bluuebunny/crossref_metadata_2025 huggingface dataset:
Frailty model with change points for survival analysis
Authors: Kojima Masahiro , Orihara Shunichiro
Published: January 2024

We propose a novel frailty model with change points applying random effects to a Cox proportional hazard model to adjust the heterogeneity between clusters. In the specially focused eight Empowered Action Group (EAG) states in India, there are problems with different survival curves for children up to the age of five in different states. Therefore, when analyzing the survival times for the eight EAG states, we need to adjust for the effects among states (clusters). Because the frailty model includes random effects, the parameters are estimated using the expectation‐maximization (EM) algorithm. Additionally, our model needs to estimate change points; we thus propose a new algorithm extending the conventional estimation algorithm to the frailty model with change points to solve the problem. We show a practical example to demonstrate how to estimate the change point and the parameters of the distribution of random effect. Our proposed model can be easily analyzed using the existing R package. We conducted simulation studies with three scenarios to confirm the performance of our proposed model. We re‐analyzed the survival time data of the eight EAG states in India to show the difference in analysis results with and without random effect. In conclusion, we confirmed that the frailty model with change points has a higher accuracy than the model without a random effect. Our proposed model is useful when heterogeneity needs to be taken into account. Additionally, the absence of heterogeneity did not affect the estimation of the regression parameters.
PTOV1‐AS1 desensitizes colorectal cancer cells to 5‐FU through depressing miR‐149‐5p to activate the positive feedback loop with Wnt/β‐catenin pathway
Authors: Chen Yanan , Mao Xiaobei , Xu Yichen , Li Lin , Geng Jian , Dai Tingting , Wang Qian , Xue Lijun , Tao Leilei , Liu Xiaobei
Published: January 2024

5‐Fluorouracil is a commonly used chemotherapy drug for colorectal cancer. Resistance to 5‐Fluorouracil remains a challenge. This research aimed to explore the mechanism of 5‐Fluorouracil resistance in colorectal cancer. RT‐qPCR and Western blot were used to determine the RNA and protein expression in both cells and exosome. Assays in vitro and in vivo were performed to measure the role of miR‐149‐5p in colorectal cancer cells. RIP, luciferase activity report, and RNA pulldown assay were applied to detect the association of PTOV1‐AS1, SUV39H1, miR‐149‐5p, and FOXM1. MiR‐149‐5p was down‐expressed in 5‐Fluorouracil‐resistant cells. MiR‐149‐5p enhanced the effectiveness of 5‐Fluorouracil both in vitro and in vivo. Sensitive colorectal cancer cells released exosomal miR‐149‐5p to sensitize resistant cells to chemotherapy. Mechanistically, miR‐149‐5p targeted the FOXM1 to inactivate Wnt/β‐catenin pathway, and PTOV1‐AS1 recruited SUV39H1 to suppress miR‐149‐5p transcription, in turn activating Wnt/β‐catenin pathway, and forming a positive feedback loop with FOXM1. PTOV1‐AS1 inhibits miR‐149‐5p by a positive feedback loop with FOXM1‐mediated Wnt/β‐catenin pathway, which provides insights into a potential novel target for enhancing the effectiveness of chemotherapy in colorectal cancer patients.
Chirped Pulses Meet Quantum Dots: Innovations, Challenges, and Future Perspectives
Authors: Kappe Florian , Karli Yusuf , Wilbur Grant , Krämer Ria G. , Ghosh Sayan , Schwarz René , Kaiser Moritz , Bracht Thomas K. , Reiter Doris E. , Nolte Stefan , Hall Kimberley C. , Weihs Gregor , Remesh Vikas
Published: January 2024

Shaped laser pulses have been remarkably effective in investigating various aspects of light–matter interactions spanning a broad range of research. Chirped laser pulses exhibiting a time‐varying frequency, or quadratic spectral phase, form a crucial category in the group of shaped laser pulses. This type of pulses have made a ubiquitous presence from spectroscopic applications to developments in high‐power laser technology, and from nanophotonics to quantum optical communication, ever since their introduction. In the case of quantum technologies recently, substantial efforts are being invested toward achieving a truly scalable architecture. Concurrently, it is important to develop methods to produce robust photon sources. In this context, semiconductor quantum dots hold great potential, due to their exceptional photophysical properties and on‐demand operating nature. Concerning the scalability aspect of semiconductor quantum dots, it is advantageous to develop a simple, yet robust method to generate photon states from it. Chirped pulse excitation has been widely demonstrated as a robust and efficient state preparation scheme in quantum dots, thereby boosting its applicability as a stable photon source in a real‐world scenario. Despite the rapid growth and advancements in laser technologies, the generation and control of chirped laser pulses can be demanding. Here, an overview of a selected few approaches is presented to tailor and characterize chirped pulses for the efficient excitation of a quantum dot source. By taking the chirped‐pulse‐induced adiabatic rapid passage process in quantum dot as an example, numerical design examples are presented along with experimental advantages and challenges in each method and conclude with an outlook on future perspectives.
Judging the relative trustworthiness of research results: How to do it and why it matters
Authors: Gorard Stephen
Published: January 2024

This paper describes, and lays out an argument for, the use of a procedure to help groups of reviewers to judge the quality of prior research reports. It argues why such a procedure is needed, and how other existing approaches are only relevant to some kinds of research, meaning that a review or synthesis cannot successfully combine quality judgements of different types of research. The proposed procedure is based on four main factors: the fit between the research question(s) for any study and its design(s); the size of the smallest group of cases used in the headline analyses; the amount and skewness of missing data; and the quality of the data collected. This simple procedure is now relatively widely used, and has been found to lead to widespread agreement between reviewers. It can fundamentally change the findings of a review of evidence, compared to the conclusions that would emerge from a more traditional review that did not include genuine quality rating of prior evidence. And powerfully, because it is not technical, it permits users to help judge research findings. This is important as there is a growing demand for evidence‐led approaches in areas of social science such as education, wherein summaries of evidence must be as trustworthy as possible.
An interaction of patriarchy and female leadership: A synthesis of literature on women leadership in Eswatini
Authors: Nkambule Happy , Perumal Juliet
Published: January 2024

This paper presents results of a systematic research synthesis of 23 studies on female leadership in Eswatini. The review aimed to present conclusions drawn from synthesising findings from studies on women's participation in leadership in Eswatini. Systematic methods were used in the review to identify the 23 research studies focusing on female leadership across sectors in Eswatini. Since the reviewed studies were qualitative, research synthesis methods were used, and three main themes were identified across the excavated studies. The three main themes are: (1) gender inequality, (2) challenges for women leadership, and (3) women empowerment. Sub‐themes relating to the main themes also emerged. Challenges highlighted were categorised into two: those inhibiting access to leadership for women, and those affecting women who are already in leadership. Forms of women empowerment discussed in the studies are: in‐service training, networking and mentoring. The analysis contributed to knowledge on female leadership in Eswatini by highlighting contributions and limitations of these studies, and further provides a base for future conceptual analysis.

Context and implications

Rationale for the study

The main purpose for undertaking the synthesis of literature on women leadership in Eswatini was to add a voice in the leadership discourse using Eswatini's context.

Why the new findings matter

The review on women leadership in Eswatini contributes to the knowledge on African women leadership, and further act as a signpost for future research.

Implications for practioners

The synthesis revealed the dearth of literature on female leadership in Eswatini, thus highlighting the need for scholars and feminist researchers to prioritise documenting the voices of women leaders that remains undocumented, so that upcoming young leaders can learn from the great works done by those who have walked uncharted paths before them.
Group consensus tracking of second‐order nonlinear multi‐agent systems with time‐varying reference velocities
Authors: Yu Junyan , Li Yajie
Published: January 2024

This paper investigates group consensus tracking problems with time‐varying reference velocities. The multiple agents are described as second‐order nonlinear dynamics in directed information exchange settings. For the multi‐agent networks formed by finite agent groups, novel distributed protocols with/without time‐varying transmission delays are designed to solve the group consensus tracking problems. The problems are first transformed into the asymptotical stability of consensus error systems and the input‐to‐state stability of tracking error systems, and then sufficient conditions are derived to guarantee the agents realizing the group consensus tracking based on Lyapunov stability theories. Finally, several simulations are given to verify the effectiveness of the theoretical results.
An event‐triggered subspace predictive control method for partially unknown linear parameter‐varying systems
Authors: Li Zhe , Liu Kexin , Wang Xudong , Yuan Xiaofang , Liu Yubai , Wang Yaonan
Published: January 2024

This article develops a novel event‐triggered subspace predictive control (ET‐SPC) method for discrete‐time linear parameter‐varying (LPV) systems with partially unknown system parameters. An event‐triggered law is developed to alleviate the heavy load of data transmission and computation in the conventional subspace predictive control methods for the LPV systems. The design of the event‐triggered law relies on the input‐to‐state stability (ISS) theory and applies the robust stability condition based on linear matrix inequalities (LMIs), which guarantees the stability of the proposed method. Consequently, the input component can be directly transmitted to the system without receding horizon optimization when the event‐triggered law evaluates that the system satisfies the stability condition. The simulation results illustrate its satisfactory performance, which indicates its potential application involving a considerable amount of data transmission and computation such as the network control systems (NCSs).
CEO attention and sustainable development: An analysis of its influence on firm's sustainability orientation
Authors: Yu Kangkang , Hou Shaobo , Qian Cheng , Zhang Lingbo
Published: January 2024

Drawing on the attention‐based view and leadership theory, this study proposes a theoretical framework for the relationship between CEOs' attention load and firms' sustainability orientation, with supply chain leadership and CEOs' social capital playing mediating and moderating roles, respectively. We tested the theoretical framework by analysing panel data on 236 CEOs from 102 listed companies in the agricultural and food industries in China from 2012 to 2019. We find that (a) CEOs' attention load negatively affects firms' sustainable orientation; (b) this relationship is partially mediated by firms' supply chain leadership; and (c) CEOs' social capital positively moderates this mediating effect. Lower CEO attention loads are associated with increased supply chain leadership and higher sustainability orientation for the firm. Additionally, CEOs' social capital positively moderates the relationship between attention load and sustainability orientation. This study integrates the attention‐based view and leadership theory into sustainable development research, investigating the translation mechanism of CEO attention to a firm's managerial orientation towards sustainability. It contributes to leadership theory by extending sustainable and ethical leadership from an intra‐ to inter‐organisational context.
2D Film‐Like Magnetic SERS Tag with Enhanced Capture and Detection Abilities for Immunochromatographic Diagnosis of Multiple Bacteria
Authors: Li Jiaxuan , Shen Wanzhu , Liang Xueyan , Zheng Shuai , Yu Qing , Wang Chaoguang , Wang Chongwen , Gu Bing
Published: January 2024

Here, a multiplex surface‐enhanced Raman scattering (SERS)–immunochromatography (ICA) platform is presented using a graphene oxide (GO)‐based film‐like magnetic tag (GFe–DAu–D/M) that effectively captures and detects multiple bacteria in complex specimens. The 2D GFe–DAu–D/M tag with universal bacterial capture ability is fabricated through the layer‐by‐layer assembly of one layer of small Fe3O4 nanoparticles (NPs) and two layers of 30 nm AuNPs with a 0.5 nm built‐in nanogap on monolayer GO nanosheets followed by co‐modification with 4‐mercaptophenylboronic acid (MPBA) and 5,5′‐dithiobis‐(2‐nitrobenzoic acid).The GFe–DAu–D/M enabled the rapid enrichment of multiple bacteria by MPBA and quantitative analysis of target bacteria on test lines by specific antibodies, thus achieving multiple signal amplification of magnetic enrichment effect and multilayer dense hotspots and eliminating matrix interference in real‐world applications. The developed technology can directly and simultaneously diagnose three major pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella typhimurium) with detection limits down to the level of 10 cells mL−1. The good performance of the proposed method in the detection of real urinary tract infection specimens is also demonstrated, suggesting the great potential of the GFe–DAu–D/M–ICA platform for the highly sensitive monitoring of bacterial infections or contamination.
Decoding the “Fingerprint” of Implant Materials: Insights into the Foreign Body Reaction
Authors: Chen Yangmengfan , Luo Zeyu , Meng Weikun , Liu Kai , Chen Qiqing , Cai Yongrui , Ding Zichuan , Huang Chao , Zhou Zongke , Jiang Meng , Zhou Liqiang
Published: January 2024

Foreign body reaction (FBR) is a prevalent yet often overlooked pathological phenomenon, particularly within the field of biomedical implantation. The presence of FBR poses a heavy burden on both the medical and socioeconomic systems. This review seeks to elucidate the protein “fingerprint” of implant materials, which is generated by the physiochemical properties of the implant materials themselves. In this review, the activity of macrophages, the formation of foreign body giant cells (FBGCs), and the development of fibrosis capsules in the context of FBR are introduced. Additionally, the relationship between various implant materials and FBR is elucidated in detail, as is an overview of the existing approaches and technologies employed to alleviate FBR. Finally, the significance of implant components (metallic materials and non‐metallic materials), surface CHEMISTRY (charge and wettability), and physical characteristics (topography, roughness, and stiffness) in establishing the protein “fingerprint” of implant materials is also well documented. In conclusion, this review aims to emphasize the importance of FBR on implant materials and provides the current perspectives and approaches in developing implant materials with anti‐FBR properties.
Suppressing Redox Reactions at the Perovskite‐Nickel Oxide Interface with Zinc Nitride to Improve the Performance of Perovskite Solar Cells
Authors: Mann Dilpreet Singh , Kwon Sung‐Nam , Thakur Sakshi , Patil Pramila , Jeong Kwang‐Un , Na Seok‐In
Published: January 2024

For p‐i‐n perovskite solar cells (PSCs), nickel oxide (NiOx) hole transport layers (HTLs) are the preferred interfacial layer due to their low cost, high mobility, high transmittance, and stability. However, the redox reaction between the Ni≥3+ and hydroxyl groups in the NiOx and perovskite layer leads to oxidized CH3NH3+ and reacts with PbI in the perovskite, resulting in a large number of non‐radiative recombination sites. Among various transition metals, an ultra‐thin zinc nitride (Zn3N2) layer on the NiOx surface is chosen to prevent these redox reactions and interfacial issues using a simple solution process at low temperatures. The redox reaction and non‐radiative recombination at the interface of the perovskite and NiOx reduce chemically by using interface modifier Zn3N2 to reduce hydroxyl group and defects on the surface of NiOx. A thin layer of Zn3N2 at the NiOx/perovskite interface results in a high Ni3+/Ni2+ ratio and a significant work function (WF), which inhibits the redox reaction and provides a highly aligned energy level with perovskite crystal and rigorous trap‐passivation ability. Consequently, Zn3N2‐modified NiOx‐based PSCs achieve a champion PCE of 21.61%, over the NiOx‐based PSCs. After Zn3N2 modification, the PSC can improve stability under several conditions.
Gas Therapy: Generating, Delivery, and Biomedical Applications
Authors: Ghaffari‐Bohlouli Pejman , Jafari Hafez , Okoro Oseweuba Valentine , Alimoradi Houman , Nie Lei , Jiang Guohua , Kakkar Ashok , Shavandi Amin
Published: January 2024

Oxygen (O2), nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), and hydrogen (H2) with direct effects, and carbon dioxide (CO2) with complementary effects on the condition of various diseases are known as therapeutic gases. The targeted delivery and in situ generation of these therapeutic gases with controllable release at the site of disease has attracted attention to avoid the risk of gas poisoning and improve their performance in treating various diseases such as cancer therapy, cardiovascular therapy, bone tissue engineering, and wound healing. Stimuli‐responsive gas‐generating sources and delivery systems based on biomaterials that enable on‐demand and controllable release are promising approaches for precise gas therapy. This work highlights current advances in the design and development of new approaches and systems to generate and deliver therapeutic gases at the site of disease with on‐demand release behavior. The performance of the delivered gases in various biomedical applications is then discussed.
Investigation on Recrystallization Behavior of Cold‐Rolled Silicon Steel in Continuous Heating with Three‐Point Bending Testing
Authors: Liu Yameng , Fang Xianshi , Liu Kaixin , Wang Zhilei , Zhang Zhihao , Liu Xinhua
Published: January 2024

Understanding the recrystallization behavior of cold‐rolled silicon steel during continuous heating is essential for optimizing continuous annealing parameters and accurately controlling material performance. To address the limitations of isothermal annealing studies in interpreting actual continuous annealing processes, this study investigates the recrystallization kinetics of Fe–2.3 wt%Si steel using a continuous heating three‐point bending method. The method effectively determines the characteristic recrystallization temperatures. Interestingly, these recrystallization characteristic temperatures remain unaffected by the initial load but shift toward higher temperatures with increasing heating rates in the range of 5–15 °C min−1. The average activation energy of recrystallization is estimated to be 144.5 kJ mol−1, comparable to the value of 147.0 kJ mol−1 obtained from the isothermal process through microhardness measurement. The recrystallization kinetics, described by an extended version of the Ozawa–Flynn–Wall model, exhibits excellent agreement with experimental evaluations. By combining the present processing technologies with continuous heating recrystallization kinetics, different recrystallization temperatures and times can be determined, offering valuable insights for optimizing annealing processes.
Coordinated Q‐V/P‐f Control Strategy Using Virtual Power Factor for Autonomous AC Microgrid with PV Smart Inverters
Authors: Arou Anyuat John , Tsuji Takao
Published: January 2024

Given the increasing interests in carbon neutrality due to climate change, photovoltaic (PV)‐based microgrid has become an important research topic worldwide. Typically, high PV penetration without proper control schemes causes power quality issues such as voltage or frequency violation, resulting in the limited PV hosting capacity. Reactive and active power support from the PV is effective to solve the issues, however, it is a critical challenge to efficiently contribute to the stabilizing controls under the inverter capacity constraint. Recent studies have applied smart inverters, equipped with fixed active and reactive power control reserves, for dynamic voltage and frequency support. In this paper, we proposed a control strategy in which the control reserves for voltage and frequency support are flexibly adjusted using virtual power factor (VPF) to improve the power quality with reducing active power curtailment. The effectiveness of the proposed Q‐V/P‐f control is verified through numerical simulations using a microgrid model developed in MATLAB/Simulink platform. It was observed through the simulation that the proposed method contributed to mitigating voltage and frequency fluctuation with satisfying the inverter capacity constraint. © 2024 Institute of Electrical Engineer of Japan and Wiley Periodicals LLC.
Therapeutic management of metabolic dysfunction associated steatotic liver disease
Authors: Zeng Jing , Fan Jian‐Gao , Francque Sven M.
Published: January 2024

The incidence and prevalence of non‐alcoholic fatty liver disease (NAFLD) have been steadily increasing worldwide, with a huge societal and economic burden. Recently, NAFLD and non‐alcoholic steatohepatitis have been renamed and redefined as metabolic dysfunction associated steatotic liver disease (MASLD) and steatohepatitis (Metabolic Dysfunction Associated Steatohepatitis (MASH)), which result from an imbalance between metabolic and inflammatory stress (mainly as a consequence of adipose tissue dysfunction and insulin resistance) and the defence and repair mechanisms of the steatotic liver. Once MASLD progresses to end‐stage of liver disease, treatment efficacy becomes limited and may require liver transplantation. Early detection and intervention are crucial. Lifestyle modification is consequently the cornerstone of its management. Timely consideration of bariatric surgeries should be given to patients meeting specific criteria. A multidisciplinary approach is warranted, starting from the concept that MASLD/MASH is at the centre of the cardiovascular‐liver‐metabolic syndrome. In some cases, pharmacological treatment can complement lifestyle modification. Several drugs used to treat the cardiometabolic co‐morbidities have some potential efficacy in slowing Down disease progression, and some have demonstrated efficacy on histological endpoints that are likely to translate into long‐term clinical benefits. Optimising the use of these drugs within their licenced indications is thus paramount for patients with MASLD. Several MASH‐specific drugs are on the horizon and are likely to enrich our therapeutic armamentarium in the near future, particularly in non‐cirrhotic stages of the disease. Much work still needs to be done to understand the specific features of MASH cirrhosis and develop efficacious treatments for this disease stage.
Single‐port robotic subcostal major pulmonary resection using the single‐port robotic system
Authors: Lee Jun Hee , Hong Jeong In , Kim Hyun Koo
Published: January 2024

Background

The da Vinci single‐port system (SPS) (Intuitive Surgical, Sunnyvale, CA, USA) was designed for single‐port (SP) surgery. Although we have reported our clinical outcomes using the SPS for a simple procedure in general thoracic surgery, major pulmonary resection had been performed only in cadaveric experiments to date. This study evaluated the feasibility of SP subcostal robotic major pulmonary resection using the SPS. Here, we present our initial clinical experience of SP subcostal robotic major pulmonary resection at our institution.

Methods

Twenty‐five patients with lung cancer underwent SP major subcostal pulmonary resection using the SPS between March and November 2022. Patient characteristics, intraoperative and perioperative outcomes were assessed. Questionnaires were used to evaluate patient satisfaction with the cosmetic results and quality of life through face‐to‐face or telephone interviews on postoperative day 30.

Results

All patients underwent major pulmonary resection with complete radical resection (R0). Nineteen patients underwent lobectomy, whereas six patients underwent segmentectomy. The mean docking time and total operative time were 4.16 ± 1.19 min (range, 2.3–7.8 min) and 197.6 ± 55.33 min (range, 130–313 min), respectively. No patients underwent conversion to open thoracotomy. One patient required an additional assistant port due to severe pleural adhesions.

Conclusions

SP subcostal robotic major pulmonary resection using the SPS is feasible and safe. With the continuous development of robotic technology and surgical techniques, we believe that more complex general thoracic surgeries will be performed in the future using SPS.
The Role of Fundamental Modeling
Authors: Sandström Rolf
Published: January 2024

The difference between empirical and basic modeling and its significance is explained. The types of basic models that have been possible to develop and that are describe in the book are summarized. The starting point is a basic model for the dislocation density that is used to derive expression for tensile and creep properties. It is described how the accuracy of the basic models can be verified. For the creep models it is described that they are applicable over a wide range of temperatures and stresses that is of great value to identify operating mechanisms.
Cavitation
Authors: Sandström Rolf
Published: January 2024

Cavitation is of great technical importance. Nucleated cavities grow and link to form cracks that can cause rupture. During creep, cavities are initiated in the grain boundaries. The nucleation takes place at particles or at subboundary—grain boundary junctions. The main mechanism is believed to be grain boundary sliding (GBS), Chap. 9. According to the double ledge model, cavities are formed when the particles or subboundaries meet other subboundaries. With this assumption quantitative models for cavity nucleation can be derived. They show that the nucleated number of cavities is proportional to the creep strain in good accordance with observations. Cavities can grow by diffusion or by straining. It is important to take into account that cavities cannot grow faster than the surrounding creeping matrix, which is referred to as constrained growth. Otherwise the growth rate can be significantly overestimated. Models both for diffusion and strain controlled growth have been available for a long time. A recently developed model for strain controlled growth is presented based on GBS. It has the advantage that is associated with a well-defined initiation size of cavities and that constrained growth is automatically taken into account, features that some previous strain controlled models miss.
Creep Ductility
Authors: Sandström Rolf
Published: January 2024

For a number of creep resistant steels, the creep ductiliy decreases with increasing temperature and time. As a function of stress, the ductiity is often describe with an S-shaped curve with an upper and a lower shelf level. As a function of time, the S-shape is inverted. If the ductility is high, the rupture is referred to as ductile, and for low ductility levels as brittle. Ductile rupture is believed to be due to a plastic instability such as necking. Brittle rupture on the other hand is controlled by the nucleation, growth and linkage of creep cavities. With the help of the basic models for creep deformation and cavitation, the rupture stress and ductility can be predicted. Several models exist for the influence of multiaxiality on the creep ductility. Although the models are based on different principles, they predict approximately the same behavior, which is verified by comparison to rupture data for notched bars.
How do schools influence the emotional and behavioural health of their pupils? A multi-level analysis of 135 schools in the Born in Bradford inner city multi-ethnic birth cohort
Authors: Lewer Dan , Gilbody Simon , Lewis Gemma , Pryce Joseph , Santorelli Gillian , Wadman Ruth , Watmuff Aidan , Wright John
Published: January 2024

Purpose

To estimate variation in emotional and behavioural problems between primary schools in Bradford, an ethnically diverse and relatively deprived city in the UK.

Methods

We did a cross-sectional analysis of data collected from 2017 to 2021 as part of the ‘Born In Bradford’ birth cohort study. We used multilevel linear regression in which the dependent variable was the Strengths and Difficulties Questionnaire (SDQ) total score, with a random intercept for schools. We adjusted for pupil-level characteristics including age, ethnicity, socioeconomic status, and parental mental health.

Results

The study included 5,036 participants from 135 schools. Participants were aged 7–11 years and 56% were of Pakistani heritage. The mean SDQ score was 8.84 out of a maximum 40. We estimated that the standard deviation in school-level scores was 1.41 (95% CI 1.11–1.74) and 5.49% (95% CI 3.19–9.37%) of variation was explained at school level. After adjusting for pupil characteristics, the standard deviation of school-level scores was 1.04 (95% CI 0.76–1.32) and 3.51% (95% CI 1.75–6.18%) of variation was explained at school level. Simulation suggested that a primary school with 396 pupils at the middle of the distribution has 63 pupils (95% CI 49–78) with a ‘raised’ SDQ score of 15 + /40; and shifting a school from the lower to the upper quartile would prevent 26 cases (95% CI 5–46).

Conclusion

The prevalence of emotional and behavioural problems varies between schools. This is partially explained by pupil characteristics; though residual variation in adjusted scores may suggest that schools have a differential impact on mental wellbeing.
Milk microbiome transplantation: recolonizing donor milk with mother's own milk microbiota
Authors: Stinson Lisa F. , Ma Jie , Lai Ching Tat , Rea Alethea , Perrella Sharon L. , Geddes Donna T.
Published: January 2024

Donor human milk (DHM) provides myriad nutritional and immunological benefits for preterm and low birthweight infants. However, pasteurization leaves DHM devoid of potentially beneficial milk microbiota. In the present study, we performed milk microbiome transplantation from freshly collected mother’s own milk (MOM) into pasteurized DHM. Small volumes of MOM (5%, 10%, or 30% v/v) were inoculated into pasteurized DHM and incubated at 37 °C for up to 8 h. Further, we compared microbiome recolonization in UV-C-treated and Holder-pasteurized DHM, as UV-C treatment has been shown to conserve important biochemical components of DHM that are lost during Holder pasteurization. Bacterial culture and viability-coupled metataxonomic sequencing were employed to assess the effectiveness of milk microbiome transplantation. Growth of transplanted MOM bacteria occurred rapidly in recolonized DHM samples; however, a greater level of growth was observed in Holder-pasteurized DHM compared to UV-C-treated DHM, potentially due to the conserved antimicrobial properties in UV-C-treated DHM. Viability-coupled metataxonomic analysis demonstrated similarity between recolonized DHM samples and fresh MOM samples, suggesting that the milk microbiome can be successfully transplanted into pasteurized DHM. These results highlight the potential of MOM microbiota transplantation to restore the microbial composition of UV-C-treated and Holder-pasteurized DHM and enhance the nutritional and immunological benefits of DHM for preterm and vulnerable infants.

Key points

• Mother’s own milk microbiome can be successfully transplanted into donor human milk.

• Recolonization is equally successful in UV-C-treated and Holder-pasteurized milk.

• Recolonization time should be restricted due to rapid bacterial growth.

Graphical Abstract
Association between vitamin D status, physical performance, sex, and lifestyle factors: a cross-sectional study of community-dwelling Kosovar adults aged 40 years and older
Authors: Krasniqi Ermira , Boshnjaku Arben , Ukëhaxhaj Antigona , Wagner Karl-Heinz , Wessner Barbara
Published: January 2024

Purpose

Vitamin D status and its association with age-related decline in physical performance and strength have already been highlighted in various ways, but data on the situation in developing countries are scarce. This study aimed to investigate vitamin D status, its association with muscle mass and function, and other potential determinants such as age, sex, lifestyle factors (physical activity, dietary behavior), self-perceived health status, medication intake, education and financial situation in adults from Kosovo.

Methods

This cross-sectional study included 297 participants (54.5% women), aged ≥ 40 years. Serum 25-hydroxyvitamin D (25(OH)D) concentration, hand grip strength and physical performance tests, body composition, vitamin D dietary intake and knowledge were assessed. The interaction between serum 25(OH)D status, lifestyle factors and muscle traits was investigated.

Results

Vitamin D deficiency (< 50 nmol/L) was observed in 47.5% of the total population, of whom 14.7% of them were severely deficient (< 30 nmol/L). No associations were found between 25(OH)D concentration and age. Daily dietary intake of vitamin D was low (1.89 ± 0.67 µg) and 87.6% of individuals did not take vitamin D supplements. However, vitamin D supplementation was the only variable that added statistical significance (p < 0.05) to the prediction of vitamin D status (3.8%). On the other hand, age, medication intake and vitamin D level contributed significantly to the overall regression model, explaining 24.9% of the 30-s chair stand performance as an indicator of lower-body strength endurance.

Conclusion

Vitamin D deficiency is highly prevalent among community-dwelling adults in Kosovo and low serum 25(OH)D has been associated with low muscle strength. This implies an urgent need for the development of comprehensive prevention strategies, focusing on pharmacological (supplementation) but also on non-pharmacological strategies such as education, food fortification or lifestyle advices.
Novel functions of the anion exchanger AE4 (SLC4A9)
Authors: Vitzthum Helga , Meyer-Schwesinger Catherine , Ehmke Heimo
Published: January 2024

The kidney plays a crucial role in acid-base homeostasis. In the distal nephron, α-intercalated cells contribute to urinary acid (H+) secretion and β-intercalated cells accomplish urinary base (HCO3-) secretion. β-intercalated cells regulate the acid base status through modulation of the apical Cl-/HCO3- exchanger pendrin (SLC26A4) activity. In this review, we summarize and discuss our current knowledge of the physiological role of the renal transporter AE4 (SLC4A9). The AE4, as cation-dependent Cl-/HCO3- exchanger, is exclusively expressed in the basolateral membrane of β-intercalated cells and is essential for the sensing of metabolic acid-base disturbances in mice, but not for renal sodium reabsorption and plasma volume control. Potential intracellular signaling pathways are discussed that might link basolateral acid-base sensing through the AE4 to apical pendrin activity.
Plasma cell-free DNA as a sensitive biomarker for multi-cancer detection and immunotherapy outcomes prediction
Authors: Xu Juqing , Chen Haiming , Fan Weifei , Qiu Mantang , Feng Jifeng
Published: January 2024

Background

Cell-free DNA (cfDNA) has shown promise in detecting various cancers, but the diagnostic performance of cfDNA end motifs for multiple cancer types requires verification. This study aimed to assess the utility of cfDNA end motifs for multi-cancer detection.

Methods

This study included 206 participants: 106 individuals with cancer, representing 20 cancer types, and 100 healthy individuals. The participants were divided into training and testing cohorts. All plasma cfDNA samples were profiled by whole-genome sequencing. A random forest model was constructed using cfDNA 4 bp-end-motif profiles to predict cancer in the training cohort, and its performance was evaluated in the testing cohort. Additionally, a separate random forest model was developed to predict immunotherapy responses.

Results

In the training cohort, the model based on 4 bp-end-motif profiles achieved an AUC of 0.962 (95% CI 0.936–0.987). The AUC in the testing cohort was 0.983 (95% CI 0.960–1.000). The model also maintained excellent predictive ability in different tumor sub-cohorts, including lung cancer (AUC 0.918, 95% CI 0.862–0.974), gastrointestinal cancer (AUC 0.966, 95% CI 0.938–0.993), and other cancer cohort (AUC 0.859, 95% CI 0.776–0.942). Moreover, the model utilizing 4 bp-end-motif profiles exhibited sensitivity in identifying responders to immunotherapy (AUC 0.784, 95% CI 0.609–0.960).

Conclusion

The model based on 4 bp-end-motif profiles demonstrates superior sensitivity in multi-cancer detection. Detection of 4 bp-end-motif profiles may serve as potential predictive biomarkers for cancer immunotherapy.
Der Schmerz und seine Grenze
Authors: Wagner Judith N.
Published: January 2024

Chronische Schmerzen stellen weltweit ein signifikantes sozialmedizinisches Problem mit hohen Folgekosten dar. Als eigenständige Erkrankung werden Schmerzsyndrome jedoch erst seit etwa Mitte des 20. Jahrhunderts angesehen. Schon in der Definition der International Association for the Study of Pain wird deutlich, dass Schmerz ein komplexes, kontextabhängiges, damit aber auch modifizierbares Phänomen darstellt. Die philosophische Herangehensweise an den Schmerz ist mindestens ebenso facettenreich und kann unter den verschiedensten Gesichtspunkten erfolgen. Im Folgenden soll eine Charakterisierung des Schmerzes unter Einbeziehung einer philosophischen – phänomenologisch und enaktivistisch geprägten – Perspektive angestrebt werden. Als Leitstruktur dieser Betrachtung soll das Konzept der leiblichen Grenze dienen: In welcher Beziehung stehen Schmerz und die Wahrnehmung der Leibesgrenzen zueinander? Handelt es sich um eine wechselseitige Einflussnahme? Und ist diese Wahrnehmung zugunsten des Schmerzpatienten modifizierbar? Anhand dieser Überlegungen wird auch deutlich werden, dass die beiden Wissenschaften – Neurowissenschaften und Philosophie – mitnichten Konkurrentinnen darstellen, sondern vielmehr Disziplinen, die sich gegenseitig informieren.
Efbemalenograstim alfa not inferior to pegfilgrastim in providing neutrophil support in women with breast cancer undergoing myelotoxic chemotherapy: results of a phase 2 randomized, multicenter, open-label trial
Authors: Glaspy John , Bondarenko Igor , Krasnozhon Dmitrii , Rutty Dean , Chen Jianmin , Fu Yanyan , Wang Shufang , Hou Qingsong , Li Simon
Published: January 2024

Purpose

Evaluate the safety and efficacy of efbemalenograstim alfa for neutrophil support in breast cancer patients undergoing myelosuppressive chemotherapy in a phase 2, dose-finding, open-label study (NCT01648322, ClinicalTrials.gov, 2012–07-19).

Methods

232 patients received up to 4 cycles of chemotherapy, 141 patients with docetaxel + cyclophosphamide (TC) and 91 patients with docetaxel + doxorubicin + cyclophosphamide (TAC). Patients were randomized to efbemalenograstim alfa (80, 240, or 320 µg/kg [TC]; 240 or 320 µg/kg [TAC]) or pegfilgrastim (6 mg) on Day 2 of each cycle.

Results

Efbemalenograstim alfa was non-inferior to pegfilgrastim in duration of moderate and severe neutropenia (absolute neutrophil count [ANC] < 1.0 × 109/L) in TAC Cycle 1 (mean [SD] of 2.1 [1.58] and 2.1 [1.46] days for 240 µg/kg and 320 µg/kg efbemalenograstim alfa, respectively, and 1.8 [1.28] days for pegfilgrastim), with a difference (95% CI) of 0.3 (-0.4, 1.1) days. ANC nadir occurred between Days 7–8 of TAC Cycle 1, with mean [SD] of 0.68 [1.064], 0.86 [1.407] and 0.78[1.283] × 109/L for 240 µg/kg, 320 µg/kg efbemalenograstim alfa and pegfilgrastim, respectively. Time to ANC recovery post nadir (defined as an ANC > 2.0 × 109/L after the expected ANC nadir) was 2.0–2.4 and 1.9 days for TAC patients treated with efbemalenograstim alfa and pegfilgrastim, respectively. No significant difference was found between any dose of efbemalenograstim alfa and pegfilgrastim in TAC Cycle 1 for incidence of moderate to severe neutropenia (76%-77% of patients) or incidence of severe neutropenia (ANC < 0.5 × 109/L; 63%-72%). Efbemalenograstim alfa exhibited similar safety profile to pegfilgrastim. Febrile neutropenia occurred in 4 (1.8%) patients, 2 patients each for 320 µg/kg efbemalenograstim alfa and pegfilgrastim, with no event considered related to study drug.

Conclusion

Efbemalenograstim alfa was comparable to pegfilgrastim in efficacy and safety.

ClinicalTrials.gov identifier

NCT01648322.
Quality of life following treatment with intra-arterial cisplatin with concurrent radiation and erlotinib for locally advanced head and neck cancer
Authors: Cossyleon Ricardo , Robinson Kathy , Delfino Kristin , Robbins K. Thomas , Rao Krishna
Published: January 2024

Objectives

Studies that focus on the feasibility of using erlotinib plus chemoradiation to treat locally advanced head and neck cancer have given hints of improved survival outcomes compared to chemoradiation alone. However, the influence of this treatment regimen on the quality of life of the patients has not been documented. We conducted a study of this triple combination and now have documented follow-up survival data as well as long-term quality of life (QoL) measures.

Methods

Three sets of QoL questionnaires were given to patients with a diagnosis of head and neck cancer at two time points, pre- and post-treatment, to assess differences in quality of life after receiving chemotherapy with intra-arterial (IA) cisplatin (150 mg/m2), concomitant radiation (70 Gy), and oral erlotinib (150 mg/day). Additionally, patients were followed for a total of 5 years.

Results

Treatment had a detrimental effect on appearance, taste, and saliva domain scores in their QoL questionnaires. Nonetheless, fewer patients reported pain and anxiety.

Significance of results

The combination of erlotinib with chemoradiation produced similar adverse effects on the QoL scores of patients with head and neck cancer as compared to chemoradiation alone.
Electrochemical solid phase formation and dissolution; a non-equilibrium thermodynamic view
Authors: Malaie Keyvan
Published: January 2024

Herein, solid-state electrochemical reactions are collectively viewed and studied as the formation and dissolution of a solid phase under non-equilibrium. We first consider an ideal reaction pathway where a solid phase grows and shrinks along the same reaction path. Next, the realistic situation is studied based on the voltammetry of solids to reveal how a solid phase is formed and dissolved in contact with either a liquid or another solid phase. Finally, the reaction asymmetry between phase formation and dissolution, hysteresis, and the memory effect are studied and discussed in detail.
Evaluation of polycyclic aromatic hydrocarbon contents in marine products in South Korea and risk assessment using the total diet study
Authors: Paik Yujin , Kim Hoe-Sung , Joo Yong-Sung , Lee Jin Won , Lee Kwang-Won
Published: January 2024

This study investigated levels of eight polycyclic aromatic hydrocarbons (PAH8) compounds in both raw and processed marine products in South Korea. Katsuobushi exhibited the highest concentration of benzo[a]pyrene, at 14.22 µg/kg, exceeding the European Commission's regulation level of 5.0 µg/kg. The total PAH8 concentration in katsuobushi was 220.5 µg/kg. Among the product categories, shellfish had the highest detection rate (70%), followed by fish (19%) and crustacea (8%), with chrysene being the most prominent PAH8 congener in all marine products. Grilled fish predominantly contained pyrogenic PAHs from combustion byproducts, while shellfish primarily contained petrogenic ones from the aquatic environment. Grilling, smoking, and drying processes significantly contributed to the formation of PAH8 in these food products. Based on the results of a risk assessment using a margin of exposure approach through a total diet study, exposure to PAH8 from marine products is considered to pose low concern to the South Korean population.
A voting gray wolf optimizer-based ensemble learning models for intrusion detection in the Internet of Things
Authors: Saheed Yakub Kayode , Misra Sanjay
Published: January 2024

The Internet of Things (IoT) has garnered considerable attention from academic and industrial circles as a pivotal technology in recent years. The escalation of security risks is observed to be associated with the growing interest in IoT applications. Intrusion detection systems (IDS) have been devised as viable instruments for identifying and averting malicious actions in this context. Several techniques described in academic papers are thought to be very accurate, but they cannot be used in the real world because the datasets used to build and test the models do not accurately reflect and simulate the IoT network. Existing methods, on the other hand, deal with these issues, but they are not good enough for commercial use because of their lack of precision, low detection rate, receiver operating characteristic (ROC), and false acceptance rate (FAR). The effectiveness of these solutions is predominantly dependent on individual learners and is consequently influenced by the inherent limitations of each learning algorithm. This study introduces a new approach for detecting intrusion attacks in an IoT network, which involves the use of an ensemble learning technique based on gray wolf optimizer (GWO). The novelty of this study lies in the proposed voting gray wolf optimizer (GWO) ensemble model, which incorporates two crucial components: a traffic analyzer and a classification phase engine. The model employs a voting technique to combine the probability averages of the base learners. Secondly, the combination of feature selection and feature extraction techniques is to reduce dimensionality. Thirdly, the utilization of GWO is employed to optimize the parameters of ensemble models. Similarly, the approach employs the most authentic intrusion detection datasets that are accessible and amalgamates multiple learners to generate ensemble learners. The hybridization of information gain (IG) and principal component analysis (PCA) was employed to reduce dimensionality. The study utilized a novel GWO ensemble learning approach that incorporated a decision tree, random forest, K-nearest neighbor, and multilayer perceptron for classification. To evaluate the efficacy of the proposed model, two authentic datasets, namely, BoT-IoT and UNSW-NB15, were scrutinized. The GWO-optimized ensemble model demonstrates superior accuracy when compared to other machine learning-based and deep learning models. Specifically, the model achieves an accuracy rate of 99.98%, a DR of 99.97%, a precision rate of 99.94%, an ROC rate of 99.99%, and an FAR rate of 1.30 on the BoT-IoT dataset. According to the experimental results, the proposed ensemble model optimized by GWO achieved an accuracy of 100%, a DR of 99.9%, a precision of 99.59%, an ROC of 99.40%, and an FAR of 1.5 when tested on the UNSW-NB15 dataset.
UCP2 and pancreatic cancer: conscious uncoupling for therapeutic effect
Authors: Caggiano Emily G. , Taniguchi Cullen M.
Published: January 2024

Pancreatic cancer has an exaggerated dependence on mitochondrial metabolism, but methods to specifically target the mitochondria without off target effects in normal tissues that rely on these organelles is a significant challenge. The mitochondrial uncoupling protein 2 (UCP2) has potential as a cancer-specific drug target, and thus, we will review the known biology of UCP2 and discuss its potential role in the pathobiology and future therapy of pancreatic cancer.