bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Imidazo[1,2‐a]pyridine‐Isoquinoline Derivatives as Potent EGFR Inhibiting Anticancer Agents
Authors: Gunuguntla Mahendar Reddy , Hanumantharayappa Manjunatha , Kumar Koppula Shiva
Published: February 2024

Herein, we synthesized some new imidazo[1,2‐a]pyridine‐isoquinoline hybrids (8 a–8 x) and investigated their anticancer activity on two human breast cancer cell lines, namely MCF‐7 and MDA‐MB231. Generally, most of them displayed higher activity on both breast cell lines than the reference drug. Specifically, compounds (2,6‐difluorophenyl)(6‐methoxy‐1‐(2‐phenylimidazo[1,2‐a]pyridin‐3‐yl)‐3,4‐dihydroisoquinolin‐2(1H)‐yl)methanone, (6‐methoxy‐1‐(2‐phenyl imidazo[1,2‐a]pyridin‐3‐yl)‐3,4‐dihydroisoquinolin‐2(1H)‐yl)(6‐methoxy pyridin‐3‐yl)methanone, (6‐methoxy‐1‐(2‐phenylimidazo[1,2‐a]pyridin‐3‐yl)‐3,4‐dihydroisoquinolin‐2(1H)‐yl)(pyrimidin‐5‐yl) methanone, 6‐methoxy‐1‐(2‐phenylimidazo[1,2‐a]pyridin‐3‐yl)‐2‐(phenylsulfonyl)‐1,2,3,4‐tetrahydro isoquinoline, 6‐methoxy‐1‐(2‐phenyl imidazo[1,2‐a]pyridin‐3‐yl)‐2‐tosyl‐1,2,3,4‐tetrahydroisoquinoline, and 6‐methoxy‐2‐((4‐methoxyphenyl)sulfonyl)‐1‐(2‐phenylimidazo[1,2‐a] pyridin‐3‐yl)‐1,2,3,4‐tetrahydroisoquinoline showed higher activity against tested cancer cell lines as compared to the erlotinib. The ability of potent compounds to inhibit the tyrosine kinase EGFR was then studied and found that compounds (6‐methoxy‐1‐(2‐phenylimidazo[1,2‐a]pyridin‐3‐yl)‐3,4‐dihydroisoquinolin‐2(1H)‐yl)(pyrimidin‐5‐yl) methanone, 6‐methoxy‐1‐(2‐phenylimidazo[1,2‐a]pyridin‐3‐yl)‐2‐tosyl‐1,2,3,4‐tetra hydroisoquinoline, and 6‐methoxy‐2‐((4‐methoxyphenyl) sulfonyl)‐1‐(2‐phenylimidazo[1,2‐a]pyridin‐3‐yl)‐1,2,3,4‐tetrahydro isoquinoline exhibited promising potency in comparison to the erlotinib. In silico investigations of the most effective compounds were also performed to find interactions with the EGFR receptor that robustly bind to the protein, and energy estimates were in good agreement with the corresponding IC50 values.
Introjected regulation and academic burnout: A moderated mediation model of social comparison and distress overtolerance
Authors: Lee Minyoung
Published: February 2024

The primary purpose of this study is to examine the mediation effect of Contrastive Upward Comparison (CUC) on the relationship between introjected regulation and exhaustion (i.e., introjected regulation—CUC—exhaustion). It is also aimed to examine the moderation effect of distress overtolerance on this mediated relationship. In order to resolve the uncertainty about the causality of cross‐sectional studies, this study worked on the relationship among the variables by setting an alternative model (i.e., CUC—introjected regulation ‐ exhaustion). The participants were 167 (females, 70.7%) undergraduate and graduate students in South Korea. The results of this study indicated that introjected regulation showed indirect and significant effect on exhaustion via CUC. However, in the alternative model, the indirect effect of introjected regulation in the relationship between CUC and exhaustion was not significant. Furthermore, high distress overtolerance buffered the relationship between introjected regulation and CUC, while it strengthened the association of CUC and exhaustion. Lastly, the results of moderated mediation suggested that students with higher distress overtolerance, experienced more CUC, and emotional exhaustion. The implications and limitations were also discussed.
AIBI Modified Mesoporous Copper Sulfide Nanocomposites for Efficient Non‐Oxygen Dependent Free Radicals‐Assisted Photothermal Therapy in Uveal Melanoma
Authors: Huang Pingping , Kong Lingdan , Zhang Feiyu , Chen Linxin , Zhang Yue , Shi Xiaoqian , Lawson Tom , Chou Shulei , Liu Yong , Wu Wencan
Published: February 2024

Uveal melanoma (UM) is an ocular cancer predominantly affecting adults, characterized by challenging diagnostic outcomes. This research endeavors to develop an innovative multifunctional nanocomposite system sensitive to near‐infrared (NIR) radiation, serving as both a non‐oxygen free‐radical generator and a photothermal agent. The designed system combines azobis isobutyl imidazoline hydrochloride (AIBI) with mesoporous copper sulfide (MCuS) nanoparticles. MCuS harnesses NIR laser energy to induce photothermal therapy, converting light energy into heat to destroy cancer cells. Simultaneously, AIBI is activated by the NIR laser to produce alkyl radicals, which induce DNA damage in remaining cancer cells. This distinctive feature equips the designed system to selectively eliminate cancers in the hypoxic tumor microenvironment. MCuS is also beneficial to scavenge the overexpressed glutathione (GSH) in the tumor microenvironment. GSH generally consumes free radicals and hiders the PDT effect. To enhance control over AIBI release in cancer cells, 1‐tetradecyl alcohol (TD), a phase‐changing material, is introduced onto the surface of MCuS nanoparticles to create the final AMPT nanoparticle system. In vitro and in vivo experiments confirm the remarkable anti‐tumor efficacy of AMPT. Notably, the study introduces an orthotopic tumor model for UM, demonstrating the feasibility of precise and effective targeted treatment within the ocular system.
Experimental study on flexural performance of composite slabs with bent bars and postcast ultrahigh‐performance concrete joints
Authors: Zhao Yong , Hong Haoyang , Liu Xian
Published: February 2024

This paper describes the use of joints with bent bars and postcast ultrahigh‐performance concrete (UHPC) joints to enable formwork‐free and support‐free construction of composite slabs. To investigate their flexural performance, static loading tests on three full‐scale simply‐supported slabs and one monolithic slab were carried out. Flexural capacity, stiffness, and crack development were recorded, resulting on flexural failure experienced by all specimens. Main cracks of composite specimens developed along the UHPC–normal concrete interface, and cracks on both sides of the UHPC joint developed evenly, similar with that of the monolithic specimen. Besides, composite slabs and a monolithic slab showed similar flexural capacity. UHPC joint was not cracked when failure occurred, and bottom bars were anchored and connected in the UHPC joint, proving that the flexural anchorage method is feasible. The average strain of the composite specimen across the UHPC joint was still consistent with the assumption of plain section, and there was an approximate linear relationship between the expansion width of the joint at the bottom of the slab and the maximum crack width at bottom bars. Moreover, middle bars contributed to the flexural capacity and stiffness of composite specimens, while horse stool reinforcement may effectively prevent the interface shear failure on the composite interface. Based on test results, the formula to control cracking of UHPC is given in this paper. The design methods on flexural capacity, stiffness, and expansion width of composite slabs are also presented and discussed.
Three‐Phase Unbalance Reduction and Energy Optimization for Active Distribution Network Using Flexible Multi‐State Switch
Authors: Jin Yixuan , Yu Moduo , Tai Nengling , Duan Ruochen , Lu Chao
Published: February 2024

Active distribution network is integrated with a large number of renewable energy sources and flexible loads such as electric vehicles(EVs). The unstable output of distributed generation and the random access to different phases cause three phase unbalance in the distribution network, which increase the energy loss and carbon emissions. Three phase unbalance reduction requires high real‐time dispatch and optimization of the power flow. This paper attempts to reduce the energy loss and carbon emission by using flexible multi‐state switch (FMSS) with optimal energy dispatch strategy. A multi‐objective optimization model is established based on second‐order cone relaxation to reduce the three‐phase unbalance and energy loss. EVs regulation strategy is proposed by analyzing their charging flexibility. A fast solution method is brought up based on second‐order cone model transformation. The effectiveness and rapidity of the method is verified by multiple cases. © 2024 Institute of Electrical Engineer of Japan and Wiley Periodicals LLC.
Performance of QUiPP App v.2 tool for prediction of preterm birth in asymptomatic high‐risk women attending preterm specialist clinic: external validation study
Authors: Creswell L. , Rolnik D. L. , Burke B. , Daly S. , O'Gorman N.
Published: February 2024

Objective

To validate externally the QUiPP App v.2 algorithms in an independent cohort of high‐risk asymptomatic women attending a preterm birth (PTB) surveillance clinic in Ireland.

Methods

This was a retrospective, single‐center, observational study assessing discrimination and calibration of the QUiPP App v.2 at six predetermined clinical timepoints (PTB at < 30, < 34 and < 37 weeks of pregnancy and PTB within 1, 2 and 4 weeks of testing). Discrimination was assessed by estimating the area under the receiver‐operating‐characteristics curve (AUC) and sensitivity at fixed false‐positive rates of 5%, 10% and 20%. Model calibration was assessed to evaluate the concordance between expected and observed outcomes. P‐values < 0.05 were considered statistically significant. No adjustments for treatment effects were made.

Results

Overall, 762 women with 1660 PTB surveillance clinic visits using the QUiPP App v.2 between 2019 and 2022 were analyzed. The study population included 142 (18.6%) patients who later experienced PTB. The QuiPP App's performance in the prediction of short‐term outcomes, such as birth within 1 week (AUC, 0.866 (95% CI, 0.755–0.955)), 2 weeks (AUC, 0.721 (95% CI, 0.569–0.854)) and 4 weeks (AUC, 0.775 (95% CI, 0.699–0.842)), and delivery at < 30 weeks (AUC, 0.747 (95% CI, 0.613–0.865)), was superior to its ability to predict longer‐term outcomes (PTB at < 37 weeks: AUC, 0.631 (95% CI, 0.596–0.668)). Calibration was generally good for low‐risk results, as the predicted risk in these patients tended to match the observed incidence. However, in women deemed to be at greater risk of PTB, the predicted probability superseded the observed incidence of PTB.

Conclusions

The QUiPP App v.2 accurately discriminates women who are at short‐term risk of PTB. A ‘treatment paradox’ may influence calibration in high‐risk women. Further research is needed to ascertain if QuiPP treatment thresholds can be safely adjusted in women receiving prophylactic treatment to prevent PTB, and whether this improves the outcome. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Stage‐based recipient and donor outcome in twin‐to‐twin transfusion syndrome treated by fetoscopic laser surgery using Solomon technique
Authors: Kyvernitakis I. , Rosner M. , Birk A. , Goodman L. , Herlands L. , Wohlmuth P. , Laurie M. , Millard S. , Kush M. , Miller J. , Baschat A. A.
Published: February 2024

Objective

To evaluate twin survival stratified by Quintero stage in patients with twin‐to‐twin transfusion syndrome (TTTS) after Solomon laser treatment.

Methods

This was a single‐center study at Johns Hopkins Center for Fetal Therapy, investigating a cohort of consecutive twin pregnancies treated with the Solomon laser technique for TTTS. Preoperative Quintero stage, perioperative characteristics and obstetric factors were investigated in relation to neonatal survival of the recipient and donor twins at discharge. Determinants of twin survival were evaluated using univariate logistic regression and cumulative survival probability analyses.

Results

Of 402 pregnancies with TTTS that underwent Solomon laser treatment, 80 (19.9%) were diagnosed with Quintero Stage‐I TTTS, 126 (31.3%) with Stage II, 169 (42.0%) with Stage III and 27 (6.7%) with Stage IV. Post‐laser twin anemia polycythemia sequence or recurrent TTTS occurred in 19 (4.7%) patients and 11 (2.7%) required repeat laser surgery. Preterm prelabor rupture of membranes occurred in 150 (37.3%) patients and median gestational age at delivery was 32 + 1 weeks. In 303 (75.4%) patients, both twins were alive at discharge; 67/80 (83.8%) were Stage I, 101/126 (80.2%) were Stage II, 113/169 (66.9%) were Stage III and 22/27 (81.5%) were Stage IV (P = 0.062). Donor twin survival was lower than that of recipients in cases with Stage‐III TTTS (118/169 (69.8%) vs 145/169 (85.8%) (χ2 = 26.076, P < 0.0001)). Higher intertwin size discordance and absent or reversed umbilical artery (UA) end‐diastolic velocity (EDV) were associated with donor demise (Nagelkerke R2, 0.38; P < 0.001). Overall, spontaneous post‐laser donor demise occurred in 53 (39.6%) patients, accounting for the majority of all losses. Cumulative donor survival decreased from 92% to 65% when intertwin size discordance was >30% and to 48% when UA‐EDV was absent or reversed (P < 0.001).

Conclusions

The Solomon laser technique achieves TTTS resolution and double twin survival in a high proportion of cases. Recipient and donor survival is comparable unless there is significant intertwin size discordance and placental dysfunction. This degree of unequal placental sharing, typically found in Stage‐III TTTS, is the primary factor preventing double survival due to a higher rate of donor demise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
‘All I do is fight fires’: Qualitative exploration of UK veterinarians’ attitudes towards and experiences of pre‐purchase consultations regarding brachycephalic dogs
Authors: Pound Lauren , Farrow Michelle , O'Neill Dan , Deane David J. , Packer Rowena M. A.
Published: February 2024

Background

Demand for brachycephalic dogs has dramatically increased over the past decade, despite growing evidence of strong associations between brachycephaly and severe, chronic disease. Positive post‐purchase attitudes of owners towards brachycephalic dogs are highly intractable, facilitated by normalisation of breed‐related disease and strong dog–owner bonds. Veterinarian‐led pre‐purchase consultations (PPCs) have been promoted as an opportunity to influence acquisition decisions regarding brachycephalic dogs.

Methods

Using reflexive thematic analysis, this qualitative study investigated veterinarians’ attitudes towards, and experiences of, engaging in PPCs for brachycephalic dogs.

Results

Veterinarians described significant structural barriers, such as lack of time and staff, and perceptual barriers, such as perceived futility, negative outcomes of PPCs and public distrust in the profession, that combine to inhibit many veterinarians from offering or delivering brachycephalic PPCs. Some of these barriers are intractable at an individual‐veterinarian level and lead to moral distress due to conflicts between veterinarians’ responsibilities to animal welfare versus clients' and business needs, with resultant censorship of authentic views on brachycephalic ownership compromising professional integrity and autonomy.

Limitations

Wider views and/or experiences may exist outside of the sampled population.

Conclusion

Stronger veterinary leadership, including from the RCVS, BVA and veterinary corporates, is now urgently required to build profession‐wide solutions that overcome the barriers identified to create public‐facing consensus and innovative solutions to the ‘brachycephalic crisis’.
Preventable deaths in hospitalized trauma patients
Authors: Alao David O. , Cevik Arif Alper , Al Shamsi Fayez , Mousa Hussam , Elnikety Sherif , Benour Mahmoud , Al‐Bluwi Ghada S. M. , Abu‐Zidan Fikri M.
Published: February 2024

Aim

To study the preventable trauma deaths of hospitalized patients in the United Arab Emirates and to identify opportunities for improvement.

Methods

We analyzed the Abu Dhabi Emirate Trauma Registry data of admitted patients who died in the emergency department or in hospital from 2014 to 2019. A panel of experts categorize the deaths into not preventable (NP), potentially preventable (PP), and definitely preventable (DP).

Results

A total of 405 deaths were included, and 82.7% were males. The majority (89.1%) were NP, occurring mainly in the emergency department (40.4%) and the intensive care unit (49.9%). The combined potentially preventable and preventable death rate was 10.9%. The median (Interquartile range) age of the DP was 57.5 (37–76) years, compared with 32 (24–42) and 34 (25–55) years for NP and PP, respectively (p = 0.008). Most of the PP deaths occurred in the intensive care unit (55.6%), while the DP occurred mainly in the ward (50%). Falls accounted for 25% of PP and DP. Deficiencies in airway care, hemorrhage control, and fluid management were identified in 25%, 43.2% and 29.5% of the DP/PP deaths, respectively. Seventy‐two percent of the Airway deficiencies occurred in the prehospital, while 34.1% of hemorrhage control deficiencies were in the emergency department. Fluid management deficiencies occurred in the emergency department and the operation theater.

Conclusions

DP and PP deaths comprised 10.9% of the deaths. Most of the DP occurred in the emergency department and ward. Prehospital Airway and in‐hospital hemorrhage and excessive fluid were the main areas for opportunities for improvement.
Mobile Devices and Autonomy: Individual-Level Effects
Authors: Aylsworth Timothy , Castro Clinton
Published: February 2024

In this chapter, we offer a review of the empirical findings that animate our concerns about the effects of mobile devices on individuals (the troublesome findings about the effects of mobile devices on collectives is reviewed in Chap. 7). We begin by clarifying what we mean by mobile devices, noting that these devices are not our only concern. We also explain why they are our primary concern. In short, we are especially concerned by mobile devices because their mobility, combined with their ability to track our behavior and provide real-time feedback to it, make them powerful behavior modification devices. After explaining how mobile devices can modify our behavior and why—given the structure of the attention economy—the interests of the developers of these technologies are not always in alignment with our own, we show that there is reason to think that mobile devices have detrimental effects on all eight facets of autonomy outlined in the preceding chapter.
The Duty to Promote Digital Minimalism in Ourselves
Authors: Aylsworth Timothy , Castro Clinton
Published: February 2024

In the 1950s, duties to the self became unpopular in mainstream moral philosophy. We explain why some ethicists became skeptical of them, and we present Kant’s position on duties to oneself. Kantian moral philosophers have long maintained the existence of duties to oneself. After presenting this historical backdrop, we then provide our definition of digital minimalism; we understand this as a virtue—a robust disposition to do what is morally required. Given the conclusions of the last two chapters (viz. that autonomy matters morally and that mobile devices undermine autonomy), we argue that you have a moral duty to protect your autonomy from this threat. We define digital minimalism as the disposition to use mobile devices for a reasonable amount of time in light of your chosen ends. We conclude by showing how this duty fits in within the broader taxonomy of Kant’s ethical duties. In our view, the duty to be a digital minimalist is an imperfect duty because it is a duty to promote an obligatory end (one’s own perfection).
China-ASEAN Cooperation Under the BRI
Authors: Yu Hong
Published: February 2024

Southeast Asia has historically been a loose, pluralistic and non-uniform region that has never had a single name or a single geographical identity. Different people of the region have different perceptions and different interpretations.
The China-Singapore Chongqing Connectivity Project: A Cornerstone for Bilateral Relations
Authors: Yu Hong
Published: February 2024

As part of a country’s overall diplomatic strategy, (Hocking, Localizing Foreign Policy: Non-Central Governments and Multilayered Diplomacy, Palgrave Macmillan, London, 1993) argues that its central government can effectively use local external cooperation to break down sensitive and difficult political issues to the local level, thereby helping to reduce external pressures on the central government and helping state institutions to reduce the burden of complex policy implementations.
Coalescence of Geodesics and the BKS Midpoint Problem in Planar First-Passage Percolation
Authors: Dembin Barbara , Elboim Dor , Peled Ron
Published: February 2024

We consider first-passage percolation on $\mathbb{Z}^{2}$ with independent and identically distributed weights whose common distribution is absolutely continuous with a finite exponential moment. Under the assumption that the limit shape has more than 32 extreme points, we prove that geodesics with nearby starting and ending points have significant overlap, coalescing on all but small portions near their endpoints. The statement is quantified, with power-law dependence of the involved quantities on the length of the geodesics.

The result leads to a quantitative resolution of the Benjamini–Kalai–Schramm midpoint problem. It is shown that the probability that the geodesic between two given points passes through a given edge is smaller than a power of the distance between the points and the edge.

We further prove that the limit shape assumption is satisfied for a specific family of distributions.

Lastly, related to the 1965 Hammersley–Welsh highways and byways problem, we prove that the expected fraction of the square {−n,…,n}2 which is covered by infinite geodesics starting at the origin is at most an inverse power of n. This result is obtained without explicit limit shape assumptions.
User-centered AI-based voice-assistants for safe mobility of older people in urban context
Authors: Jnr. Bokolo Anthony
Published: February 2024

Voice-assistants are becoming increasingly popular and can be deployed to offers a low-cost tool that can support and potentially reduce falls, injuries, and accidents faced by older people within the age of 65 and older. But, irrespective of the mobility and walkability challenges faced by the aging population, studies that employed Artificial Intelligence (AI)-based voice-assistants to reduce risks faced by older people when they use public transportation and walk in built environment are scarce. This is because the development of AI-based voice-assistants suitable for the mobility domain presents several techno–social challenges. Accordingly, this study aims to identify user-centered service design and functional requirements, techno–social factors, and further design an architectural model for an AI-based voice-assistants that provide personalized recommendation to reduce falls, injuries, and accidents faced by older people. Accordingly, a scoping review of the literature grounded on secondary data from 59 studies was conducted and descriptive analysis of the literature and content-related analysis of the literature was carried out. Findings from this study presents the perceived techno-socio factors that may influences older people use of AI-based voice-assistants. More importantly, this study presents user-centred service design and functional requirements needed to be considered in developing voice-assistants suitable for older people. Implications from this study provides AI techniques for implementing voice-assistants that provide safe mobility, walkability, and wayfinding for older people in urban areas.
Comparison of the symmetric hyperbolic thermodynamically compatible framework with Hamiltonian mechanics of binary mixtures
Authors: Sýkora Martin , Pavelka Michal , Peshkov Ilya , Minakowski Piotr , Klika Václav , Romenski Evgeniy
Published: February 2024

How to properly describe continuum thermodynamics of binary mixtures where each constituent has its own momentum? The Symmetric Hyperbolic Thermodynamically Consistent (SHTC) framework and Hamiltonian mechanics in the form of the General Equation for Non-Equilibrium Reversible-Irreversible Coupling (GENERIC) provide two answers, which are similar but not identical, and are compared in this article. They are compared both analytically and numerically on several levels of description, varying in the amount of detail. Namely, a reduction to a more common one-momentum setting is shown, where the effects of the second momentum translate into diffusive fluxes. Both SHTC and GENERIC can thus be interpreted as a method specifying diffusive flux in standard theory. The GENERIC equations, stemming from the Liouville equation, contain terms expressing self-advection of the relative velocity by itself, which lead to a vorticity-dependent diffusion matrix after the reduction. The SHTC equations, on the other hand, do not contain such terms. We also discuss the possibility to formulate a theory of mixtures with two momenta and only one temperature that is compatible with the Liouville equation and possesses the Hamiltonian structure, including Jacobi identity.
Hölder continuity of weak solutions to evolution equations with distributed order fractional time derivative
Authors: Kubica Adam , Ryszewska Katarzyna , Zacher Rico
Published: February 2024

We study the regularity of weak solutions to evolution equations with distributed order fractional time derivative. We prove a weak Harnack inequality for nonnegative weak supersolutions and Hölder continuity of weak solutions to this problem. Our results substantially generalise analogous known results for the problem with single order fractional time derivative.
Removing outliers from the normative database improves regional atrophy detection in single-subject voxel-based morphometry
Authors: Schultz Vivian , Hedderich Dennis M. , Schmitz-Koep Benita , Schinz David , Zimmer Claus , Yakushev Igor , Apostolova Ivayla , Özden Cansu , Opfer Roland , Buchert Ralph
Published: February 2024

Purpose

Single-subject voxel-based morphometry (VBM) compares an individual T1-weighted MRI to a sample of normal MRI in a normative database (NDB) to detect regional atrophy. Outliers in the NDB might result in reduced sensitivity of VBM. The primary aim of the current study was to propose a method for outlier removal (“NDB cleaning”) and to test its impact on the performance of VBM for detection of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD).

Methods

T1-weighted MRI of 81 patients with biomarker-confirmed AD (n = 51) or FTLD (n = 30) and 37 healthy subjects with simultaneous FDG-PET/MRI were included as test dataset. Two different NDBs were used: a scanner-specific NDB (37 healthy controls from the test dataset) and a non-scanner-specific NDB comprising 164 normal T1-weighted MRI from 164 different MRI scanners. Three different quality metrics based on leave-one-out testing of the scans in the NDB were implemented. A scan was removed if it was an outlier with respect to one or more quality metrics. VBM maps generated with and without NDB cleaning were assessed visually for the presence of AD or FTLD.

Results

Specificity of visual interpretation of the VBM maps for detection of AD or FTLD was 100% in all settings. Sensitivity was increased by NDB cleaning with both NDBs. The effect was statistically significant for the multiple-scanner NDB (from 0.47 [95%-CI 0.36–0.58] to 0.61 [0.49–0.71]).

Conclusion

NDB cleaning has the potential to improve the sensitivity of VBM for the detection of AD or FTLD without increasing the risk of false positive findings.
Comparison of AirSeal versus conventional insufflation system for retroperitoneal robot-assisted laparoscopic partial nephrectomy: a randomized controlled trial
Authors: Wei Mengchao , Yang Wenjie , Zhou Jingmin , Ye Zixing , Ji Zhigang , Dong Jie , Xu Weifeng
Published: February 2024

Purpose

AirSeal is a valve-less trocar insufflation system which is widely used in robotic urologic surgeries. More evidence is needed concerning the application and cost of AirSeal in retroperitoneal robot-assisted laparoscopic partial nephrectomy.

Methods

We conducted a randomized controlled trial enrolling 62 patients who underwent retroperitoneal robot-assisted laparoscopic partial nephrectomy from February 2022 to February 2023 in the Peking Union Medical College Hospital. Patients were randomly assigned into AirSeal insufflation (AIS) group and conventional insufflation (CIS) group. The primary outcome was the rate of subcutaneous emphysema (SCE).

Results

The SCE rate in the AIS group (12.9%) was significantly lower than that in the CIS group (35.5%) (P = 0.038). Lower maximum end-tidal carbon dioxide (CO2) (41 vs 45 mmHg, P = 0.011), PaCO2 at the end of the operation (40 vs 45 mmHg, P < 0.001), maximum tidal volume (512 vs 570 ml, P = 0.003), frequency of lens cleaning (3 vs 5, P < 0.001), pain score at 8 h (3 vs 4, P = 0.025), 12 h (2 vs 3, P = 0.029) postoperatively and at time of discharge (1 vs 2, P = 0.002) were observed in the AIS group, despite a higher hospitalization cost (68,197 vs 64658RMB, P < 0.001). Logistic regression analysis identified insufflation approach was the only influencing factor for the occurrence of SCE events.

Conclusion

AirSeal insufflation system exhibited similar efficacy and improved safety for retroperitoneal robot-assisted laparoscopic partial nephrectomy than conventional insufflation system, despite an affordable increase of hospitalization costs.
The effect of off-label use of reduced-dose direct oral anticoagulants therapy in the treatment of pulmonary embolism comparable to standard-dose therapy
Authors: Yamazoe Shinji , Imai Hajime , Ogawa Yasuhiro , Kano Naoaki , Murase Yosuke , Mamiya Keita , Ikeda Tomoyo , Hiramatsu Kei , Torii Jun , Kawaguchi Katsuhiro
Published: February 2024

Direct oral anticoagulants (DOACs) have been shown to be effective and safe in preventing pulmonary embolism recurrence. In this single-center retrospective observational study, we aimed to evaluate the efficacy and safety of reduced-dose DOACs in 86 consecutive patients with acute pulmonary embolism. Patients were divided into standard-dose and reduced-dose DOACs groups. Initial clot volume did not significantly differ between the two groups (standard-dose DOACs vs. reduced-dose DOACs, 18.8 [Q1–Q3 7.3–30.8] mL vs. 10.0 [Q1–Q3 3.2–27.9] mL, p = 0.1). Follow-up computed tomography (CT) within 30 days showed a higher rate of clot volume reduction or disappearance in the standard-dose group compared to the reduced-dose group (standard-dose DOACs vs. reduced-dose DOACs, 81.6% vs. 53.9%, p = 0.02). However, at the final follow-up CT, there was no significant difference in clot volume change between the two groups (standard-dose DOACs vs. reduced-dose DOACs, 91.5% vs. 82.0%, p = 0.19). Major bleeding occurred in two patients in the standard-dose group (4.3%) and three patients in the reduced-dose DOACs group (7.7%) (p = 0.5). In conclusion, while standard-dose DOACs demonstrated superior efficacy in early clot reduction, reduced doses of apixaban and edoxaban showed comparable efficacy and safety profiles in long-term treatment of acute pulmonary embolism in certain patients.
The effect of missing data on evolutionary analysis of sequence capture bycatch, with application to an agricultural pest
Authors: Featherstone Leo A. , McGaughran Angela
Published: February 2024

Sequence capture is a genomic technique that selectively enriches target sequences before high throughput next-generation sequencing, to generate specific sequences of interest. Off-target or ‘bycatch’ data are often discarded from capture experiments, but can be leveraged to address evolutionary questions under some circumstances. Here, we investigated the effects of missing data on a variety of evolutionary analyses using bycatch from an exon capture experiment on the global pest moth, Helicoverpa armigera. We added > 200 new samples from across Australia in the form of mitogenomes obtained as bycatch from targeted sequence capture, and combined these into an additional larger dataset to total > 1000 mitochondrial cytochrome c oxidase subunit I (COI) sequences across the species’ global distribution. Using discriminant analysis of principal components and Bayesian coalescent analyses, we showed that mitogenomes assembled from bycatch with up to 75% missing data were able to return evolutionary inferences consistent with higher coverage datasets and the broader literature surrounding H. armigera. For example, low-coverage sequences broadly supported the delineation of two H. armigera subspecies and also provided new insights into the potential for geographic turnover among these subspecies. However, we also identified key effects of dataset coverage and composition on our results. Thus, low-coverage bycatch data can offer valuable information for population genetic and phylodynamic analyses, but caution is required to ensure the reduced information does not introduce confounding factors, such as sampling biases, that drive inference. We encourage more researchers to consider maximizing the potential of the targeted sequence approach by examining evolutionary questions with their off-target bycatch where possible—especially in cases where no previous mitochondrial data exists—but recommend stratifying data at different genome coverage thresholds to separate sampling effects from genuine genomic signals, and to understand their implications for evolutionary research.
Safety and efficacy of new staple-line reinforcement in lung resection: a prospective study of 48 patients
Authors: Mitsui Suguru , Tanaka Yugo , Nishikubo Megumi , Doi Takefumi , Tane Shinya , Hokka Daisuke , Mitomo Yuji , Maniwa Yoshimasa
Published: February 2024

Purpose

To evaluate the safety and efficacy of new staple-line reinforcement (SLR) in pulmonary resection through a prospective study and to compare the results of this study with historical control data in an exploratory study.

Methods

The subjects of this study were 48 patients who underwent thoracoscopic lobectomy. The primary endpoint was air leakage from the staple line. The secondary endpoints were the location of air leakage, duration of air leakage, and postoperative pulmonary complications.

Results

The incidence of intraoperative air leakage from the staple line was 6.3%. Three patients had prolonged air leakage as a postoperative pulmonary complication. No malfunction was found in patients who underwent SLR with the stapling device. When compared with the historical group, the SLR group had a significantly lower incidence of air leakage from the staple line (6.3% vs. 28.5%, P < 0.001) and significantly shorter indwelling chest drainage time (P = 0.049) and length of hospital stay (P < 0.001).

Conclusions

The use of SLR in pulmonary resection was safe and effective. When compared with conventional products, SLR could control intraoperative air leakage from the staple line and shorten time needed for indwelling chest drainage and the length of hospital stay.
Formally verifying decompositions of stochastic specifications
Authors: Hampus Anton , Nyberg Mattias
Published: February 2024

According to the principles of compositional verification, verifying that lower-level components satisfy their specification ensures that the whole system satisfies its top-level specification. The key step is to ensure that the lower-level specifications constitute a correct decomposition of the top-level specification. In a non-stochastic context, such decomposition can be analyzed using techniques of theorem proving. In industrial applications, especially in safety-critical systems, specifications are often of stochastic nature, for example, giving a bound on the probability that a system failure will occur before a given time. A decomposition of such a specification requires techniques beyond traditional theorem proving. The first contribution of the paper is a theoretical framework that allows the representation of, and reasoning about, stochastic and timed behavior of systems as well as specifications for such behavior. The framework is based on traces that describe the continuous-time evolution of a system, and specifications are formulated using timed automata combined with probabilistic acceptance conditions. The second contribution is a novel approach to verifying decompositions of such specifications by reducing the problem to checking emptiness of the solution space for a system of linear inequalities.
Forecasting first-year student mobility using explainable machine learning techniques
Authors: Litmeyer Marie-Louise , Hennemann Stefan
Published: February 2024

In the context of regional sciences and migration studies, gravity and radiation models are typically used to estimate human spatial mobility of all kinds. These formal models are incorporated as part of regression models along with co-variates, to better represent regional specific aspects. Often, the correlations between dependent and independent variables are of non-linear type and follow complex spatial interactions and multicollinearity. To address some of the model-related obstacles and to arrive at better predictions, we introduce machine learning algorithm class XGBoost to the estimation of spatial interactions and provide useful statistics and visual representations for the model evaluation and the evaluation and interpretation of the independent variables. The methods suggested are used to study the case of the spatial mobility of high-school graduates to the enrolment in higher education institutions in Germany at the county-level. We show that machine learning techniques can deliver explainable results that compare to traditional regression modeling. In addition to typically high model fits, variable-based indicators such as the Shapley Additive Explanations value (SHAP) provide significant additional information on the differentiated and non-linear effect of the variable values. For instance, we provide evidence that the initial study location choice is not related to the quality of local labor-markets in general, as there are both, strong positive and strong negative effects of the local academic employment rates on the migration decision. When controlling for about 28 co-variates, the attractiveness of the study location itself is the most important single factor of influence, followed by the classical distance-related variables travel time (gravitation) and regional opportunities (radiation). We show that machine learning methods can be transparent, interpretable, and explainable, when employed with adequate domain-knowledge and flanked by additional calculations and visualizations related to the model evaluation.
Post-sepsis psychiatric disorder: Pathophysiology, prevention, and treatment
Authors: Li Dayong , Zhang Xujie , Lu Yuru , Jing Liang , Hu Hongjie , Song Yaqin , Wu Shuhui , Zhu Wei
Published: February 2024

Post-sepsis psychiatric disorder, encompassing anxiety, depression, post-traumatic stress disorder and delirium, is a highly prevalent complication secondary to sepsis, resulting in a marked increase in long-term mortality among affected patients. Regrettably, psychiatric impairment associated with sepsis is frequently disregarded by clinicians. This review aims to summarize recent advancements in the understanding of the pathophysiology, prevention, and treatment of post-sepsis mental disorder, including coronavirus disease 2019-related psychiatric impairment. The pathophysiology of post-sepsis psychiatric disorder is complex and is known to involve blood–brain barrier disruption, overactivation of the hypothalamic–pituitary–adrenal axis, neuroinflammation, oxidative stress, neurotransmitter dysfunction, programmed cell death, and impaired neuroplasticity. No unified diagnostic criteria for this disorder are currently available; however, screening scales are often applied in its assessment. Modifiable risk factors for psychiatric impairment post-sepsis include the number of experienced traumatic memories, the length of ICU stay, level of albumin, the use of vasopressors or inotropes, daily activity function after sepsis, and the cumulative dose of dobutamine. To contribute to the prevention of post-sepsis psychiatric disorder, it may be beneficial to implement targeted interventions for these modifiable risk factors. Specific therapies for this condition remain scarce. Nevertheless, non-pharmacological approaches, such as comprehensive nursing care, may provide a promising avenue for treating psychiatric disorder following sepsis. In addition, although several therapeutic drugs have shown preliminary efficacy in animal models, further confirmation of their potential is required through follow-up clinical studies.
Intraoperative haemodynamic monitoring and management of adults having non-cardiac surgery: Guidelines of the German Society of Anaesthesiology and Intensive Care Medicine in collaboration with the German Association of the Scientific Medical Societies
Authors: Saugel Bernd , Annecke Thorsten , Bein Berthold , Flick Moritz , Goepfert Matthias , Gruenewald Matthias , Habicher Marit , Jungwirth Bettina , Koch Tilo , Kouz Karim , Meidert Agnes S , Pestel Gunther , Renner Jochen , Sakka Samir G , Sander Michael , Treskatsch Sascha , Zitzmann Amelie , Reuter Daniel A
Published: February 2024

Haemodynamic monitoring and management are cornerstones of perioperative care. The goal of haemodynamic management is to maintain organ function by ensuring adequate perfusion pressure, blood flow, and oxygen delivery. We here present guidelines on “Intraoperative haemodynamic monitoring and management of adults having non-cardiac surgery” that were prepared by 18 experts on behalf of the German Society of Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für Anästhesiologie und lntensivmedizin; DGAI).
Generalisation challenges in deep learning models for medical imagery: insights from external validation of COVID-19 classifiers
Authors: Haynes Sophie Crawford , Johnston Pamela , Elyan Eyad
Published: February 2024

The generalisability of deep neural network classifiers is emerging as one of the most important challenges of our time. The recent COVID-19 pandemic led to a surge of deep learning publications that proposed novel models for the detection of COVID-19 from chest x-rays (CXRs). However, despite the many outstanding metrics reported, such models have failed to achieve widespread adoption into clinical settings. The significant risk of real-world generalisation failure has repeatedly been cited as one of the most critical concerns, and is a concern that extends into general medical image modelling. In this study, we propose a new dataset protocol and, using this, perform a thorough cross-dataset evaluation of deep neural networks when trained on a small COVID-19 dataset, comparable to those used extensively in recent literature. This allows us to quantify the degree to which these models can generalise when trained on challenging, limited medical datasets. We also introduce a novel occlusion evaluation to quantify model reliance on shortcut features. Our results indicate that models initialised with ImageNet weights then fine-tuned on small COVID-19 datasets, a standard approach in the literature, facilitate the learning of shortcut features, resulting in unreliable, poorly generalising models. In contrast, pre-training on related CXR imagery can stabilise cross-dataset performance. The CXR pre-trained models demonstrated a significantly smaller generalisation drop and reduced feature dependence outwith the lung region, as indicated by our occlusion test. This paper demonstrates the challenging problem of model generalisation, and the need for further research on developing techniques that will produce reliable, generalisable models when learning with limited datasets.
The distinctly zetetic significance of disagreement
Authors: Pharr Quentin
Published: February 2024

Recent debates about disagreement’s significance have largely focused on its epistemic significance. However, given how much attention has already been paid to its epistemic significance, we might well wonder: what significance might disagreement have when we consider other related normative domains? And, in particular, what significance might it have when we consider the broader domain of inquiry, or what some thinkers have called either the “zetetic” or “erotetic” domain? In response, this paper suggest three things. Firstly, it suggests how we might clarify the relations among the epistemic, erotetic, and zetetic domains of normativity, given their potential differences and incompatibilities. Then, it suggests that disagreement’s significance within inquiry can either be tied to erotetic norms or to either of two sorts of zetetic norms: vindication-directed or possession-directed norms. And finally, it suggests preferred answers to the question of what disagreement’s distinctly zetetic significance might be, given the participating inquirers’ ordinarily-conceived zetetic standings and how their sets of dialectically accessible evidence might compare.
DIF Analysis with Unknown Groups and Anchor Items
Authors: Wallin Gabriel , Chen Yunxiao , Moustaki Irini
Published: February 2024

Ensuring fairness in instruments like survey questionnaires or educational tests is crucial. One way to address this is by a Differential Item Functioning (DIF) analysis, which examines if different subgroups respond differently to a particular item, controlling for their overall latent construct level. DIF analysis is typically conducted to assess measurement invariance at the item level. Traditional DIF analysis methods require knowing the comparison groups (reference and focal groups) and anchor items (a subset of DIF-free items). Such prior knowledge may not always be available, and psychometric methods have been proposed for DIF analysis when one piece of information is unknown. More specifically, when the comparison groups are unknown while anchor items are known, latent DIF analysis methods have been proposed that estimate the unknown groups by latent classes. When anchor items are unknown while comparison groups are known, methods have also been proposed, typically under a sparsity assumption – the number of DIF items is not too large. However, DIF analysis when both pieces of information are unknown has not received much attention. This paper proposes a general statistical framework under this setting. In the proposed framework, we model the unknown groups by latent classes and introduce item-specific DIF parameters to capture the DIF effects. Assuming the number of DIF items is relatively small, an <mml:math xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mnf="http://cambridge.org/core/manifest" xmlns:cup="http://contentservices.cambridge.org" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:m="http://cambridge.org/core/metadata" xmlns:core="http://cambridge.org/core" xmlns:c="http://cambridge.org/core/content">L1\documentclass[12pt]{minimal}
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\begin{document}$$L_1$$\end{document}-regularised estimator is proposed to simultaneously identify the latent classes and the DIF items. A computationally efficient Expectation-Maximisation (EM) algorithm is developed to solve the non-smooth optimisation problem for the regularised estimator. The performance of the proposed method is evaluated by simulation studies and an application to item response data from a real-world educational test.