bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients and informal caregivers in the lead: a qualitative study on the experiences of patients, informal caregivers, and healthcare professionals with involvement in treatment, e-health and self-management programs
Authors: Bosveld Matthijs H. , Smits Anne G.M. , Mertens Helena J.M.M. , Zandvoort Michel J.J.M. van , Mook Walther N.K.A. van , Bokhoven Marloes A. van
Published: June 2024

Background

A significant proportion of patients and informal caregivers favor an active role in decisions concerning their health. Simultaneously, governments aim to shift treatment from a professional care setting to a community setting, in light of an ageing population, a decreasing number of health workers and allocation of scarce resources. This transition of care solicits patients’ and informal caregivers’ ability to self-manage. Therefore, the Maastricht University Medical Centre + has established the Academy for Patients and Informal caregivers. The aim is to proactively and professionally support patients and their informal caregivers to enhance their self-management. For that, the Academy offers activities in three categories: (1) instruction of nursing techniques, (2) training of e-health competencies and (3) the provision of self-management programs. Both patients with an episodic care need, as well as patients and informal caregivers with chronic illness, are eligible to participate in the Academy’s activities. However, little is known about the experience of these interventions from the perspective of patients, informal caregivers and healthcare professionals.

Methods

We conducted semi-structured interviews with 15 patients, 8 informal caregivers and 19 health care professionals who either participated in, referred to or received patients from the Academy. Topics revolved around self-management and the Quadruple aim, covering topics such as patient experiences, healthcare costs, health and well-being of the population and improving work life for health professionals. Data were analyzed using thematic analysis.

Results

Patients and caregivers experienced an increase in the ability to manage health needs independently, leading to increased mental well-being and self-efficacy. They felt recognized as partners in care, although managing illness needs came with its own burdens. Health care professionals indicated that they felt assured of the quality, uniformity and availability of activities due to its central organization, with instruction nurses finding greater meaning in their work. On the level of health care systems, participants in this study mentioned a decrease in use of formal healthcare, whilst enabling a more equitable division of care.

Conclusion

Stakeholders’ experiences with the Academy for Patients and Informal caregivers indicate that participation contributes to development of self-management, whilst also improving working conditions, reducing the appeal to formal care and advancing equity in healthcare. The burden for patients and informal caregivers is to be considered in future developments.
Examining the impact of substance use on hospital length of stay in schizophrenia spectrum disorder: a retrospective analysis
Authors: Burrer Achim , Egger Stephan T. , Spiller Tobias R. , Kirschner Matthias , Homan Philipp , Seifritz Erich , Vetter Stefan
Published: June 2024

Background

Among patients diagnosed with schizophrenia, the presence of substance use poses an aggravating comorbidity, exerting a negative impact on the course of the disease, adherence to therapeutic regimens, treatment outcomes, duration of hospital stays, and the frequency of hospitalizations. The primary objective of the present study is to investigate the relationship between comorbid substance use disorders, antipsychotic treatment, and the length of stay in individuals hospitalized for treatment of schizophrenia.

Methods

We conducted a retrospective analysis of electronic health records spanning a 12-month period, specifically focusing on adult patients diagnosed with schizophrenia who were discharged from the University Hospital of Psychiatry Zurich between January and December 2019. We documented the number and types of diagnosed substance use disorder, the antipsychotic treatment, the length of stay, and the number of previous hospitalizations for each patient.

Results

Over a third (n = 328; 37.1%) of patients with schizophrenia had comorbid substance use with cannabis being the most frequent consumed substance. Patients with substance use (either single or multiple) were more frequently hospitalized; those with multiple substance use more frequently than those with a single substance use (F(2, 882) = 69.06; p < 0.001). There were no differences regarding the rate of compulsory admission. Patients with no substance use had a lower HoNOS score at discharge (F(2, 882) = 4.06). Patients with multiple substance use had a shorter length of stay (F(2, 882) = 9.22; p < 0.001), even after adjusting for duration of illness, previous hospitalizations, diagnosis, and antipsychotic treatment.

Conclusions

In patients with schizophrenia, comorbid single or multiple substance use has a relevant negative impact on treatment and thus on the course of disease. Substance use in patients with schizophrenia should therefore receive special attention in order to reduce re-hospitalization rates and improve the clinical outcome.
Validation of the Health Assessment Tool (HAT) based on four aging cohorts from the Swedish National study on Aging and Care
Authors: Abbadi Ahmad , Kokoroskos Emmanouil , Stamets Matthew , Vetrano Davide L. , Orsini Nicola , Elmståhl Sölve , Fagerström Cecilia , Wimo Anders , Sköldunger Anders , Berglund Johan Sanmartin , Olsson Christina B. , Wachtler Caroline , Fratiglioni Laura , Calderón-Larrañaga Amaia
Published: June 2024

Background

As global aging accelerates, routinely assessing the functional status and morbidity burden of older patients becomes paramount. The aim of this study is to assess the validity of the comprehensive clinical and functional Health Assessment Tool (HAT) based on four cohorts of older adults (60 + years) from the Swedish National study on Aging and Care (SNAC) spanning urban, suburban, and rural areas.

Methods

The HAT integrates five health indicators (gait speed, global cognition, number of chronic diseases, and basic and instrumental activities of daily living), providing an individual-level score between 0 and 10. The tool was constructed using nominal response models, first separately for each cohort and then in a harmonized dataset. Outcomes included all-cause mortality over a maximum follow-up of 16 years and unplanned hospital admissions over a maximum of 3 years of follow-up. The predictive capacity was assessed through the area under the curve (AUC) using logistic regressions. For time to death, Cox regressions were performed, and Harrell’s C-indices were reported. Results from the four cohorts were pooled using individual participant data meta-analysis and compared with those from the harmonized dataset.

Results

The HAT demonstrated high predictive capacity across all cohorts as well as in the harmonized dataset. In the harmonized dataset, the AUC was 0.84 (95% CI 0.81–0.87) for 1-year mortality, 0.81 (95% CI 0.80–0.83) for 3-year mortality, 0.80 (95% CI 0.79–0.82) for 5-year mortality, 0.69 (95% CI 0.67–0.70) for 1-year unplanned admissions, and 0.69 (95% CI 0.68–0.70) for 3-year unplanned admissions. The Harrell’s C for time-to-death throughout 16 years of follow-up was 0.75 (95% CI 0.74–0.75).

Conclusions

The HAT is a highly predictive, clinically intuitive, and externally valid instrument with potential for better addressing older adults’ health needs and optimizing risk stratification at the population level.
Comprehensive characterization of B7 family members in breast cancer: B7-H5 switch reverses breast cancer from “immuno-cold” into “immuno-hot” status
Authors: Liu Jiayu , Wang Cenzhu , Jiang Ying , Zhou Yunxu , Chen Lingyan , Qian Zhiwen , Liu Lu , Wu Danping , Zhang Yan
Published: June 2024

The members of the classic B7 family regulate the immune microenvironment of several malignant tumors. However, the potential relationship between the B7 family and the breast cancer (BrCa) tumor immune microenvironment has remained elusive. In the present study, we provide a comprehensive explanation of the expression, clinical significance, mutation, and immune cell infiltration of B7 family molecules in BrCa. First, we recruited 10 patients with BrCa surgery from the Wuxi Maternal and Child Health Hospital and performed single-cell RNA sequencing (scRNA-seq) analysis to investigate the distribution of B7 family members in multiple immune cell subsets. We focused on B7-2, B7-H3, and B7-H5 molecules of the B7 family and constructed tumor microarrays by self-recruiting patients to perform multiple immunohistochemical (mIHC) analyses and study tumor expression of B7-2, B7-H3, B7-H5 and CD8+ immune cell infiltration. B7-H5 displayed a strong correlation with CD8+ immune cell infiltration. In summary, B7-H5 provides a new perspective for the identification of immunothermal subtypes of BrCa and could function as a switch to reverse BrCa from an “immunologically cold” state to an “immunologically hot” state.

Graphical abstract
Serum concentrations of legacy, alternative, and precursor per- and polyfluoroalkyl substances: a descriptive analysis of adult female participants in the MIREC-ENDO study
Authors: Borghese M. M. , Ward A. , MacPherson S. , Manz K. E. , Atlas E. , Fisher M. , Arbuckle T. E. , Braun J. M. , Bouchard M. F. , Ashley-Martin J.
Published: June 2024

Background

Several legacy and emerging per- and polyfluoroalkyl substances (PFAS) have been regulated around the world. There is growing concern over the proliferation of alternative PFAS, as well as PFAS precursors. Biomonitoring data for PFAS are critical for assessing exposure and human health risk.

Methods

We collected serum samples from 289 adult female participants in a 2018–2021 follow-up study of the Maternal-Infant Research on Environmental Chemicals (MIREC) Canadian pregnancy cohort. Samples were analyzed for 40 PFAS using ultra-performance liquid chromatography–tandem mass spectrometry. For those compounds with > 50% detection, as well as the sum of these compounds, we describe serum concentrations and patterns of exposure according to sociodemographic and obstetrical history characteristics.

Results

17 out of 40 PFAS were detected in > 50% of samples with 7 of these detected in > 97% of samples. Median [95th percentile] concentrations (µg/L) were highest for PFOS (1.62 [4.56]), PFOA (0.69 [1.52]), PFNA (0.38 [0.81]), and PFHxS (0.33 [0.92]). Geometric mean concentrations of PFOA and PFHxS were approximately 2-fold lower among those with more children (≥ 3 vs. 1), greater number of children breastfed (≥ 3 vs. ≤ 1), longer lifetime duration of breastfeeding (> 4 years vs. ≤ 9 months), and shorter time since last pregnancy (≤ 4 years vs. > 8 years). We observed similar patterns for PFOS, PFHpS, and the sum of 17 PFAS, though the differences between groups were smaller. Concentrations of PFOA were higher among “White” participants, while concentrations of N-MeFOSE, N-EtFOSE, 7:3 FTCA, and 4:2 FTS were slightly higher among participants reporting a race or ethnicity other than “White”. Concentrations of legacy, alternative, and precursor PFAS were generally similar across levels of age, education, household income, body mass index, and menopausal status.

Conclusions

We report the first Canadian biomonitoring data for several alternative and precursor PFAS. Our findings suggest that exposure to PFAS, including several emerging alternatives, may be widespread. Our results are consistent with previous studies showing that pregnancy and breastfeeding are excretion pathways for PFAS.
Cell surface CD55 traffics to the nucleus leading to cisplatin resistance and stemness by inducing PRC2 and H3K27 trimethylation on chromatin in ovarian cancer
Authors: Bharti Rashmi , Dey Goutam , Khan Debjit , Myers Alex , Huffman Olivia G. , Saygin Caner , Braley Chad , Richards Elliott , Sangwan Naseer , Willard Belinda , Lathia Justin D. , Fox Paul L. , Lin Feng , Jha Babal Kant , Brown J. Mark , Yu Jennifer S. , Dwidar Mohammed , Joehlin-Price Amy , Vargas Roberto , Michener Chad M. , Longworth Michelle S. , Reizes Ofer
Published: June 2024

Background

Platinum resistance is the primary cause of poor survival in ovarian cancer (OC) patients. Targeted therapies and biomarkers of chemoresistance are critical for the treatment of OC patients. Our previous studies identified cell surface CD55, a member of the complement regulatory proteins, drives chemoresistance and maintenance of cancer stem cells (CSCs). CSCs are implicated in tumor recurrence and metastasis in multiple cancers.

Methods

Protein localization assays including immunofluorescence and subcellular fractionation were used to identify CD55 at the cell surface and nucleus of cancer cells. Protein half-life determinations were used to compare cell surface and nuclear CD55 stability. CD55 deletion mutants were generated and introduced into cancer cells to identify the nuclear trafficking code, cisplatin sensitivity, and stem cell frequency that were assayed using in vitro and in vivo models. Detection of CD55 binding proteins was analyzed by immunoprecipitation followed by mass spectrometry. Target pathways activated by CD55 were identified by RNA sequencing.

Results

CD55 localizes to the nucleus of a subset of OC specimens, ascites from chemoresistant patients, and enriched in chemoresistant OC cells. We determined that nuclear CD55 is glycosylated and derived from the cell surface pool of CD55. Nuclear localization is driven by a trafficking code containing the serine/threonine (S/T) domain of CD55. Nuclear CD55 is necessary for cisplatin resistance, stemness, and cell proliferation in OC cells. CD55 S/T domain is necessary for nuclear entry and inducing chemoresistance to cisplatin in both in vitro and in vivo models. Deletion of the CD55 S/T domain is sufficient to sensitize chemoresistant OC cells to cisplatin. In the nucleus, CD55 binds and attenuates the epigenetic regulator and tumor suppressor ZMYND8 with a parallel increase in H3K27 trimethylation and members of the Polycomb Repressive Complex 2.

Conclusions

For the first time, we show CD55 localizes to the nucleus in OC and promotes CSC and chemoresistance. Our studies identify a therapeutic mechanism for treating platinum resistant ovarian cancer by blocking CD55 nuclear entry.
Tumor-specific enhanced NIR-II photoacoustic imaging via photothermal and low-pH coactivated AuNR@PNIPAM-VAA nanogel
Authors: Sun Xiaodong , Li Yujie , Liu Xiaowan , Cui Dandan , Shi Yujiao , Huang Guojia
Published: June 2024

Background

Properly designed second near-infrared (NIR-II) nanoplatform that is responsive tumor microenvironment can intelligently distinguish between normal and cancerous tissues to achieve better targeting efficiency. Conventional photoacoustic nanoprobes are always “on”, and tumor microenvironment-responsive nanoprobe can minimize the influence of endogenous chromophore background signals. Therefore, the development of nanoprobe that can respond to internal tumor microenvironment and external stimulus shows great application potential for the photoacoustic diagnosis of tumor.

Results

In this work, a low-pH-triggered thermal-responsive volume phase transition nanogel gold nanorod@poly(n-isopropylacrylamide)-vinyl acetic acid (AuNR@PNIPAM-VAA) was constructed for photoacoustic detection of tumor. Via an external near-infrared photothermal switch, the absorption of AuNR@PNIPAM-VAA nanogel in the tumor microenvironment can be dynamically regulated, so that AuNR@PNIPAM-VAA nanogel produces switchable photoacoustic signals in the NIR-II window for tumor-specific enhanced photoacoustic imaging. In vitro results show that at pH 5.8, the absorption and photoacoustic signal amplitude of AuNR@PNIPAM-VAA nanogel in NIR-II increases up obviously after photothermal modulating, while they remain slightly change at pH 7.4. Quantitative calculation presents that photoacoustic signal amplitude of AuNR@PNIPAM-VAA nanogel at 1064 nm has ~ 1.6 folds enhancement as temperature increases from 37.5 °C to 45 °C in simulative tumor microenvironment. In vivo results show that the prepared AuNR@PNIPAM-VAA nanogel can achieve enhanced NIR-II photoacoustic imaging for selective tumor detection through dynamically responding to thermal field, which can be precisely controlled by external light.

Conclusions

This work will offer a viable strategy for the tumor-specific photoacoustic imaging using NIR light to regulate the thermal field and target the low pH tumor microenvironment, which is expected to realize accurate and dynamic monitoring of tumor diagnosis and treatment.
A low-calorie meal replacement improves body composition and metabolic parameters in shift workers with overweight and obesity: a randomized, controlled, parallel group trial
Authors: Sooriyaarachchi Piumika , Jayawardena Ranil , Pavey Toby , King Neil A.
Published: June 2024

Background

Shift work has been identified as a risk factor for several chronic health conditions including obesity. This study evaluated the impact of a low-calorie meal replacement (MR) as a dinner substitute on body composition and metabolic parameters in shift workers with overweight and obesity.

Methods

An 8-week parallel, randomized controlled trial was conducted on overweight and obese shift workers in a large hospital. An intervention group (IG) (n = 25) was provided with a low-calorie MR shake (∼200 kcal) as a replacement for dinner, every day for 8 weeks, while the control group (CG) (n = 25) continued their habitual diet. Anthropometric measurements, body composition, biochemical, and lifestyle data were assessed at the first and last visits. Analyses were done per protocol (PP) and by intention to treat (ITT).

Results

Over the study duration, both groups displayed moderate changes in anthropometric measurements and body composition, although these were not statistically significant according to the PP analysis. In the ITT analysis, apart from the hip circumference (HC), all other anthropometric parameters demonstrated significant group and time interactions, suggesting the advantageous effects of the meal replacement over the study period (P < 0.05). HDL and VLDL cholesterol measures showed significant main effects, influenced by both group (P = 0.031) and time (P = 0.050) respectively. The most pronounced dietary shift in the IG was a reduction in carbohydrate consumption and an increase in protein intake. Throughout the study, the meal replacement was well-tolerated, with no adverse events reported.

Conclusions

The meal replacement dietary intervention appears to offer beneficial health effects over time. Extended research is crucial to understand the broader implications of meal replacements across diverse populations.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000231741. Registered on 09 February 2022. https://www.anzctr.org.au/ACTRN12622000231741.aspx.
Exploration of new space elicits phosphorylation of GluA1(Ser831) and S6K and expression of Arc in the hippocampus in vivo as in long-term potentiation
Authors: Cagnetta Roberta , Lacaille Jean-Claude , Sonenberg Nahum
Published: June 2024

The brain responds to experience through modulation of synaptic transmission, that is synaptic plasticity. An increase in the strength of synaptic transmission is manifested as long-term potentiation (LTP), while a decrease in the strength of synaptic transmission is expressed as long-term depression (LTD). Most of the studies of synaptic plasticity have been carried out by induction via electrophysiological stimulation. It is largely unknown in which behavioural tasks such synaptic plasticity occurs. Moreover, some stimuli can induce both LTP and LTD, thus making it difficult to separately study the different forms of synaptic plasticity. Two studies have shown that an aversive memory task – inhibitory avoidance learning and contextual fear conditioning – physiologically and selectively induce LTP and an LTP-like molecular change, respectively, in the hippocampus in vivo. Here, we show that a non-aversive behavioural task – exploration of new space – physiologically and selectively elicits a biochemical change in the hippocampus that is a hallmark of LTP. Specifically, we found that exploration of new space induces an increase in the phosphorylation of GluA1(Ser831), without affecting the phosphorylation of GluA1(Ser845), which are biomarkers of early-LTP and not NMDAR-mediated LTD. We also show that exploration of new space engenders the phosphorylation of the translational regulator S6K and the expression of Arc, which are features of electrophysiologically-induced late-LTP in the hippocampus. Therefore, our results show that exploration of new space is a novel non-aversive behavioural paradigm that elicits molecular changes in vivo that are analogous to those occurring during early- and late-LTP, but not during NMDAR-mediated LTD.
Convergence of Fibonacci–Ishikawa iteration procedure for monotone asymptotically nonexpansive mappings
Authors: Alam Khairul Habib , Rohen Yumnam , Saleem Naeem , Aphane Maggie , Rzzaque Asima
Published: June 2024

In uniformly convex Banach spaces, we study within this research Fibonacci–Ishikawa iteration for monotone asymptotically nonexpansive mappings. In addition to demonstrating strong convergence, we establish weak convergence result of the Fibonacci–Ishikawa sequence that generalizes many results in the literature. If the norm of the space is monotone, our consequent result demonstrates the convergence type to the weak limit of the sequence of minimizing sequence of a function. One of our results characterizes a family of Banach spaces that meet the weak Opial condition. Finally, using our iterative procedure, we approximate the solution of the Caputo-type nonlinear fractional differential equation.
Chemical stimulation of geothermal reservoirs using retarded acid systems: current developments and potential directions
Authors: Grifka Jasmin , Licha Tobias , Heinze Thomas
Published: June 2024

Stimulation techniques to enhance fluid pathways are an important tool to make geothermal projects economically feasible. So far, hydraulic stimulation is used almost exclusively for reservoir-wide improvement of the permeability, but induced seismicity poses a challenge. Chemical stimulation on the other hand has been limited to the close vicinity of the borehole and has barely been considered for the creation of enhanced geothermal reservoirs. However, retardation mechanisms reducing the chemical reaction rate can be used to increase the radius of the chemical stimulation thus enabling a reservoir-wide enhancement of fluid pathways. In this work, we review the technologies of retardation mechanisms for chemical stimulation in geothermal systems and identify five groups of retardation techniques: (i) causing impaired mobility of the acid, e.g., by gelling agents; (ii) causing an impaired dissociation, e.g., by the in-situ generation of the reactive compounds; (iii) blocking the mineral surface area, e.g., by alternating injections of pad fluids and acids; (iv) reducing the reaction rate constant, e.g., by cooling; and (v) changing the chemical equilibrium through chelating agents. We found that most applications are currently based on the use of impaired dissociation, but present research focuses on the development and application of chelating agents. Most of these retardation techniques are adopted from the hydrocarbon industry, but there are several techniques that have not been applied in the geothermal context so far for various reasons. We identify a distinctive lack of in-depth descriptions of the retardation techniques in various studies—mostly to protect intellectual property. However, in the light of public concern regarding fracking techniques and to independently assess potential environmental hazards, scientific examination of proposed techniques is indispensable.
A comprehensive review of deep borehole heat exchangers (DBHEs): subsurface modelling studies and applications
Authors: Kolo Isa , Brown Christopher S. , Nibbs William , Cai Wanlong , Falcone Gioia , Nagel Thomas , Chen Chaofan
Published: June 2024

Deep borehole heat exchangers (DBHEs) with depths exceeding 500 m have been researched comprehensively in the literature, focusing on both applications and subsurface modelling. This review focuses on conventional (vertical) DBHEs and provides a critical literature survey to analyse (i) methodologies for modelling; (ii) results from heat extraction modelling; (iii) results from modelling deep borehole thermal energy storage; (iv) results from heating and cooling models; and (v) real case studies. Numerical models generally compare well to analytical models whilst maintaining more flexibility, but often with increased computational resources. Whilst in-situ geological parameters cannot be readily modified without resorting to well stimulation techniques (e.g. hydraulic or chemical stimulation), engineering system parameters (such as mass flow rate of the heat transfer fluid) can be optimised to increase thermal yield and overall system performance, and minimise pressure drops. In this active research area, gaps remain, such as limited detailed studies into the effects of geological heterogeneity on heat extraction. Other less studied areas include: DBHE arrays, boundary conditions and modes of operation. A small number of studies have been conducted to investigate the potential for deep borehole thermal energy storage (BTES) and an overview of storage efficiency metrics is provided herein to bring consistency to the reporting of thermal energy storage performance of such systems. The modifications required to accommodate cooling loads are also presented. Finally, the active field of DBHE research is generating a growing number of case studies, particularly in areas with low-cost drilling supply chains or abandoned hydrocarbon or geothermal wells suitable for repurposing. Existing and planned projects are thus presented for conventional (vertical) DBHEs. Despite growing interest in this area of research, further work is needed to explore DBHE systems for cooling and thermal energy storage.
Nail fold capillaroscopy as a potential tool to evaluate breast tumor
Authors: Kim Minsuk
Published: June 2024

It is necessary to verify whether nail fold capillaroscopy can be utilized for the early detection of breast cancer. To establish this technology, an animal model was developed, utilizing mice for nail fold observations. Nail fold capillaroscopy revealed a human-like anatomical pattern and facilitated the observation of cellular movement within blood vessels. Injection of MCF-7 or mammary fibroblasts in mice allowed the observation of cellular vibrations using motion microscopy from nail fold. We have named this technology ‘capillary cell motion microscopy.’ Intriguingly, we were able to identify distinct cellular vibrations in the MCF-7 group. Moreover, evaluating its effectiveness in mice with chemically induced cancer revealed higher sensitivity (81%-85%) compared to conventional methods (45%-68%). Capillary cell motion microscopy, operating at 0.5–1.5 Hz, provided clear distinction of tumor cells and demonstrated potential applicability in human subjects. While condition adjustments may be necessary, this method holds promise for noninvasive breast cancer detection through nail fold observations.
Detection of bladder tumor cells using motion features in urine
Authors: Kim Minsuk
Published: June 2024

Urinary exfoliated tumor cells have emerged as promising biomarkers for predicting, diagnosing, and guiding therapy in bladder cancer. Several methodologies based on biological and physical differences between normal cells and malignant tumor cells have been developed over the past few years. However, these methods still did not have sufficient sensitivity or specificity. In this study, a remote analysis protocol was devised utilizing motion microscopy. This technique amplifies vibrations within a recorded video by re-rendering motions, thereby generating highly magnified visuals. This approach aims to detect dynamic motions that may not be perceptible to the human eye under normal observation. Remarkably, motion microscopy unveiled discernible fluctuations surrounding bladder malignant tumor cells, which we referred to herein as cellular trail. The cellular trails were predominantly evident at around 1 Hz in amplified video images, with a velocity of 22 μm/s. Moreover, cellular trails were observed regardless of whether they were in a non-Newtonian or Newtonian fluid environment. Significantly, this phenomenon was distinguishable even in urine samples. In conclusion, we suggest motion microscopy as an innovative approach for detecting urinary malignant tumors with potential clinical utility as a complementary tool to cytology.
Evaluating a grant development public involvement funding scheme: a qualitative document analysis
Authors: Foster Alexis , Caunt Sharon , Schofield Holly , Glerum–Brooks Karen , Begum Samina , Gleeson Phil , Prestwich Graham , Baird Wendy
Published: June 2024

Background

Undertaking Patient and Public Involvement (PPI) when developing health and social care research grant applications is critical. However, researchers may not have any funding to undertake PPI when developing grants. In response, the National Institute for Health and Care Research- Research Design Service for Yorkshire and the Humber in the United Kingdom, provided Public Involvement Fund Awards of up to £600 to fund PPI activity when researchers were developing grant applications. Researchers provided post-activity reports about how they utilised the Public Involvement Fund. These reports were analysed with the aim of evaluating the usefulness of the Public Involvement Fund and to provide learning about supporting researchers to undertake PPI when developing grants.

Methods

The project was a qualitative document analysis of 55 reports. Initially a researcher coded four reports and three Public Contributors provided feedback. Researchers coded the remaining reports and identified key findings. A workshop was held with the three Public Contributors to develop the findings.

Results

Researchers accessing the Public Involvement Fund award were generally early career researchers or clinicians who did not have other sources of funding for pre-grant PPI input. Researchers felt the award was useful in enabling them to conduct PPI, which strengthened their grant applications. Some researchers found that the award limit of £600 and guidance encouraging expenditure within three months, made it difficult to undertake PPI throughout the full grant development process. Instead, the majority of researchers consulted Public Contributors on one or two occasions. Researchers struggled to recruit diverse members or run group sessions due to the time pressures of grant deadlines. Researchers wanted training on undertaking PPI alongside the financial support.

Conclusions

Researchers, especially early career researchers found having a Public Involvement Fund award instrumental in enabling them to undertake PPI when developing grant applications. It would be beneficial for similar schemes to be widely available. Schemes need to provide sufficient funding to enable meaningful PPI and allow researchers to hold the award for long enough to facilitate involvement during the whole grant development process. Researchers continue to need training on undertaking PPI.
Influence of protective clothing and masks on facial trustworthiness in an investment game: insights from a Chinese population study
Authors: Wang Weiping , Li Zhifan , Lin Xin , Sun Yu-Hao P. , Wang Zhe , Wang Yong
Published: June 2024

Facial features are important sources of information about perceived trustworthiness. Masks and protective clothing diminish the visibility of facial cues by either partially concealing the mouth and nose or covering the entire face. During the pandemic, the use of personal protective equipment affected and redefined who trusts whom in society. This study used the classical investment game of interpersonal trust with Chinese participants to explore the impact of occlusion on interpersonal trust. Faces with moderate initial trustworthiness were occluded by a mask or protective clothing in Experiment 1 and were digitally occluded by a square in Experiment 2, and faces with three levels of initial trustworthiness were occluded by a mask in Experiment 3. Results showed that both undergraduates (Experiment 1a) and non-student adults (Experiment 1b) perceived the faces with protective clothing as more trustworthy than faces wearing standard masks and faces not wearing masks. Faces with the top halves showing were perceived as trustworthy as full faces, while faces with the bottom halves showing were perceived as less trustworthy. The effect of masks is weak and complex. Masks reduced participants’ trust in faces with high initial trustworthiness, had no effect on faces with low and moderate initial trustworthiness, and only slightly increased the trust of undergraduates in faces with moderate initial trustworthiness. Our findings indicate that the lack of information caused by occlusion and the social significance associated with occlusion collectively affect people’s trust behavior in Chinese society. We believe the findings of this study will be useful in elucidating the effects of personal protective equipment usage on perceptions of trustworthiness.
Characterization and screening of cotton (Gossypium hirsutum L.) germplasm for leafhopper (Amrasca biguttula biguttula (Ishida)) resistance
Authors: Mawblei Chossterfield , Premalatha Nallathambi , Manivannan Alagarsamy , Senguttuvan Kannan
Published: June 2024

Background

Cotton (Gossypium hirsutum L.) is one of the most significant fibre and cash crops and plays an important role in Indian industrial and agricultural economies. However, over the years quantity and quality have been hampered by the pest leafhopper. Leafhopper alone has been shown to cause yield losses of up to 40%. In this study, screening and evaluation were performed to identify and categorize 100 cotton genotypes along with 5 checks as resistant, moderately resistant, sensitive and highly sensitive to leafhoppers.

Results

A total of hundred genotypes were evaluated along with five checks for leafhopper resistance. Based on the screening results, a total of 19 genotypes were resistant to leafhoppers, which was on par with the findings of the check KC 3. The contents of total soluble sugar, total soluble protein, and total free amino acids were significantly positively correlated with the mean grade, whereas total phenols content and trichome density were significantly negatively correlated with the susceptibility grade. However, based on screening and biochemical analysis, the genotypes KC 2, JR-23, Samaru-26-T, D 4, TCH 1728, RS 253, and B-61-1862 exhibited high resistance to leafhopper.

Conclusion

According to the findings of this study, choosing genotypes with high total phenolics content together with high trichome density and low contents of total soluble sugar, total soluble protein, and free amino acids may aid in the development of resistant genotypes.
Extraction and evaluation of cable forces of a cable-stayed bridge based on amplitude and phase estimation method
Authors: Wang Weiguo , Song Xiaodong , Yu Yang , Chang Hongchen , Yu Wenxin , Xiong Wen
Published: June 2024

In order to identify the time-varying frequency and amplitude of structural vibration based on the bridge structural health monitoring data and obtain the cable force of cable-stayed bridges in real time, a spectrum analysis method based on amplitude and phase estimation (APES) was proposed in this study. The amplitude spectrum of the acceleration data is first calculated by the APES method, the real-time spectrogram of the cable is obtained by the sliding window method. Then the modal frequency and amplitude are automatically extracted from the real-time spectrum by using a frequency extrusion post-processing technique, which can be regarded as the average value of the instantaneous frequency and amplitude respectively. Next, the fundamental frequency of the cable is extracted by using an automatic identification method, and the performance of the proposed method is verified. Finally, real-time scoring of cable forces and structural condition assessment is achieved with consideration of the moderation index model as well as the material strength. The results show that the APES method can use shorter calculation samples than the traditional Fast Fourier Transform (FFT) to obtain higher resolution and more accurate amplitude, which provides a theoretical basis for the real-time identification of fundamental frequency based on short-term monitoring data. The frequency extrusion post-processing-algorithm can reduce the spectrum recognition delay and improve timeliness of the cable force evaluation. The time-varying cable force with an interval of 10 s can be used to reflect the health status of the cable in time. The research results can provide technical support for the real-time extraction of cable force of long-span cable-stayed bridges, and can also provide an effective basis for component condition evaluation and bridge maintenance decision-making.
Amplifying the Patient's Voice in Oncology Early-Phase Clinical Trials: Solutions to Burdens and Barriers
Authors: Spencer Kristen , Butenschoen Henry , Alger Emily , Bachini Melinda , Cook Natalie
Published: June 2024

Dose-finding oncology trials (DFOTs) provide early access to novel compounds of potential therapeutic benefit in addition to providing critical safety and dosing information. While access to trials for which a patient is eligible remains the largest barrier to enrollment on clinical trials, additional direct and indirect barriers unique to enrollment on DFOTs are often overlooked but worthy of consideration. Direct barriers including financial costs of care, travel and time investments, and logical challenges including correlative study designs are important to bear in mind when developing strategies to facilitate the patient experience on DFOTs. Indirect barriers such as strict eligibility criteria, washout periods, and concomitant medication restrictions should be accounted for during DFOT design to maintain the fidelity of the trial without being overly exclusionary. Involving patients and advocates and incorporating patient-reported outcomes (PROs) throughout the process, from initial DFOT design, through patient recruitment and participation, is critical to informing strategies to minimize identified barriers to offer the benefit of DFOTs to all patients.
Intra-treatment hypoxia directed major radiation de-escalation as definitive treatment for human papillomavirus-related oropharyngeal cancer.
Authors: LEE NANCY Y. , Sherman Eric Jeffrey , Schöder Heiko , Wray Rick , White Charlie , Dunn Lara , Hung Tony , Pfister David G. , Ho Alan Loh , McBride Sean Matthew , Yu Yao , Zakeri Kaveh , Kalman Noah , Rutter Charles , Morris Luc , Singh Bhuvanesh , Boyle Jay , Ganly Ian , Wong Richard J. , Riaz Nadeem
Published: June 2024

6007

Background: We previously reported that surgery to the primary site with hypoxia-directed de-escalated radiation to the neck for human papillomavirus associated oropharyngeal carcinoma (HPV+ OPC) can lead to excellent oncologic outcomes. We now report the results of a successor multi-center phase II trial of hypoxia-directed de-escalated chemoradiotherapy without surgery for HPV+OPC. Methods: HPV+ OPC (T0-2/N1-N2c/AJCC 7th) patients were eligible for enrollment. Tumors without evidence of hypoxia on 18F-FMISO (fluoromisonidazole) PET received de-escalated chemoradiation to 30Gy while those with hypoxia received chemoradiation to 70Gy. The primary objective was achieving a 2-year locoregional control (LRC) of 95% (failure was locoregional recurrence where surgical salvage was unfeasible) with a 7% non-inferiority margin. We enrolled a total of 158 subjects upfront to account for a 5% loss due to death (of reasons other than cancer) or follow-up. Secondary objectives were local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS), toxicities, and patient-reported MD Anderson Dysphagia Inventory (MDADI) scores. LF, RF, and DM were estimated using the Cumulative Incidence Function, and OS was estimated using the Kaplan-Meier method. Results were reported up to 1/31/2024. Results: From 4/28/20-4/17/23, 158 HPV+ OPC patients were enrolled where150 patients were eligible for analyses. Patient characteristics: Tonsil (43%); Base of Tongue (47%); unknown primary (10%); >/=10 pack years (22%); T0 (9%), T1 (44%), T2 (47%); N1 (14%), N2a (11%), N2b (59%), N2c (16%). 111 (74%) received 30Gy; 95% cisplatin. With 24 months (8-43) of median follow-up, the 2-year LF, RF, DM rates were 4.2%, 6.9%, 2.0%, respectively. The 2-year overall survival probability was 99%. Only 2 patients could not undergo salvage surgery [one 30Gy (second recurrence); one 70Gy (M1)], both received systemic therapy with durable response. Acute grade 3-4 toxicities were 32% (67% neutropenia). Mean MDADI scores: 92.93 (baseline); 68.24 (3 weeks), 91.45 (4 months) after chemoradiation. Conclusions: These early data indicate that major de-escalation to 30Gy based on hypoxia status achieved significant toxicity reduction without compromise in survival for HPV+ OPC treated with chemoradiation without surgery. Clinical trial information: NCT03323463 .
A phase II trial of neoadjuvant docetaxel/5-FU/cisplatin in combination with prophylactic pegteograstim in unresectable, locally advanced nasal cavity/paranasal squamous cell carcinoma: KCSG HN18-07.
Authors: An Hojung , Keam Bhumsuk , Shin Seong Hoon , Kim Min Kyoung , Kim Sung-Bae
Published: June 2024

6020

Background: Squamous cell carcinoma (SCC) arising from paranasal sinus and nasal cavity (PNSNC) is often diagnosed at locally advanced stage. Neoadjuvant strategies have been explored to improve prognosis and facilitate organ preservation. The efficacy of triplet neoadjuvant chemotherapy (NAC) has not been established prospectively. We conducted a phase II trial of neoadjuvant docetaxel/5-FU/cisplatin (DFP) combined with prophylactic pegteograstim in unresectable, locally advanced PNSNC (KCT0003377). Methods: Eligible patients had unresectable SCC of PNSNC, were aged 19-75, had an ECOG performance status of 0/1, and demonstrated adequate organ function. Patients with distant metastasis were excluded. Criteria for unresectability included tumor or lymph node fixation, clinical T3/4 stage, or potential compromise of critical organ function (e.g., necessitating eyeball exenteration). NAC comprised three cycles of docetaxel (75mg/m2 on Day 1), cisplatin (75mg/m2 on Day 1, 60mg/m2 for those aged ≥65), and 5-FU (1,000mg/m2 on Days 1-4) administered every 3 weeks. Prophylactic pegteograstim (6mg) was administered on Day 6 or 7. The primary outcome was the overall response rate (ORR), with secondary outcomes including progression-free survival (PFS), the eyeball preservation rate at 24 months, and safety. The study required 28 patients to achieve a power of 80% (P0=0.45, P1=0.70, α-error=0.05, 10% dropout rate). Results: Between 2019 and 2023, 28 patients were screened, and 27 received at least one cycle of NAC. The median age was 58 years (range: 41-71), with 24 males. Seventeen had maxillary sinus origin, and ten had nasal cavity origin. Twenty-two patients had T4 disease, and six had N2 disease. The ORR was 64.3% (5 complete responses, 13 partial responses). Post-NAC treatments included surgery alone (n=2), concurrent chemoradiotherapy (CCRT) (n=15), surgery followed by CCRT (n=2), or radiotherapy (RT) (n=5). Procedures performed were total maxillectomy (n=4), partial maxillectomy (n=3), and endoscopic sinus surgery (n=2). With a median follow-up of 21.5 months (range: 0.1-53.0), the 2-year PFS and eyeball preservation rate were 64% and 100%, respectively. Fourteen patients experienced Grade ≥3 adverse events (AEs): hematologic (46.4%), non-hematologic (14.3%), with Grade 3/4 neutropenia (32.1%) and febrile neutropenia (14.3%). Dose reduction or delay occurred in 9 patients (33.3%). One patient died on Day 6 of cycle 1. Conclusions: DFP NAC demonstrated promising efficacy and an excellent eyeball preservation rate with manageable toxicity. DFP NAC with prophylactic pegteograstim, could be a reasonable option for patients with locally advanced SCC of the PNSNC. Follow-up is ongoing. Clinical trial information: KCT0003377 .
Molecular analysis of surgical margins with NGS to assess microscopic residual disease in early oral squamous cell carcinomas.
Authors: Moya-Plana Antoine , Vasseur Damien , Auperin Anne , Dayris Thibault , Lacroix Ludovic , Temam Stephane
Published: June 2024

6063

Background: The prognosis of early oral squamous cell carcinomas (OSCC) is strongly correlated with local disease control. However, patients with T1-T2 OSCC operated with clear margins have a 5-year local relapse rate of 10 to 15%. An accurate evaluation of the microscopic residual disease (MRD) is therefore essential. Interestingly, innovative techniques have recently been developed to detect circulating tumor DNA. Methods: A prospective multicenter trial based on patients with T1-T2 OSCC treated surgically with clear margins, was designed to assess the feasibility of a molecular analysis (tetranucleotide instability) of these margins to evaluate a potential MRD while adapting the postoperative strategy (NCT00232960). We, then, evaluate the feasibility of detecting MRD in the margins by identifying specific molecular abnormalities in the primary tumor with Whole Exome Sequencing (WES) and explore them in margins with deep target NGS panel (TGS) and digital PCR (dPCR) for hotspot mutations. Results: 310 patients were included initially with 216 tumor/margins samples available for molecular analysis. After a standard pathologic analysis, all surgical margins were negative.Median follow-up was 58 months [30;83]. Tumor was informative for tetranucleotide instability analysis in 63% of cases. Positive molecular margins were observed in 17.3% of cases, leading to a postoperative treatment (surgery or radiotherapy). In informative tumors, molecularly driven treatment seemed to lower the 5-year local recurrence rate from 14.1% to 6.4% (p=0.15). Among this initial cohort, 108 primary tumors were secondarily screened by WES to find mutations of interest, with an informativity rate of 75%. Positive molecular results (TGS or dPCR), with at least one positive margin, were observed in 19.4% of patients. Then, analyzing retrospectively the oncologic outcomes, we observed a significant benefit for local control at 5 years for patients with TGS-dPCR negative results in all margins compared to pathologic negative margins (91.7% versus 64.1%, p=0.02). Conclusions: To our knowledge, this is the first report of local MRD assessment after surgery using NGS.Molecular analysis of resection margins for early OSCC lead to a better evaluation of MRD and personalized postoperative decision making to improve local control. Clinical trial information: NCT00232960 .