bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering Parkinson’s Disease through Eye Movements: A Promising Tool for Early Diagnosis in the Face of Cognitive Impairment
Authors: Liao Xianglian , Yao Jian , Tang Hongyin , Xing Yilan , Zhao Xin , Nie Daao , Luan Ping , Li Guihua
Published: June 2024

Cognitive dysfunction is the most common and important nonmotor symptom in Parkinson’s disease (PD) and can occur at any stage. However, there is still a lack of effective biomarkers to evaluate the decline in cognitive function and predict the progression of the disease, especially in the early stage. At present, the cognitive scale is widely used to evaluate the cognitive function of patients with PD, but its sensitivity and accuracy are relatively limited, especially in the early identification of mild cognitive impairment. Eye movement tracking is an advanced neurophysiological measurement method that serves as a powerful means to study the relationship between behavior and neural mechanisms. In recent years, eye movement tracking has been found to provide a nonverbal and less cognitive method to measure the disease progress of patients with cognitive impairment. Moreover, there is a good correlation between eye movement tracking and the traditional cognitive assessment scale, indicating that eye movement tracking can be used to evaluate and monitor the cognitive status, disease severity, and disease progression of patients with PD. Compared to the traditional cognitive scale, the eye movement detected by the instrument has better objectivity and repeatability. Existing studies have found that executive dysfunction is one of the most important manifestations of cognitive dysfunction in patients with PD and is related to an increase in the error rate of the saccade, an increase in the disinhibition of the delayed saccade task, and a prolongation of the saccade reaction time. This suggests that eye movement measurement plays an important role in the early diagnosis, progression, and differential diagnosis of PD and may even help to predict the disease progression of patients with PD and cognitive impairment. In this article, we review the correlation between cognitive impairment and eye movement disorder in patients with PD.
Atrial Fibrillation Termination as a Predictor for Persistent Atrial Fibrillation Ablation: A Systemic Review and Meta‐Analysis of Prospective Studies
Authors: He Jialing , Zhang Zhen , Luo Duan , Yang Xianchen , Yang Guoshu , Liu Hanxiong
Published: June 2024

Background: In this systematic review and meta‐analysis, we aimed to validate the predictive role of atrial fibrillation (AF) termination in long‐term arrhythmia recurrence.

Method: Our search encompassed databases including MEDLINE, EMBASE, PubMed, and the Cochrane Library up to August 1, 2021. Three independent reviewers conducted screening and data extraction. The data included ablation strategy, recurrence mode, AF termination mode, numbers of patients, and recurrence cases in the termination and nontermination groups. The primary endpoint was the recurrence of atrial arrhythmia at long‐term follow‐up (≥ 12 months).

Results: Our analysis included 22 publications, with 11 prospective studies being eligible for further meta‐analysis. Among these, 14 studies reported significantly lower rates of arrhythmia recurrence in the AF termination group compared to the nontermination group. Among seven studies involving 1114 patients that examined single procedure outcomes, the pooled estimated effect was RR 0.78 (95% CI 0.68–1.90) with an I2 value of 57%. Subgroup analysis focusing on termination mode as sinus rhythm yielded a pooled estimated effect of RR 0.74 (95% CI 0.59–0.92) with an I2 value of 47%. Additionally, analysis of seven studies involving 1433 patients for repeat procedures demonstrated a significant preference for the AF termination group (RR 0.83, 95% CI 0.71–0.97, I2 = 84%). Subgroup analysis indicated reduced heterogeneity when the termination mode was sinus rhythm (RR 0.68, 95% CI 0.51–0.90, I2 = 57%).

Conclusion: Our study establishes that AF termination serves as an effective predictor for the success of persistent AF ablation procedures. This finding holds potential implications for clinical practice and contributes to our understanding of long‐term arrhythmia recurrence in the context of AF termination.
Supplementary Table 5 from Reshaping the Tumor Microenvironment of KRASG12D Pancreatic Ductal Adenocarcinoma with Combined SOS1 and MEK Inhibition for Improved Immunotherapy Response
Authors: Norgard Robert J. , Budhani Pratha , O'Brien Sarah A. , Xia Youli , Egan Jessica N. , Flynn Brianna , Tagore Joshua R. , Seco Joseph , Peet Gregory W. , Mikucka Ania , Wasti Ruby , Chan Li-Chuan , Hinkel Melanie , Martinez-Morilla Sandra , Pignatelli Jeanine , Trapani Francesca , Corse Emily , Feng Di , Kostyrko Kaja , Hofmann Marco H. , Liu Kang , Kashyap Abhishek S.
Published: June 2024

Supplementary Table 5
FIGURE 5 from Reshaping the Tumor Microenvironment of KRASG12D Pancreatic Ductal Adenocarcinoma with Combined SOS1 and MEK Inhibition for Improved Immunotherapy Response
Authors: Norgard Robert J. , Budhani Pratha , O'Brien Sarah A. , Xia Youli , Egan Jessica N. , Flynn Brianna , Tagore Joshua R. , Seco Joseph , Peet Gregory W. , Mikucka Ania , Wasti Ruby , Chan Li-Chuan , Hinkel Melanie , Martinez-Morilla Sandra , Pignatelli Jeanine , Trapani Francesca , Corse Emily , Feng Di , Kostyrko Kaja , Hofmann Marco H. , Liu Kang , Kashyap Abhishek S.
Published: June 2024

Combination of SOS1i+MEKi inhibitors sensitize cold KPCY tumors to confer prolonged TGI and immune memory. A, Schematic of treatment regimen of SOS1i+MEKi with aPD-1, aCTLA-4, and aCD40. B, Tumor volume from day postimplantation. T cell low clone (TC4) were implanted subcutaneously into C57Bl/6 mice (n = 10–11 mice per group) and treated when tumors reached 40–100 mm3. C, Waterfall plots from mice bearing tumors comparing start of therapy (day 12) with 48 hours after final dose (day 23; n = 10–11 mice per group). D, Table summarizing results of outcomes after treatment of TGI at day 23, tumor regressions at day 23, complete responders at day 23, tumor regressions at end of experiment day 60, and complete responders at end of experiment day 60. Columns are in order of B. E, Kaplan–Meier survival curves from mice implanted with TC4 clone and treated with indicated therapy. Median survival in days shown in parenthesis. n = 10–11 mice per group (* = 0.05, ** = 0.01, *** = 0.001). F, Survival of mice cured by SOS1i+MEKi+aPD-1+aCTLA-4+aCD40 therapy in B were rechallenged with a secondary tumor on the opposing flank. Kaplan–Meier survival curves of cured mice (n = 3) or age-matched controls (n = 5).
Long-Term Renal Function with Cardiac Contractility Modulation Therapy
Authors: Yuecel Goekhan , Yazdani Babak , Schreiner Kristin , Fastner Christian , Hetjens Svetlana , Husain-Syed Faeq , Kruska Mathieu , Duerschmied Daniel , Krämer Bernhard K. , Abraham William T. , Akin Ibrahim , Kuschyk Juergen
Published: June 2024

Background: Cardiac implantable electrical devices are able to affect kidney function through hemodynamic improvements. The Cardiac Contractility Modulation (CCM) is a device-based therapy option for patients with symptomatic chronic heart failure (HF) despite optimized medical treatment. The long-term cardiorenal interactions for CCM treated patients are yet to be described.
Methods: CCM recipients (n=187) from the Mannheim Cardiac Contractility Modulation Observational Study (MAINTAINED) were evaluated in the long-term (up to 60 months) for changes in serum creatinine, estimated glomerular filtration rate (eGFR), other surrogate markers of kidney function, and the chronic kidney disease (CKD) stage-distribution. With regard to kidney function at baseline, the patients were furthermore grouped to either advanced CKD (aCKD, CKD-stage ≥3, eGFR≤59mL/min/1.73 m2, n=107) or preserved kidney function and mild CKD (pCKD, CKD stages 1-2, eGFR≥60mL/min/1.73 m2, n=80). The groups were compared for differences regarding kidney function, New York Heart Association classification (NYHA), biventricular systolic function, HF hospitalizations and other parameters in the long-term (60 months).
Results: CKD stage distribution remained stable during the entire follow-up (p=0.65). An increase in serum creatinine (1.47±1 vs. 1.6±1mg/dL) with a corresponding decline of eGFR (58.2±23.4 vs. 54.2±24.4mL/min/1.73 m2, both p<.05) were seen after 60 months but not before for the total cohort, which was only significant in pCKD patients in terms of group comparison. Mean survival (54.3±1.3 vs. 55.3±1.2months, p=0.53) was comparable in both groups. Improvements in NYHA (3.11±0.46 vs. 2.94±0.41 to 2.28±0.8 vs. 1.94±0.6) and LVEF (24.8±7.1 vs. 22.9±6.6 to 31.1±11.4 vs. 35.5±11.1%) were likewise similar after 60 months (both p <.05). The aCKD patients suffered from more HF-hospitalizations and ventricular tachycardias during the entire follow-up period (both p<.05).
Conclusions: The kidney function parameters and CKD stage distribution might remain stable in CCM treated HF patients in the long-term, who experience improvements in LVEF and functional status, regardless of their kidney function before. An impaired kidney function might be associated with further cardiovascular comorbidities and more advanced HF before CCM, and could be an additional risk factor of HF complications afterwards.
Prevention of Inflammatory Disorders in the Preterm Neonate: An Update with a Special Focus on Bronchopulmonary Dysplasia
Authors: Glaser Kirsten , Jensen Erik A. , Wright Clyde J.
Published: June 2024

Background: The rates of major neonatal morbidities, such as bronchopulmonary dysplasia, necrotizing enterocolitis, preterm white matter disease, and retinopathy of prematurity, remain high among surviving preterm infants. Exposure to inflammatory stimuli and the subsequent host innate immune response contribute to the risk of developing these complications of prematurity. Notably, the burden of inflammation and associated neonatal morbidity is inversely related to gestational age – leaving primarily but not exclusively the tiniest babies at highest risk. Summary: Avoidance, prevention, and treatment of inflammation to reduce this burden remain a major goal for neonatologists worldwide. In this review, we discuss the link between the host response to inflammatory stimuli and the disease state. We argue that inflammatory exposures play a key role in the pathobiology of preterm birth and that preterm neonates hereafter are highly susceptible to immune stimulation not only from their surrounding environment but also from therapeutic interventions employed in clinical care. Using bronchopulmonary dysplasia as an example, we report clinical studies demonstrating the potential utility of targeting inflammation to prevent this neonatal morbidity. On the contrary, we highlight limitations in our current understanding of how inflammation contributes to disease prevention and treatment. Key Message: To be successful in preventing and treating inflammation-driven morbidity in neonatal intensive care, it may be necessary to better identify at-risk patients and pair therapeutic interventions to key pathways and mediators of inflammation-associated neonatal morbidity identified in pre-clinical and translational studies.
The Analysis of in vitro Fertilization Outcomes after Fertility-Preserving Therapy for Endometrial Hyperplasia or Carcinoma
Authors: Park JiEun , Yu Eun Jeong , Lee Nara , Park Jae Eun , Seong Seok Ju , Lee Woo Sik , Lee Hee Jun
Published: June 2024

Objectives: This study aimed to evaluate the clinical efficacy of fertility-preserving therapy through in vitro fertilization (IVF) procedures in women who were pathologically diagnosed with endometrial hyperplasia or carcinoma. Design: A retrospective cohort study on fertility-preserving therapy was conducted. Participants/Materials, Setting: A total of 82 women were enrolled who had simple endometrial hyperplasia (SH), complex hyperplasia (CH), complex atypical hyperplasia (CAH), and endometrioid endometrial carcinoma stage IA (EC IA) and underwent IVF at Gangnam CHA fertility center between January 2008 and December 2020. Methods: The primary endpoints were oncologic outcomes and subsequent reproductive outcomes of patients who underwent fertility-preserving treatments analyzed by χ2 test or Fisher’s exact test. Results: Of the 82 patients, 33 had a cumulative clinical pregnancy (40.2%), and 25 had a cumulative live birth (30.5%) through IVF procedures following pathologic confirmation of complete remission or non-progressive status. The cumulative clinical pregnancy rates and live birth rates for SH were 50.0% and 30.0%, for CH were 37.8% and 28.9%, for CAH were 25.0% and 25.0%, and for EC were 38.5% and 38.5%, respectively. There were no significant differences in cumulative clinical pregnancy rates or live birth rates when comparing the four groups. There was a difference in endometrial thickness between medroxyprogesterone acetate (MPA) treatment group and intrauterine device (IUD) group (p = 0.036); however, there were no significant differences in clinical pregnancy rates among MPA, IUD, and MPA+IUD groups. Limitations: Because of the retrospective nature of the study, many factors relevant to the treatment decision were not strictly controlled. Conclusions: All endometrial hyperplasia and carcinoma groups had competent cumulative live birth rates by IVF procedures. There may be differences in endometrial thickness depending on the treatment methods, but this does not affect clinical pregnancy rates. Therefore, the fertility-preserving treatment for endometrial hyperplasia and carcinoma is a safe and feasible method that results in good IVF outcomes.
Mapping of Capsular Side Effects by using Intraoperative Motor-Evoked Potentials during Asleep Deep Brain Stimulation Surgery of the Subthalamic Nucleus for Parkinson’s Disease
Authors: Karazapryanov Petar Antoan , Gabrovski Kaloyan Rumenov , Milenova Yoana , Pavlov Velislav Kirilov , Karameshev Alexander , Damianova Maria , Sirakov Stanimir , Minkin Krasimir
Published: June 2024

Introduction: The aim of this study was to present a novel technique for subthalamic nucleus (STN) deep brain stimulation (DBS) implantation under general anesthesia by using intraoperative motor-evoked potentials (MEPs) through direct lead stimulation and determining their correlation to the thresholds of postoperative stimulation-induced side effects. Methods: This study included 22 consecutive patients with advanced Parkinson’s disease who underwent surgery in our institution between January 2021 and September 2023. All patients underwent bilateral implantation in the STN (44 leads) under general anesthesia without microelectrode recordings (MERs) by using MEPs with electrostimulation directly through the DBS lead. No cortical stimulation was performed during this process. Intraoperative fluoroscopic guidance and immediate postoperative computed tomography were used to verify the electrode’s position. The lowest MEP thresholds were recorded and were correlated to the postoperative stimulation-induced side-effect threshold. The predictive values of the MEPs were analyzed. Five DBS leads were repositioned intraoperatively due to the MEP results. Results: A moderately strong positive correlation was found between the MEP threshold and the capsular side-effect threshold (RS = 0.425, 95% CI, 0.17–0.67, p = 0.004). The highest sensitivity and specificity for predicting a side-effect threshold of 5 mA were found to be at 2.4 mA MEP threshold (sensitivity 97%, specificity 87.5%, positive predictive value 97%, and negative predictive value 87.5%). We also found high sensitivity and specificity (100%) at 1.15 mA MEP threshold and 3 mA side-effect threshold. Out of the total 44 leads, 5 (11.3%) leads were repositioned intraoperatively due to MEP thresholds lower than 1 mA (4 leads) or higher than 5 mA (1 lead). The mean accuracy on postoperative CT was 1.05 mm, and there were no postoperative side-effects under 2.8 mA. Conclusion: Intraoperative MEPs with electrostimulation directly through the contacts of the DBS lead correlate with the stimulation-induced capsular side effects. The lead reposition based on intraoperative MEP may enlarge the therapeutic window of DBS stimulation.
Effects of Dapagliflozin in Patients with Membranous Nephropathy
Authors: Chertow Glenn M. , Heerspink Hiddo Lambers , Mark Patrick B. , Dwyer Jamie P. , Nowicki Michal , Wheeler David C. , Correa-Rotter Ricardo , Rossing Peter , Toto Robert D. , Langkilde Anna Maria , Jongs Niels
Published: June 2024

Introduction
Despite the provision of renin-angiotensin-aldosterone-system inhibitors and immunosuppressive therapies, membranous nephropathy often progresses to end-stage kidney disease (ESKD). The objective of this prespecified analysis was to assess the safety and efficacy of dapagliflozin in patients with membranous nephropathy enrolled in the DAPA-CKD trial.

Methods
Patients with an estimated glomerular filtration rate (eGFR) of 25–75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200–5000 mg/g were randomized to dapagliflozin 10 mg once daily or placebo, along with standard-of-care and followed for median 2.4 years. The primary endpoint was a composite of ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Exploratory efficacy endpoints included eGFR slope and UACR.

Results
Among DAPA-CKD participants with membranous nephropathy, 19 were randomized to dapagliflozin and 24 to placebo. Mean (SD) age was 59.9 ± 12.1 years; mean eGFR 45.7 ± 12.1 mL/min/1.73m2, and median UACR 1694.5 (25%, 75% range 891–2582.5) mg/g. Two of 19 (11%) patients randomized to dapagliflozin, and five of 24 (21%) randomized to placebo experienced the primary composite endpoint. Total and chronic mean eGFR slopes for dapagliflozin and placebo were −3.87 and −4.29 and −2.66 and −4.22 mL/min/1.73m2/year, respectively; corresponding between-group mean differences were 0.42 and 1.57 mL/min/1.73m2/year. Dapagliflozin reduced geometric mean (SEM) UACR relative to placebo (−29.3% ± 1.2% versus −3.6% ± 1.1%; between-group mean difference [95% CI] −26.7 [−50.4, 8.3]). Four (21%) patients randomized to dapagliflozin and seven (29%) randomized to placebo experienced a serious adverse event.

Conclusions
In membranous nephropathy, effects of dapagliflozin on kidney disease progression and albuminuria were generally favourable; there was insufficient power to justify formal inference testing.
Plasma Adiponectin Levels in Relation to Chronic Hepatitis B Infection Progression to Liver Cancer Milestones: A Prospective Study
Authors: Chen Chi-Ling , Yang Wei-Shiung , Yang Hwai-I. , Chen Chuen-Fei , Wang Li-Yu , Lu Sheng-Nan , Kao Jia-Horng , Chen Pei-Jer , Chen Chien-Jen
Published: June 2024

Introduction: Our previous nested-case-control study demonstrated elevated adiponectin increased liver cirrhosis and HCC risk in HBV carriers. We extended the analysis to the whole REVEAL-HBV cohort to prospectively evaluate whether adiponectin directly affected end-stage liver diseases, or through affecting HBV progression. Methods: Baseline plasma adiponectin was determined to investigate the association between adiponectin and subsequent HBeAg, HBsAg, and HBV DNA seroclearance, and the development of cirrhosis, HCC and liver-related death. Whether HBV characteristics modify the adiponectin-milestones associations was also examined. Results: Among 3,931 HBsAg(+)/anti-HCV(−) REVEAL-HBV participants, 3,684 had sufficient biosamples left for adiponectin assay. Elevated adiponectin was associated with a higher chance of HBeAg-seropositive, high HBV viral load (≥2 × 105 IU/mL) and high HBsAg titers (≥1,000 IU/mL) in a dose-response manner (OR = 2.25, 95% CI: 1.55–3.28; OR = 2.11, 95% CI: 1.47–3.04; and OR = 1.92, 95% CI: 1.47–2.52 for Q5 vs. Q1, respectively). Those with the highest quintile had a lower chance of achieving HBeAg (HR = 0.48, 95% CI: 0.27–0.85), HBsAg (HR = 0.69, 95% CI: 0.49–0.97), and HBV DNA seroclearance (HR = 0.63, 95% CI: 0.43–0.90) and a higher chance of developing liver cirrhosis (HR = 2.88, 95% CI: 1.98–4.20, HCC (HR = 2.38, 95% CI: 1.52–3.73), and died from liver-related causes (HR = 2.32, 95% CI: 1.51–3.54). HBV genotype significantly modified the adiponectin-HCC (Pinteraction = 0.005) and adiponectin-liver death associations (Pinteraction = 0.0157), with higher risk among genotype C. Conclusion: Elevated adiponectin is consistently associated with all important chronic HBV infection milestones toward progression to liver cancer. The exact mechanism of how adiponectin mediates HBV infection toward carcinogenesis remains unclear and warrants further investigation. Disentangling this may help us in finding new HBV treatment target, biomarker in HBV surveillance to identify high-risk patients, or even cancer prevention.
The Problem with Film: Murayama Tomoyoshi's Variations on the Visible
Authors: Kunigami André Keiji
Published: June 2024

The article explores the film theory written by the Japanese avant-garde artist Murayama Tomoyoshi (1901–1977). Murayama authored a robust yet understudied body of film writing, in the 1920s and 1930s. Although he had a prolific and stable activity related to film—in criticism, theory, screenplays, and even directing—he held an ambivalent opinion about the medium. For him, film could never fulfill art's political task due to what he saw as the ontological restrictions of the medium: its supposedly incorporeal and incessant display of images. However, he kept repeatedly returning to film, based on the fascination with a certain vitality that he saw in the moving image vis-à-vis other types of images such as photography. By reading his film essays in the larger context of his political engagements and his aesthetic theory, the article argues that the contradictions that animated Murayama's “problem with film”—his ambivalent attachment to the medium—reveal his adherences to the racial logics of the Japanese empire and offer a critical perspective on the broader political stakes of cinematic embodiment.
Study on Preventive Intervention of Peri-knee Ecchymosis After Total Knee Replacement
Authors: Hou Dabiao , Tang Yongnan , Huang Chunhua , Wu Wenrui , Zhang Hongyi , Luo Dongbin
Published: June 2024

Objective: To investigate the effectiveness, controllability and safety of fresh plasma infusion in preventing ecchymosis after total knee arthroplasty (TKA). Methods: Patients with osteoarthritis of the knee who received the initial TKA were assigned to study group, control group, and blank control group according to APTT and PT results on the first day postoperatively. Patients in the study group received 400ml fresh frozen plasma infusion on the first day after TKA, and patients in the control group and blank control group received conventional postoperative treatment. The incidence of ecchymosis, the circumference of the affected limb and visual analog scale (VAS) were compared and analyzed in the three groups. Results: 20 patients were included into each group, respectively. After the infusion of fresh frozen plasma, the number of peri-knee ecchymosis in the study group was significantly less than that in the control group on the 7th and 14th days after the operation (P<0.05). On the 14th day after operation, the circumference of the affected limb in the study group was significantly lower than that in the control group (P<0.05), the circumference of the affected limb in the control group was higher than that in the blank control group, and the circumference of the affected limb in the study group was similar to that in the blank control group (P>0.05). On the 7th and 14th day after surgery, the pain degree of the three groups was relieved, and the VAS score of the study group and the blank control group showed no statistically significant difference (P>0.05), while the VAS score of the study group was lower than that of the control group, the difference was statistically significant (P<0.05). Conclusion: For patients with abnormal coagulation function after TKA, timely postoperative infusion of fresh frozen plasma can reduce the incidence of postoperative ecchymosis and relieve pain, which has certain clinical reference significance.
Analysis of rail corrugation deterioration behavior on a heavy-haul railway
Authors: He Jing , Wang Weiqi , Zhang Quan , Wang Wenkun , Yang Nengpu
Published: June 2024

Rail corrugation is a common form of rail damage discovered when servicing heavy-haul railways that seriously affects the safety of wheel–rail systems. To determine the characteristics of the deterioration of a corrugated heavy-haul railway, this study used ABAQUS simulation software to establish a three-dimensional elastic–plastic wheel–rail finite element model. We then simulated the stress and strain distributions of wheel–rail contact spots as C80 freight cars pass through various corrugated sections of heavy-haul railways, featuring different wavelengths and wave depths. The simulation results demonstrated that the stress and strain increase from the peak positions to the troughs, reaching a maximum somewhere behind the troughs, and then decreasing to the next peak. The stress and strain increase as the depth of corrugation increases. The wheel–rail contact exhibits a maximum stress of 1.312 to 1.770 GPa, and the maximum strain is 0.6470% to 0.9897%. Wheel–rail contact stress and strain occur at a maximum of 8–40 mm after the troughs, rather than at the trough position, forming “planing and rolling” effects. This mechanism revealed by the variation in the stress and strain distributions in this study provides a reference for the in-depth analysis of rail corrugation deterioration and for the exploration of the mechanisms of corrugation deterioration of heavy-haul railways.
The Reconstructive Metaverse – Collaboration in Real-Time Shared Mixed Reality Environments for Microsurgical Reconstruction
Authors: Necker Fabian N. , Cholok David J. , Shaheen Mohammed S. , Fischer Marc J. , Gifford Kyle , El Chemaly Trishia , Leuze Christoph W. , Scholz Michael , Daniel Bruce L. , Momeni Arash
Published: June 2024

Plastic surgeons routinely use 3D-models in their clinical practice, from 3D-photography and surface imaging to 3D-segmentations from radiological scans. However, these models continue to be viewed on flattened 2D screens that do not enable an intuitive understanding of 3D-relationships and cause challenges regarding collaboration with colleagues. The Metaverse has been proposed as a new age of applications building on modern Mixed Reality headset technology that allows remote collaboration on virtual 3D-models in a shared physical-virtual space in real-time. We demonstrate the first use of the Metaverse in the context of reconstructive surgery, focusing on preoperative planning discussions and trainee education. Using a HoloLens headset with the Microsoft Mesh application, we performed planning sessions for 4 DIEP-flaps in our reconstructive metaverse on virtual patient-models segmented from routine CT angiography. In these sessions, surgeons discuss perforator anatomy and perforator selection strategies whilst comprehensively assessing the respective models. We demonstrate the workflow for a one-on-one interaction between an attending surgeon and a trainee in a video featuring both viewpoints as seen through the headset. We believe the Metaverse will provide novel opportunities to use the 3D-models that are already created in everyday plastic surgery practice in a more collaborative, immersive, accessible, and educational manner.
Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias
Authors: Kwon Min Chul , Thuring Jan Willem , Querolle Olivier , Dai Xuedong , Verhulst Tinne , Pande Vineet , Marien Ann , Goffin Dries , Wenge Daniela V. , Yue Hong , Cutler Jevon A. , Jin Cyrus , Perner Florian , Hogeling Shanna M. , Shaffer Paul L. , Jacobs Frank , Vinken Petra , Cai Wei , Keersmaekers Vikki , Eyassu Filmon , Bhogal Balpreet , Verstraeten Karin , El Ashkar Sara , Perry Jennifer A. , Jayaguru Prathiba , Barreyro Laura , Kuchnio Anna , Darville Nicolas , Krosky Daniel , Urbanietz Gregor , Verbist Bie , Edwards James P. , Cowley Glenn S. , Kirkpatrick Robert , Steele Ruth , Ferrante Lucille , Guttke Christina , Daskalakis Nikki , Pietsch E. Christine , Wilson David M. , Attar Ricardo , Elsayed Yusri , Fischer Eric S. , Schuringa Jan Jacob , Armstrong Scott A. , Packman Kathryn , Philippar Ulrike
Published: June 2024

The interaction between menin and histone-lysine N-methyltransferase 2A (KMT2A) is a critical dependency for KMT2A- or nucleophosmin 1 (NPM1)–altered leukemias and an emerging opportunity for therapeutic development. JNJ-75276617 (bleximenib) is a novel, orally bioavailable, potent, and selective protein-protein interaction inhibitor of the binding between menin and KMT2A. In KMT2A-rearranged (KMT2A-r) and NPM1-mutant (NPM1c) acute myeloid leukemia (AML) cells, JNJ-75276617 inhibited the association of the menin-KMT2A complex with chromatin at target gene promoters, resulting in reduced expression of several menin-KMT2A target genes, including MEIS1 and FLT3. JNJ-75276617 displayed potent antiproliferative activity across several AML and acute lymphoblastic leukemia (ALL) cell lines and patient samples harboring KMT2A or NPM1 alterations in vitro. In xenograft models of AML and ALL, JNJ-75276617 reduced leukemic burden and provided a significant dose-dependent survival benefit accompanied by expression changes of menin-KMT2A target genes. JNJ-75276617 demonstrated synergistic effects with gilteritinib in vitro in AML cells harboring KMT2A-r. JNJ-75276617 further exhibited synergistic effects with venetoclax and azacitidine in AML cells bearing KMT2A-r in vitro, and significantly increased survival in mice. Interestingly, JNJ-75276617 showed potent antiproliferative activity in cell lines engineered with recently discovered mutations (MEN1M327I or MEN1T349M) that developed in patients refractory to the menin-KMT2A inhibitor revumenib. A cocrystal structure of menin in complex with JNJ-75276617 indicates a unique binding mode distinct from other menin-KMT2A inhibitors, including revumenib. JNJ-75276617 is being clinically investigated for acute leukemias harboring KMT2A or NPM1 alterations, as a monotherapy for relapsed/refractory acute leukemia (NCT04811560), or in combination with AML-directed therapies (NCT05453903).
Distribution and extent of suitable habitats of Ruspoli’s Turaco (Tauraco ruspolii) and White-cheeked Turaco (Tauraco leucotis) under a changing climate in Ethiopia
Authors: Aligaz Mulatu Ayenew , Kufa Chala Adugna , Ahmed Ahmed Seid , Argaw Hailu Tilahun , Tamrat Misganaw , Yihune Mesele , Atickem Anagaw , Bekele Afework , Bogale Bezawork Afework
Published: June 2024

Background

Understanding the distribution pattern of species and their suitable habitat is key to focus conservation efforts. Climate change has had notable impact on the distribution and extent of suitable habitats, and the long-term survival of various species. We aim to determine the distribution and extent of suitable habitats for Tauraco ruspolii and T. leucotis in Ethiopia and predict their range in the 2050s and 2070s using MaxEnt algorithm. We used 25 and 29 rarified occurrence points for T. ruspolii and T. leucotis, respectively, and 13 environmental variables. Three regularization multipliers and two cut-off thresholds were used to map the potential suitable habitats for each species under current and future climates. Maps were assembled from these techniques to produce final composite tertiary maps and investigated the habitat suitability overlap between the two species using the UNION tool in the geographical information system.

Result

All model run performances were highly accurate for both species. Precipitation of the driest month and vegetation cover are the most influential variables for the habitat suitability of T. ruspolii. The habitat suitability of T. leucotis is also mainly influenced by mean temperature of the driest quarter and vegetation cover. Under the current climate, the suitable habitat predicted for T. ruspolii covered about 24,639.19 km2, but its range size change shows a gain and increase by 156.00% and 142.68% in 2050 and 2070, respectively. The T. leucotis‘s current suitable habitat ranges about 204,397.62 km², but this is reduced by 40.84% and 68.67% in 2050 and 2070, respectively. Our modeling also showed that there was suitable habitat overlap between them at the margin of their respective habitat types in time series.

Conclusion

We concluded that there is a direct or indirect impact of climate change on the suitable habitat range expansion for T. ruspolii and contraction for T. leucotis as well as overlapping of these turaco species in different regions of Ethiopia. Therefore, understanding the distribution of current and future suitable habitats of the two turaco species can provide valuable information to implement conservation practices for the species and the regions as well.
Features of databases that supported searching for rapid evidence synthesis during COVID-19: implications for future public health emergencies
Authors: Hagerman Leah , Clark Emily C. , Neil-Sztramko Sarah E. , Colangeli Taylor , Dobbins Maureen
Published: June 2024

Background

As evidence related to the COVID-19 pandemic surged, databases, platforms, and repositories evolved with features and functions to assist users in promptly finding the most relevant evidence. In response, research synthesis teams adopted novel searching strategies to sift through the vast amount of evidence to synthesize and disseminate the most up-to-date evidence. This paper explores the key database features that facilitated systematic searching for rapid evidence synthesis during the COVID-19 pandemic to inform knowledge management infrastructure during future global health emergencies.

Methods

This paper outlines the features and functions of previously existing and newly created evidence sources routinely searched as part of the NCCMT’s Rapid Evidence Service methods, including databases, platforms, and repositories. Specific functions of each evidence source were assessed as they pertain to searching in the context of a public health emergency, including the topics of indexed citations, the level of evidence of indexed citations, and specific usability features of each evidence source.

Results

Thirteen evidence sources were assessed, of which four were newly created and nine were either pre-existing or adapted from previously existing resources. Evidence sources varied in topics indexed, level of evidence indexed, and specific searching functions.

Conclusion

This paper offers insights into which features enabled systematic searching for the completion of rapid reviews to inform decision makers within 5–10 days. These findings provide guidance for knowledge management strategies and evidence infrastructures during future public health emergencies.
Healthcare providers’ perception of caring for older patients with depression and physical multimorbidity: insights from a focus group study
Authors: Tops Laura , Cromboom Mei Lin , Tans Anouk , Deschodt Mieke , Vandenbulcke Mathieu , Vermandere Mieke
Published: June 2024

Background

The caretaking process for older adults with depression and physical multimorbidity is complex. Older patients with both psychiatric and physical illnesses require an integrated and comprehensive approach to effectively manage their care. This approach should address common risk factors, acknowledge the bidirectional relationship between somatic and mental health conditions, and integrate treatment strategies for both aspects. Furthermore, active engagement of healthcare providers in shaping new care processes is imperative for achieving sustainable change.

Objective

To explore and understand the needs and expectations of healthcare providers (HCPs) concerning the care for older patients with depression and physical multimorbidity.

Methods

Seventeen HCPs who work with the target group in primary and residential care participated in three focus group interviews. A constructivist Grounded Theory approach was applied. The results were analyzed using the QUAGOL guide.

Results

Participants highlighted the importance of patient-centeredness, interprofessional collaboration, and shared decision-making in current healthcare practices. There is also a need to further emphasize the advantages and risks of technology in delivering care. Additionally, HCPs working with this target population should possess expertise in both psychiatric and somatic care to provide comprehensive care. Care should be organized proactively, anticipating needs rather than reacting to them. Healthcare providers, including a dedicated care manager, might consider collaborating, integrating their expertise instead of operating in isolation. Lastly, effective communication among HCPs, patients, and their families is crucial to ensure high-quality care delivery.

Conclusion

The findings stress the importance of a comprehensive approach to caring for older adults dealing with depression and physical comorbidity. These insights will fuel the development of an integrated care model that caters to the needs of this population.
Associations between sarcopenia and circulating branched-chain amino acids: a cross-sectional study over 100,000 participants
Authors: Liu HuiMin , Zhang Qiang , Hao QianMeng , Li QingSheng , Yang LingFei , Yang Xuan , Wang KaiXin , Teng JunFang , Gong Zhe , Jia YanJie
Published: June 2024

Background

Emerging evidence suggests that alterations in BCAA metabolism may contribute to the pathogenesis of sarcopenia. However, the relationship between branched-chain amino acids (BCAAs) and sarcopenia is incompletely understood, and existing literature presents conflicting results. In this study, we conducted a community-based study involving > 100,000 United Kingdom adults to comprehensively explore the association between BCAAs and sarcopenia, and assess the potential role of muscle mass in mediating the relationship between BCAAs and muscle strength.

Methods

Multivariable linear regression analysis examined the relationship between circulating BCAAs and muscle mass/strength. Logistic regression analysis assessed the impact of circulating BCAAs and quartiles of BCAAs on sarcopenia risk. Subgroup analyses explored the variations in associations across age, and gender. Mediation analysis investigated the potential mediating effect of muscle mass on the BCAA-muscle strength relationship.

Results

Among 108,017 participants (mean age: 56.40 ± 8.09 years; 46.23% men), positive associations were observed between total BCAA, isoleucine, leucine, valine, and muscle mass (beta, 0.56–2.53; p < 0.05) and between total BCAA, leucine, valine, and muscle strength (beta, 0.91–3.44; p < 0.05). Logistic regression analysis revealed that increased circulating valine was associated with a 47% reduced sarcopenia risk (odds ratio = 0.53; 95% confidence interval = 0.3–0.94; p = 0.029). Subgroup analyses demonstrated strong associations between circulating BCAAs and muscle mass/strength in men and individuals aged ≥ 60 years. Mediation analysis suggested that muscle mass completely mediated the relationship between total BCAA, and valine levels and muscle strength, partially mediated the relationship between leucine levels and muscle strength, obscuring the true effect of isoleucine on muscle strength.

Conclusion

This study suggested the potential benefits of BCAAs in preserving muscle mass/strength and highlighted muscle mass might be mediator of BCAA-muscle strength association. Our findings contribute new evidence for the clinical prevention and treatment of sarcopenia and related conditions involving muscle mass/strength loss.
Childhood adversities and memory function in later life: the mediating role of activity participation
Authors: Cai Xinxin , Bai Xue , Zhou Shuai
Published: June 2024

Background

Childhood adversities may lead to decreased activity participation in later life, impacting memory health in ageing adults. Childhood adversities related to deprivation and threat, as conceptualized by the Dimensional Model of Adversity, can exhibit distinct impacts on cognitive and emotional outcomes in children and younger adults. This study examined the potential influence of childhood deprivation and threat on memory function in later life and the mediating role of activity participation in these relationships.

Methods

This study used data from the first wave of Panel Study of Active Ageing and Society (PAAS), a representative survey of Hong Kong residents aged 50 or above (N = 1,005). Key variables included late-life memory function measured by delayed recall test, deprivation- and threat-related childhood adversities, and the frequency of participation in informal and formal types of activities. Mediation tests were used for analysis.

Results

Childhood deprivation was associated with a lower late-life memory function, whereas threat was not. The negative effects of childhood deprivation and its subdomain, economic hardship, on memory function were mediated by activity participation. Total participation scores presented the strongest mediating effect (17.3–20.6%), with formal activities playing a more substantial mediating role than informal activities in mitigating the effect of childhood deprivation.

Conclusions

These findings expand the applicability of the Dimensional Model of Adversity to ageing populations, highlighting the influence of deprivation on life-long cognitive development. Furthermore, this study revealed an indirect mechanism by which childhood deprivation affects memory health in old age through diverse activity participation.
Preliminary research on LncRNA ATP2B2-IT2 in neovascularization of diabetic retinopathy
Authors: Yuan Yuan , Zhu Anming , Zeng Lan , Wang Xiaocong , Zhang Ying , Long Xiaofeng , Wu Jie , Ye Meng , He Junhao , Tan Wei
Published: June 2024

Objective

Diabetic retinopathy (DR) is a common complication of diabetes, and recent findings have shown that long noncoding RNAs (lncRNAs) may be involved in its pathogenesis. Through bioinformatics analysis, we found that lncRNA ATP2B2-IT2 may be involved in this process. This study primarily investigated the expression of the lncRNA ATP2B2-IT2 in human retinal microvascular endothelial cells (HRMECs) under high-glucose conditions and its effects on HRMEC proliferation, migration, and neovascularization.

Methods

We used RT‒PCR to assess the expression levels of lncRNA ATP2B2-IT2 and vascular endothelial growth factor (VEGF) in HRMECs under normal glucose (5.5 mmol/L) and high glucose (30 mmol/L) conditions. HRMECs were subsequently divided into four groups: the normal glucose (NG), high glucose (HG), high glucose with lncRNA ATP2B2-IT2 silencing (HG + si-lncRNA ATP2B2-IT2), and high glucose with silencing control (HG + si-NC) groups. The expression levels of the lncRNA ATP2B2-IT2 and VEGF in each group were determined using RT‒PCR. Thereafter, cell proliferation, migration, and neovascularization were assessed using CCK-8, Transwell, and tube formation assays, respectively.

Results

RT‒PCR revealed that the expression levels of the lncRNA ATP2B2-IT2 and VEGF were greater in the HG group than in the NG group (P < 0.05). After silencing of the lncRNA ATP2B2-IT2, the expression of VEGF decreased significantly (P < 0.05). Subsequent CCK-8, Transwell, and tube formation assays demonstrated that compared to those in the NG group, the HRMECs in the HG group exhibited significantly increased proliferation, migration, and neovascularization (P < 0.05). However, after silencing of the lncRNA ATP2B2-IT2, the proliferation, migration, and neovascularization of HRMECs were significantly decreased in the HG + si-lncRNA ATP2B2-IT2 group compared to those in the HG group (P < 0.05).

Conclusion

LncRNA ATP2B2-IT2 may promote the proliferation, migration and neovascularization of HRMECs under high-glucose conditions.
Characteristics of peripheral refractive errors in eyes of patients with non-amblyopic myopic anisometropia
Authors: Tong Gengmin , Jin Yuanhui , Wu Hongyan , Zhou Yao
Published: June 2024

Background

This study aims to investigate relative peripheral refractive (RPR) characteristics in children with non-amblyopic myopic anisometropia and explore potential associations between relative peripheral refractive errors (RPRE) and myopia.

Methods

Relative peripheral refractive errors were assessed in 64 children diagnosed with non-amblyopic myopic anisometropia utilizing multispectral refraction topography (MRT). Two eyes of each patient were divided into into the more myopia eyes group (ME) and the fellow eyes group (FE). Evaluated parameters encompassed total defocus values (TRDV), defocus values at eccentricities spanning 0 to 15 degrees (RDV-15), 0 to 30 degrees (RDV-30), 0 to 45 degrees (RDV-45), as well as superior (RDV-S), inferior (RDV-I), temporal (RDV-T), and nasal (RDV-N) positions.

Results

The study revealed a noteworthy contrast in TRDV values between Group ME (0.52 ± 0.36) and Group FE (0.17 ± 0.41), with a substantial significance (P < 0.0001). While no significant RDV-15 difference emerged between Group ME (0.01 ± 0.05) and Group FE (-0.01 ± 0.07) (P > 0.05), a meaningful RDV-30 difference existed between Group ME (0.11 ± 0.14) and Group FE (0.03 ± 0.19) (P = 0.0017). A significant discrepancy in RDV-45 was also observed between Group ME (0.39 ± 0.29) and Group FE (0.13 ± 0.34) (P < 0.001). Notably, RDV-I and RDV-T positions demonstrated marked differences between Group ME and Group FE (P < 0.0001), whereas no significant disparity was noted in RDV-S and RDV-N positions (P > 0.05).

Conclusion

Eyes exhibiting greater myopia manifested more hyperopic peripheral defocus in the context of anisometropia. MRT as a novel ophthalmic evaluation technique, holds promising potential for broader clinical applications in the future.
Cardiovascular disease risk and associated physical activity factors in gastrointestinal cancer survivors
Authors: Kim Su Young , Kang Hye Jung , Kim Ki-Hyun , Kim Dong Uk , Nam Seung-Joo , Yang Jae Kook , Jang Dong Kee , Choi Hyuk Soon , Ryu Dae Gon , Lee Jung Wook , Lee Jong Yoon , Park Sohee , Lee Hyun Jung
Published: June 2024

Introduction

Although the risk of CVD is increased in cancer survivors, few studies have investigated the CVD risk in survivors of gastrointestinal (GI) cancer. Therefore, we evaluated the CVD risk using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score for GI cancer survivors and associated physical activity factors.

Methods

Using the 2014–2019 Korean National Health and Nutrition Examination Surveys, data were collected for 262 GI cancer survivors and 1,310 cancer-free controls matched at a 1:5 ratio based on age and sex. The International Physical Activity Questionnaire Short-Form was used to assess physical activity, and the Euro QoL Questionnaire 5-Dimensional Classification (EQ-5D) was used to assess the health-related quality of life.

Results

A multiple logistic regression analysis demonstrated a lower risk of ASCVD in GI cancer survivors than in controls (adjusted odds ratio [aOR] = 0.73, 95% confidence interval [CI] = 0.55-0.97). Moreover, the risk of having a high ASCVD score was significantly lower in individuals who performed sufficient aerobic physical activity (aOR = 0.59, 95% CI = 0.47-0.75) and those with an EQ-5D score 1 or 2 (aOR = 0.36, 95% CI = 0.20-0.65 and aOR = 0.31, 95% CI = 0.16-0.58, respectively).

Conclusions

This population-based study demonstrated that engaging in sufficient physical activity can reduce the ASCVD risk among GI cancer survivors.