent kinase (Cdk) to drive the cell cycle. Cdks are activated by a co-factor called cyclin, which regulates their activity. The key Cdk–cyclin complex that regulates the oocyte cell cycle is known as Cdk1–cyclin B1. Recent studies have elucidated the roles of other cyclins, such as B2, B3, A2, and O, in oocyte cell cycle regulation. This review aims to discuss the recently discovered roles of various cyclins in mouse oocyte cell cycle regulation in accordance with the sequential progression of the cell cycle. In addition, this review addresses the translation and degradation of cyclins to modulate the activity of Cdks. Overall, the literature indicates that each cyclin performs unique and redundant functions at various stages of the cell cycle, while their expression and degradation are tightly regulated. Taken together, this review provides new insights into the regulatory role and function of cyclins in oocyte cell cycle progression. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Y exercise is a therapeutic exercise facilitating lower trapezius muscle activity. OBJECTIVE: To identify the effects of scapular movement cues (posterior tilt vs. posterior tilt with adduction/depression) on trapezius muscle activity during Y exercise. METHODS: Fifteen healthy men without current shoulder pain performed general Y exercise; Y exercise with cues for scapular posterior tilt; and Y exercise with cues for scapular posterior tilt, adduction, and depression. Electromyography (EMG) data for the trapezius muscles were collected during Y exercise. The posterior tilt angle of the scapula was measured in the prone position with and without cues for scapular posterior tilt using an inclinometer application. RESULTS: The greatest lower trapezius muscle activity was observed during Y exercise with cues for scapular posterior tilt, while the greatest EMG activity of the upper trapezius was observed during Y exercise with cues for scapular posterior tilt, adduction, and depression (p < 0.05). Middle trapezius muscle activity did not significantly differ among the three Y exercise conditions (p = 0.175). Cues for scapular posterior tilt significantly increased the scapular posterior tilt angle in the prone shoulder abduction position (p = 0.007). CONCLUSION: Cues for scapular posterior tilt were most effective in facilitating lower trapezius muscle activity during Y exercise. [ABSTRACT FROM AUTHOR]

Background: Lumbar foraminal stenosis (LFS) is an important pathologic entity that causes lumbar radiculopathies. Unrecognized LFS may be associated with surgical failure, and LFS remains challenging to treat surgically. This retrospective cohort study aimed to evaluate the clinical outcomes and prognostic factors of decompressive foraminotomy performed using the biportal endoscopic paraspinal approach for LFS. Methods: A total of 102 consecutive patients with single-level unilateral LFS who underwent biportal endoscopic paraspinal decompressive foraminotomy were included. We evaluated the Visual Analogue Scale (VAS) score and the Oswestry Disability Index (ODI) before and after surgery. Demographic, preoperative data, and radiologic parameters, including the coronal root angle (CRA), were investigated. The patients were divided into Group A (satisfaction group) and Group B (unsatisfaction group). Parameters were compared between these two groups to identify the factors influencing unsatisfactory outcomes. Results: In Group A (78.8% of patients), VAS and ODI scores significantly improved after biportal endoscopic paraspinal decompressive foraminotomy (p < 0.001). However, Group B (21.2% of patients) showed higher incidences of stenosis at the lower lumbar level (p = 0.009), wide segmental lordosis (p = 0.021), and narrow ipsilateral CRA (p = 0.009). In the logistic regression analysis, lower lumbar level (OR = 13.82, 95% CI: 1.33–143.48, p = 0.028) and narrow ipsilateral CRA (OR = 0.92, 95% CI: 0.86–1.00, p = 0.047) were associated with unsatisfactory outcomes. Conclusions: Significant improvement in clinical outcomes was observed for a year after biportal endoscopic paraspinal decompressive foraminotomy. However, clinical outcomes were unsatisfactory in 21.2% of patients, and lower lumbar level and narrow ipsilateral CRA were independent risk factors for unsatisfactory outcomes. [ABSTRACT FROM AUTHOR]

We investigate the role strain-induced deoxygenation plays on the observed T c attenuation in multilayers of La 1/3 Ca 1/3 MnO 3 (LCMO) and YBa 2 Cu 3 O 7- δ (YBCO), where a long-range ferromagnetic/superconductor proximity effect is proposed to exist. We compare changes to the superconducting T c in several sets of oxygen-underdoped perovskite/YBCO/perovskite trilayers, where the perovskite layers consist of LCMO; LaNiO 3 (LNO), which is structurally similar to LCMO but non-magnetic; and PrBa 2 Cu 3 O 7- δ (PBCO), which is both non-magnetic and better lattice-matched with YBCO. We find that LCMO and LNO trilayers show similar T c attenuation in response to decreasing annealing pressure. We also use x-ray absorption spectroscopy to directly gauge the hole concentration (p) in LCMO trilayers, where we find both thinner YBCO layers and greater oxygen underdoping decreases p. Our results indicate that strain-induced deoxygenation of the YBCO layer by itself can account for the observed T c attenuation in LCMO/YBCO multilayers. [ABSTRACT FROM AUTHOR]

This study aimed to investigate differences in prefrontal cortex activation between older adults with and without depressive symptoms during cognitive tasks using functional near-infrared spectroscopy (fNIRS). We examined 204 older participants without psychiatric or neurological disorders who completed the Geriatric Depression Scale, digit span, Verbal Fluency Test, and Stroop test. At the same time, prefrontal cortex activation was recorded using fNIRS. During the Stroop test, significantly reduced hemodynamics were observed in the depressive-symptom group. The mean accΔHbO2 of all channel averages was 0.14 μM in the control group and −0.75 μM in the depressive-symptom group (p = 0.03). The right hemisphere average was 0.13 μM and −0.96 μM, respectively (p = 0.02), and the left hemisphere average was 0.14 μM and −0.54 μM, respectively (p = 0.12). There was no significant difference in hemodynamic response (mean accΔHbO2) between the two groups during the digit span backward and VFT. In conclusion, reduced hemodynamics in the frontal cortex of the depressive-symptom group has been observed. The frontal fNIRS signal and the Stroop task may be used to measure depressive symptoms sensitively in the elderly. [ABSTRACT FROM AUTHOR]

Age‐associated immune changes and pre‐existing influenza immunity are hypothesized to reduce influenza vaccine effectiveness in older adults, although the contribution of each factor is unknown. Here, we constructed influenza‐specific IgG landscapes and determined baseline concentrations of cytokines typically associated with chronic inflammation in older adults (TNF‐α, IL‐10, IL‐6, and IFN‐γ) in 30 high and 29 low influenza vaccine responders (HR and LR, respectively). In a background of high H3 antibody titers, vaccine‐specific H3, but not H1, antibody titers were boosted in LRs to titers comparable to HRs. Pre‐vaccination concentrations of IL‐10 were higher in LRs compared with HRs and inversely correlated with titers of pre‐existing influenza antibodies. Baseline TNF‐α concentrations were positively correlated with fold‐increases in antibody titers in HRs. Our findings indicate that baseline inflammatory status is an important determinant for generating post‐vaccination hemagglutinin‐inhibition antibodies in older adults, and IgG responses can be boosted in the context of high pre‐existing immunity. [ABSTRACT FROM AUTHOR]

Simple Summary: CTHRC1 is a protein with pro-tumoral effects that is highly expressed in tumors. We found that cancer stroma is the major source of CTHRC1 secretion in pancreatic cancer, and CTHRC1 regulates cancer extracellular matrix (ECM) remodeling by activating pancreatic stellate cells (PSCs), a main component of pancreatic cancer stroma. Our results show that CTHRC1-activated PSCs differentiated into myofibroblast-like CAFs (myCAFs). Moreover, the pro-tumoral effects manifested by CTHRC1 were more potent through PSC activation than via autocrine action. Periostin, a stroma-specific molecule, demonstrated an essential role in the CTHRC1–PSCs–cancer metastasis axis. Blocking CTHRC1 reversed PSC activation in vitro and showed significant anti-tumoral effects in animal models. However, long-term CTHRC1 treatment likely caused a shift from myCAFs into inflammatory CAFs. This study elucidates PSC activation as the central mechanism underlying the pro-tumoral effects of CTHRC1 and suggests that future studies on CTHRC1 as a potential therapeutic target for pancreatic cancer are warranted. [BACKGROUND] Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein that contributes to the progression of various cancers, including pancreatic cancer. The higher expression of CTHRC1 in tumor tissues is associated with poorer survival outcomes. However, its specific roles in tumor extracellular matrix (ECM) remodeling remain unclear. Our study aims to investigate the influences of CTHRC1 on pancreatic stellate cells (PSCs), a main source of ECM production in pancreatic cancer. [METHODS AND RESULTS] The analyses of the publicly available pancreatic cancer patient data revealed that CTHRC1 is mainly expressed in cancer stroma and highly correlated with ECM-related genes. An in vitro study showed that more than 40% of these genes can be upregulated by CTHRC1. CTHRC1 specifically activated PSC into myofibroblast-like cancer-associated fibroblasts (myCAFs), which are characterized by a significantly upregulated POSTN gene expression. Periostin (coded by the POSTN gene) has a central role in the CTHRC1–PSCs–cancer metastasis axis. Furthermore, CTHRC1 promoted pancreatic cancer cell proliferation through PSC activation to a greater extent than via direct stimulation. Proof-of-concept experiments showed that the long-term (4-week) inhibition of CTHRC1 led to significant tumor suppression and ECM reduction, and also resulted in an unexpected shift in the CAF subtype from myCAFs to inflammatory CAFs (iCAFs). [CONCLUSION] PSC activation was demonstrated to be the key molecular mechanism responsible for the tumor-promoting effects of CTHRC1, and CTHRC1 has a critical role in CAF subtype differentiation and tumor microenvironment (TME) remodeling. The inhibition of CTHRC1 as a therapeutic strategy for the treatment of pancreatic cancer warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted total knee arthroplasty (r-TKA) can reportedly achieve more accurate implant positioning than conventional total knee arthroplasty (c-TKA), although its learning curve is controversial. Moreover, few studies have investigated r-TKA in Asians, who have different anatomical characteristics. This study aimed to determine the learning curve for r-TKA and compare implant positions between r-TKA and c-TKA according to the learning curve in Asian patients. Methods: This prospective study included 50 consecutive c-TKAs (group C), followed by 50 consecutive r-TKAs conducted using the MAKO robotic system (Stryker, USA). Cumulative summation analyses were performed to assess the learning curve for operative time in r-TKA. Accordingly, the r-TKA cases were divided into the initial (group I) and proficiency cases (group P). The femoral and tibial component positions in the coronal, sagittal, and axial planes and lower limb alignment were compared among the three groups. Results: r-TKA was associated with a learning curve for operative time in 18 cases. The operative time was significantly shorter in groups C and P than that in group I, with no significant difference between groups C and P. Groups I and P demonstrated fewer outliers with respect to lower limb alignment, femoral component coronal position, axial position, and tibial component sagittal position than those in group C, with no significant difference between groups I and P. Conclusion: The operative time did not differ significantly between r-TKA and c-TKA after the learning curve. Surgeons could expect more accurate and reproducible lower limb alignment and implant positioning with r-TKA in Asian patients, irrespective of the learning curve. [ABSTRACT FROM AUTHOR]

Mineralization is one of the important indexes to evaluate bone repair performance of bone repair materials. The rapid deposition and uniform distribution of mineral coating have always been a research focus of biomineralized membrane materials. Here, poly (ε-caprolactone) (PCL) nanofibers with shish-kebab (SK) structure biomimetic the surface features of collagen fibrils in bone tissue were created by electrospinning technology and self-induced crystallization methods. Biomimetic mineralization method was used to fabricate mineralized PCL nanofibrous membranes. SK structure increased the specific surface area of PCL nanofibrous membranes and provided more nucleation sites to promote mineralization and crystallization of calcium phosphate (CaP) mineralized layer, and mineralized PCL nanofibrous membrane significantly enhanced cell proliferation, attachment and ALP activity. SK structure and CaP coating synergistically promoted cell proliferation and osteoinductive ability of PCL nanofibrous membrane which had potential application value in the field of bone repair materials. [ABSTRACT FROM AUTHOR]

Objective: Posttraumatic stress disorder (PTSD) is characterized by increased inflammatory processing and altered brain volume. In this study, we investigated the relationship between inflammatory markers and brain volume in patients with PTSD. Methods: Forty-five patients with PTSD, and 70 healthy controls (HC) completed clinical assessments and self-reported psychopathology scales. Factors associated with inflammatory responses including brain-derived neurotrophic factor and four inflammatory biomarkers (C-reactive protein, cortisol, Interleukin-6, and homocysteine) and T1-magnetic resonance imaging of the brain were measured. Results: In the PTSD group, cortisol level was significantly lower (t = 2.438, p = 0.046) than that of the HC. Cortisol level was significantly negatively correlated with the left thalamus proper (r = -0.369, p = 0.035), right thalamus proper (r = -0.394, p = 0.014), right frontal pole (r = -0.348, p = 0.039), left occipital pole (r = -0.338, p = 0.044), and right superior occipital gyrus (r = -0.397, p = 0.008) in patients with PTSD. However, these significant correlations were not observed in HC. Conclusion: Our results indicate that increased cortisol level, even though its average level was lower than that of HC, is associated with smaller volumes of the thalamus, right frontal pole, left occipital pole, and right superior occipital gyrus in patients with PTSD. Cortisol, a major stress hormone, might be a reliable biomarker to brain volumes and pathophysiological pathways in patients with PTSD. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The impacts of elevated troponin I levels after coronary artery bypass grafting (CABG) on long-term outcomes were investigated. METHODS A total of 996 patients who underwent elective isolated CABG for stable or unstable angina were enrolled. Patients were divided into higher and lower groups based on 80th percentile postoperative peak troponin I (ppTnI) levels. The relationship between ppTnI and long-term clinical outcomes was analysed. RESULTS The median ppTnI was 1.55 (2.74) ng/ml and was significantly higher in the conventional CABG subgroup than in the beating-heart CABG subgroup: 4.04 (4.71) vs 1.24 (1.99) ng/ml, P  <   0.001. The 80th percentile of ppTnI was 3.3 ng/ml in the beating-heart CABG subgroup and 8.9 ng/ml in the conventional CABG subgroup. In the conventional CABG subgroup (n  = 150), 10-year overall survival showed no significant difference between the higher (≥8.9 ng/ml) and lower (<8.9 ng/ml) ppTnI groups: 71% (10%) vs 76% (5%), P  =   0.316. However, the beating-heart CABG subgroup (n  = 846) showed significantly worse 10-year overall survival in the higher ppTnI group (≥3.3 ng/ml) than in the lower ppTnI group (<3.3 ng/ml): 64% (6%) vs 73% (3%), P  =   0.010. In the beating-heart CABG subgroup, multivariable analysis showed that ppTnI exceeding the 80th percentile was a risk factor for overall death (hazard ratio: 1.505, 95% confidence interval: 1.019–2.225, P  =   0.040). CONCLUSIONS Higher ppTnI over the 80th percentile was associated with worse long-term survival in beating-heart CABG, but not in conventional CABG. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted total knee arthroplasty (r-TKA) can reportedly achieve more accurate implant positioning than conventional total knee arthroplasty (c-TKA), although its learning curve is controversial. Moreover, few studies have investigated r-TKA in Asians, who have different anatomical characteristics. This study aimed to determine the learning curve for r-TKA and compare implant positions between r-TKA and c-TKA according to the learning curve in Asian patients. Methods: This prospective study included 50 consecutive c-TKAs (group C), followed by 50 consecutive r-TKAs conducted using the MAKO robotic system (Stryker, USA). Cumulative summation analyses were performed to assess the learning curve for operative time in r-TKA. Accordingly, the r-TKA cases were divided into the initial (group I) and proficiency cases (group P). The femoral and tibial component positions in the coronal, sagittal, and axial planes and lower limb alignment were compared among the three groups. Results: r-TKA was associated with a learning curve for operative time in 18 cases. The operative time was significantly shorter in groups C and P than that in group I, with no significant difference between groups C and P. Groups I and P demonstrated fewer outliers with respect to lower limb alignment, femoral component coronal position, axial position, and tibial component sagittal position than those in group C, with no significant difference between groups I and P. Conclusion: The operative time did not differ significantly between r-TKA and c-TKA after the learning curve. Surgeons could expect more accurate and reproducible lower limb alignment and implant positioning with r-TKA in Asian patients, irrespective of the learning curve. [ABSTRACT FROM AUTHOR]

(Z)-5-Benzylidene-2-phenylthiazol-4(5H)-one ((Z)-BPT) derivatives were designed by combining the structural characteristics of two tyrosinase inhibitors. The double-bond geometry of trisubstituted alkenes, (Z)-BPTs 1–14, was determined based on the 3JC,Hβ coupling constant of 1H-coupled 13C NMR spectra. Three (Z)-BPT derivatives (1–3) showed stronger tyrosinase inhibitory activities than kojic acid; in particular, 2 was to be 189-fold more potent than kojic acid. Kinetic analysis using mushroom tyrosinase indicated that 1 and 2 were competitive inhibitors, whereas 3 was a mixed-type inhibitor. The in silico results revealed that 1–3 could strongly bind to the active sites of mushroom and human tyrosinases, supporting the kinetic results. Derivatives 1 and 2 decreased the intracellular melanin contents in a concentration-dependent manner in B16F10 cells, and their anti-melanogenic efficacy exceeded that of kojic acid. The anti-tyrosinase activity of 1 and 2 in B16F10 cells was similar to their anti-melanogenic effects, suggesting that their anti-melanogenic effects were primarily owing to their anti-tyrosinase activity. Western blotting of B16F10 cells revealed that the derivatives 1 and 2 inhibited tyrosinase expression, which partially contributes to their anti-melanogenic ability. Several derivatives, including 2 and 3, exhibited potent antioxidant activities against ABTS cation radicals, DPPH radicals, ROS, and peroxynitrite. These results suggest that (Z)-BPT derivatives 1 and 2 have promising potential as novel anti-melanogenic agents. [ABSTRACT FROM AUTHOR]

This study aimed to investigate functional brain connectivity in patients with end-stage renal disease (ESRD) undergoing hemodialysis using functional near-infrared spectroscopy (fNIRS) and to analyze the effect of hemodialysis on functional brain connectivity. We prospectively enrolled patients with ESRD undergoing hemodialysis for > 6 months without any history of neurological or psychiatric disorders. fNIRS data were acquired using a NIRSIT Lite device. Measurements were performed thrice in the resting state for each patient: before the start of hemodialysis (pre-HD), 1 h after the start of hemodialysis (mid-HD), and after the end of hemodialysis (post-HD). We processed and exported all data, and created a weighted connectivity matrix using Pearson correlation analysis. We obtained functional connectivity measures from the connectivity matrix by applying a graph theoretical analysis. We then compared differences in functional connectivity measures according to hemodialysis status in patients with ESRD. We included 34 patients with ESRD. There were significant changes in the mean clustering coefficient, transitivity, and assortative coefficient between the pre- and post-HD periods (0.353 vs. 0.399, p = 0.047; 0.523 vs. 0.600, p = 0.042; and 0.043 vs. − 0.012, p = 0.044, respectively). However, there were no changes in the mean clustering coefficient, transitivity, and assortative coefficient between the pre- and mid-HD periods, or between the mid- and post-HD periods. In addition, there were no significant differences in the average strength, global efficiency, and local efficiency among the pre-, mid-, and post-HD periods. We demonstrated a significant effect of hemodialysis on functional brain connectivity in patients with ESRD. Functional brain connectivity changes more efficiently during hemodialysis. [ABSTRACT FROM AUTHOR]

Aim: The incidence of fungal sinusitis is increasing; however, its pathophysiology has not been investigated previously. We investigate the effect of periodontitis on the incidence of fungal sinusitis over a 12‐year follow‐up period using nationwide population‐based data. Materials and Methods: The periodontitis group was randomly selected from the National Health Insurance Service database. The non‐periodontitis group was obtained by propensity score matching considering several variables. The primary end point was the diagnosis of sinonasal fungal balls (SFBs) and invasive fungal sinusitis (IFS). Results: The periodontitis and non‐periodontitis groups included 12,442 and 12,442 individuals, respectively. The overall adjusted hazard ratio (aHR) for SFBs in the periodontitis group was 1.46 (p =.002). In subgroup analysis, the aHR for SFBs was 1.59 (p = 0.008) for those with underlying chronic kidney disease (CKD), 1.58 (p =.022) for those with underlying atopic dermatitis, 1.48 (p =.019) for those with chronic obstructive pulmonary disease (COPD), and 1.36 (p =.030) for those with diabetes mellitus (DM), but these values are applicable only when considering the relationship between periodontitis and SFB. The aHR for IFS in the periodontitis group was higher than in the non‐periodontitis group (2.80; p =.004). Conclusions: The risk of SFBs and IFS increased after diagnosis of periodontitis. This trend is often more severe in patients with DM, COPD, or CKD, but this association with underlying diseases is applicable only when considering the association between periodontitis and fungal sinusitis. [ABSTRACT FROM AUTHOR]

We aimed to investigate the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with primary restless legs syndrome (RLS) compared to healthy controls. Seventy-one patients with primary RLS and 55 healthy controls were recruited. They underwent brain MRI using a three-tesla MRI scanner, including three-dimensional T1-weighted images. The intrinsic thalamic network was determined using graph theoretical analysis. The right and left whole thalamic volumes, and the right pulvinar inferior, left ventral posterolateral, left medial ventral, and left pulvinar inferior nuclei volumes in the patients with RLS were lower than those in healthy controls (0.433 vs. 0.447%, p = 0.034; 0.482 vs. 0.502%, p = 0.016; 0.013 vs. 0.015%, p = 0.031; 0.062 vs. 0.065%, p = 0.035; 0.001 vs. 0.001%, p = 0.034; 0.018 vs. 0.020%, p = 0.043; respectively). There was also a difference in the intrinsic thalamic network between the groups. The assortative coefficient in patients with RLS was higher than that in healthy controls (0.0318 vs. − 0.0358, p = 0.048). We demonstrated the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with RLS compared to healthy controls. These changes might be related to RLS pathophysiology and suggest the pivotal role of the thalamus in RLS symptoms. [ABSTRACT FROM AUTHOR]