bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the prediction of patient survival with the aid of residual convolutional neural network (ResNet) in colorectal cancer with unresectable liver metastases treated with bevacizumab-based chemotherapy
Authors: Chiu Sung-Hua , Li Hsiao-Chi , Chang Wei-Chou , Wu Chao-Cheng , Lin Hsuan-Hwai , Lo Cheng-Hsiang , Chang Ping-Ying
Published: December 2024

Background

To verify overall survival predictions made with residual convolutional neural network-determined morphological response (ResNet-MR) in patients with unresectable synchronous liver-only metastatic colorectal cancer (mCRC) treated with bevacizumab-based chemotherapy (BBC).

Methods

A retrospective review of liver-only mCRC patients treated with BBC from December 2011 to Apr 2021 was performed. Patients who had metachronous liver metastases or received locoregional treatment before the initiation of BBC were excluded. The percentage of downstaging to curative treatment and overall survival (OS) were recorded. Two abdominal radiologists evaluated portal venous phase CT images based on the morphological criteria and divided the images into Groups 1, 2, and 3. These images were used to establish the radiologists-determined morphological response (RD-MR), which classified patients into responders and non-responders based on the morphological change 3 months after the initiation of BBC. Then, the Group 1 and 3 images classified by the radiologists were input into ResNet as the training dataset. The trained ResNet then redivided the Group 2 images into Groups 1, 2 and 3. The ResNet-MR was determined on the basis of these redivided images and the initial Group 1 and 3 images classified by the radiologists.

Results

Eighty-four patients were included in this study (53 males and 31 females, with a median age of 60.0 years). The follow-up time ranged from 10 to 86 months. A total of 407 CT images were input into ResNet as the training dataset. Both RD-MR and ResNet-MR correlated with OS (p value = 0.0167 and 0.0225, respectively). Regarding discriminatory ability for mortality, ResNet-MR had higher area under curve than RD-MR at both 1 year and 2 years and showed a significant difference in discriminatory ability (p-value = 0.0321) at 2 years. RD-MR classified 28 patients (33.3%) as responders, and ResNet-MR classified an additional 16 patients (19.0%) as responders; these 16 patients had longer OS than the remaining non-responders in the RD-MR group (27.49 versus 21.20 months, p value = 0.043) and had a higher percentage of downstaging (37.5% versus 17.5%, p value = 0.1610).

Conclusions

In CRC patients with liver metastases treated with BBC, prediction of survival can be improved with the aid of ResNet, enabling optimized individualized treatment.
Development and validation of intravoxel incoherent motion diffusion weighted imaging-based model for preoperative distinguishing nuclear grade and survival of clear cell renal cell carcinoma complicated with venous tumor thrombus
Authors: Zhao Jian , Xu Honghao , Fu Yonggui , Ding Xiaohui , Wang Meifeng , Peng Cheng , Kang Huanhuan , Guo Huiping , Bai Xu , Zhou Shaopeng , Liu Kan , Li Lin , Zhang Xu , Ma Xin , Wang Xinjiang , Wang Haiyi
Published: December 2024

Objective

To assess the utility of multiparametric MRI and clinical indicators in distinguishing nuclear grade and survival of clear cell renal cell carcinoma (ccRCC) complicated with venous tumor thrombus (VTT).

Materials and methods

This study included 105 and 27 patients in the training and test sets, respectively. Preoperative MRI, including intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), was performed. Renal lesions were evaluated for IVIM-DWI metrics and conventional MRI features. All the patients had postoperative histologically proven ccRCC and VTT. An expert uropathologist reviewed all specimens to confirm the nuclear grade of the World Health Organization/ International Society of Urological Pathology (WHO/ISUP) of the tumor. Univariate and multivariable logistic regression analyses were used to select the preoperative imaging features and clinical indicators. The predictive ability of the logistic regression model was assessed using receiver operating characteristic (ROC) analysis. Survival curves were plotted using the Kaplan–Meier method.

Results

High WHO/ISUP nuclear grade was confirmed in 69 of 105 patients (65.7%) in the training set and 19 of 27 patients (70.4%) in the test set, respectively (P = 0.647). Dp_ROI_Low, tumor size, serum albumin, platelet count, and lymphocyte count were independently related to high WHO/ISUP nuclear grade in the training set. The model identified high WHO/ISUP nuclear grade well, with an AUC of 0.817 (95% confidence interval [CI]: 0.735–0.899), a sensitivity of 70.0%, and a specificity of 77.8% in the training set. In the independent test set, the model demonstrated an AUC of 0.766 (95% CI, 0.567–0.966), a sensitivity of 79.0%, and a specificity of 75.0%. Kaplan–Meier analysis showed that the predicted high WHO/ISUP nuclear grade group had poorer progression-free survival than the low WHO/ISUP nuclear grade group in both the training and test sets (P = 0.001 and P = 0.021).

Conclusions

IVIM-DWI-derived parameters and clinical indicators can be used to differentiate nuclear grades and predict progression-free survival of ccRCC and VTT.
Minimally invasive balloon-assisted sinus floor elevation vs. conventional transcrestal procedure in terms of new bone formation in a split-mouth Goettingen minipig model
Authors: Kolk Andreas , Bauer Florian , Weitz Jochen , Stigler Robert , Walch Benjamin , Grill Florian , Boskov Marko
Published: December 2024

Purpose

Currently, maxillary sinus floor (SF) elevation is based on off-the-shelf allogeneic, xenogeneic or synthetic bone augmentation materials (BAM) that are implanted via an open lateral sinus wall approach (OSFE). However, this invasive method is associated with postoperative complications caused by an inadequate blood supply of the alveolar ridge. Balloon-assisted procedures are minimal invasive alternatives with lower complication rates. The aim was to evaluate local new bone (NB) formation in the SF following the application of a particulate BAM (Easy graft) via two different SF elevation techniques in a split mouth mini-pig sinus augmentation model.

Material and methods

Seven adult Goettingen minipigs were used for evaluation of a biphasic ceramic (PLGA/ß-TCP) BAM in the elevated SF region. Treatments were randomized to the contralateral sinus sites and included two procedures: OSFE (control group) versus minimally invasive SF elevation by a balloon-lift-control system (BLC) (treatment group). The animals were euthanized after 28 and 56 days for analysis of new bone (NB) formation.

Results

The biphasic synthetic BAM implanted via BLC increased more NB formation (5.2 ± 1.9 mm and 4.9 ± 1.6 mm vs. 2.6 ± 0.5 mm) and osseointegration of the particles (18.0 ± 6.0% and 25.1 ± 18.2% vs. 10.1 ± 8.0%, p < 0.05) compared to the control.

Conclusions

Implantation of a biphasic synthetic BAM enhanced NB formation in the mini-pig maxillary sinus at both time points and in both groups, although BLC resulted in a slightly better total NB formation compared to the control.

Graphical abstract
“Do good and talk about it”: informal representation and migrant-led civil society organizations’ mediation between low-wage labor migrants and state institutions in the GCC countries
Authors: Burmeister-Rudolph Mira
Published: December 2024

Low-wage labor migrants experience major human and working rights abuses in the Gulf Cooperation Council countries despite national labor laws and signatures to various human rights conventions. On paper, India has established an institutional framework of transnational social protection for its officially estimated 5.5 million low-wage workers migrating to the Gulf Cooperation Council countries, e.g., financial emergency support, repatriation services, and walk-in centers. However, migrants in low-wage employment often cannot access substantive social rights in practice. Indian upper/middle-class migrant civil society groups mediate their access to Indian embassies’ services and the destination countries’ state institutions. The realization of social rights via informal, third-party representation stems from a representational disjuncture between low-wage labor migrants and the Indian state, which is rooted in their historical socioeconomic marginalization, limitations of the formal political system, and the constitutive role of informality in shaping and structuring citizen-state interactions in India. Through the lens of Piper and von Lieres’ (2015) concept of mediated citizenship and based on data from semi-structured interviews and participant observation of migrant support networks in the Gulf countries, this article examines why mediation takes place and how volunteers speak and take action for marginalized migrants in low-wage employment and consequences of mediation. It argues that migrant volunteer organizations and individuals are powerful stakeholders in the migration governance in the GCC region, as they possess leverage over who has (better) access to state institutions and the provision of social and human rights. Their status as intermediaries underlines the disaggregation of Indian citizenship along class and caste lines, which can be (mis)-used by mediators to pursue their interests, resulting in ambiguous effects. The article contributes to perspectives on migration governance in the GCC region, transnational social policies, and migrant volunteering.
Long-term evaluation of Elmelegy’s technique of local muscle transposition for the functional restoration of large upper or lower lip defects
Authors: Elmelegy Nader G.
Published: December 2024

Background

Although more than 200 techniques have been reported for the reconstruction of the upper and lower lip defects since 1000 BC, none of them is ideal.

Local flaps may result in extra skin incisions and in some cases, the surgeon may be confronted with the lack of sufficient tissues for the reconstruction of large defects.

Several techniques have been described for near-total lip reconstruction. The two major available techniques are local flap reconstruction (Bernard–von Burrow–Webster technique) and free micro-vascular tissue transfer.

In this study, we are going to evaluate the functional results of using local muscles transposition-assisted dermal fat flap and muco-buccal flap in the treatment of large upper or lower lip defects.

Materials and methods

This study was carried out on 128 patients, who presented to us with malignant tumors affecting the lips.

Results

Lip defect sizes ranged from 4 to 6 cm in diameter. No flap failure was seen and desirable function and accepted esthetic results were obtained. The flap survival was 100%, and healing was eventful in all cases. No cases of microstomia were reported.

Conclusion

The use of local muscle transposition-assisted dermal fat flap and muco-buccal flap technique, showed excellent results in regaining oral competence and lip mobility, and as much as possible, increased the aesthetic outcome.

Level of evidence

IV therapeutic study.
The relationship of macular vessel density and foveal avascular zone with pulse wave velocity and central blood pressure in healthy adults: Persian cohort study
Authors: Heidarzadeh Hamid Reza , Ebrahimi Miandehi Elaheh , Shoeibi Nasser , Ansari Astaneh Mohammad Reza , Hosseini Seyedeh Maryam , Abrishami Majid , Motamed Shariati Mehrdad , Eslami Saeid , Arjmand Parnian , Abrishami Mojtaba
Published: December 2024

Background

To evaluate the correlation of macular vessel density (VD) and foveal avascular zone (FAZ) parameters measured on optical coherence tomography angiography (OCTA) with systemic arterial stiffness using pulse wave velocity (PWV), pulse wave analysis, arterial age, and central blood pressure (CBP) measurements in healthy subjects.

Methods

In a comparative, cross-sectional, observational study, healthy adults who participated in the PERSIAN Cohort study at Mashhad University of Medical Sciences were included in this study. The study involved using a spectral domain OCTA device to obtain 3 × 3 and 6 × 6 mm scans of the macular superficial capillary plexus (SCP) VD, deep capillary plexus (DCP) VD, and FAZ vascular analysis. Additionally, we used the SphygmoCor XCEL System (AtCor, Itasca, IL) to analyze systemic vascular parameters like CBP and PWV.

Results

The study included 296 healthy participants with a mean age of 39.2 ± 6.7 years, and 152 subjects (51.3%) were female. Female participants were found to have higher DCP VD and FAZ area values. Age showed a negative correlation with SCP and DCP VDs. PWV showed a negative correlation with parafoveal DCP VDs, but no correlation was observed between macular VDs and aortic diastolic and systolic pressures.

Conclusion

In conclusion, age was found to have a negative impact on macular SCP and DCP VDs. In addition, higher arterial stiffness was found to correlate with a lower parafoveal DCP VD value. These findings suggest macular OCTA parameters may be used as early markers of systemic arterial disease.
Retinal microvascular changes in systemic lupus erythematosus assessed by optical coherence tomography angiography
Authors: Ferreira André , Viveiros Luísa , Faria Raquel , Bragança Francisca , Abreu Ana Carolina , Santos Daniela , Furtado Maria João , Lume Miguel , Menéres Pedro , Andrade José P.
Published: December 2024

Purpose

To assess the retinal microvasculature of Systemic Lupus Erythematosus (SLE) patients using Optical Coherence Tomography Angiography (OCTA).

Methods

Twenty adult SLE patients without disease activity and no ocular manifestations were recruited and cross-sectionally assessed. A demographically similar cohort of healthy subjects was used for comparison. The main outcome is vascular density (VD). As secondary outcomes, foveal avascular zone (FAZ) parameters, total vessel length (TVL), vessel length density (VLD), vessel diameter and tortuosity, branchpoint density (BD) and fractal dimension (FD) were evaluated.

Results

Forty eyes of 40 women (20 SLE patients and 20 healthy subjects) were enrolled with a mean ± SD age of 36.7 ± 9.9 years. In both the superficial and deep capillary plexuses, SLE patients presented significantly lower VD and TVL values, mean vessel diameter and FD (all p < 0.005). No significant differences were found in FAZ values. A negative correlation was found between age and FAZ parameters and between age and TVL, VLD and FD in the superficial capillary plexus (all p < 0.05).

Conclusions

This study supports the evidence of subclinical retinal microvascular changes in adult SLE patients, providing a more comprehensive characterization of vascular changes. We found vessel diameter and length and FD are decreased in SLE.

Trial registration

NCT05863689, 2023-10-19.
Barriers and facilitators of school-based obesity prevention interventions: a qualitative study from the perspectives of primary school headteachers
Authors: Saleh Mohamed , Ba-Break Maryam , Abahussin Asma
Published: December 2024

Background

Childhood obesity is a growing global health issue. The World Health Organization identifies obesity as a significant risk factor for Non-Communicable Diseases and considers it a pandemic. This study aimed to investigate headteachers' perspectives and practices concerning childhood obesity prevention interventions in primary schools highlighting the barriers and facilitators for those interventions.

Methods

This qualitative study used a phenomenological approach and semi-structured interviews with headteachers of primary schools in the West Yorkshire area, UK. The collected data was transcribed and analysed using inductive thematic analysis.

Results

A total of 32 interviews with headteachers were conducted. The data indicated that interventions meant to prevent childhood obesity in schools are influenced by a range of barriers and facilitators that are organized under the following seven key themes: (1) staff perception of obesity prevention at school; (2) school policies on eating at schools; (3) School curriculum on healthy diets and physical activities; (4) role models at school; (5) partnership with parents; (6) extra-curricular activities on healthy diets and physical activities; (7) School capacity and resources.

Conclusions

Childhood obesity prevention interventions vary across UK schools depending on staff and head teachers' beliefs, awareness, commitments, school resources, parents' involvement and parents’ awareness, income, and culture. The study suggests raising awareness of childhood obesity among parents and staff, involving external partners like school nurses for training, making all primary pupils eligible for free meals, and providing schools with guidance on securing government funding. It provides a foundation for improving school-based strategies that indirectly contribute to better health outcomes for children.
Virtual reality simulation for facilitating critical reflection and transformative learning: pedagogical, practical, and ethical considerations
Authors: Soilis Niki , Bhanji Farhan , Kinsella Elizabeth Anne
Published: December 2024

There is growing recognition that preparing health professionals to work with complex social issues in the delivery of healthcare requires distinct theoretical and pedagogical approaches. Recent literature highlights the significance of employing simulated environments which aim to immerse learners in the experiences of diverse populations and bridge the gap between academic learning and lived realities across a diverse society. Virtual Reality (VR) is gaining traction as a promising pedagogical approach in this context. VR has been argued to offer distinct advantages over traditional educational methods by allowing learners to see the world through the eyes of diverse populations, and to learn about social injustices while immersed in a mediated environment. It also has practical benefits in its capacity to expose large number of students to these topics with relatively modest resources compared to other approaches. This debate article explores VR as an innovative pedagogical approach for facilitating critical reflection, dialogue and transformative learning about social issues in health professions education (HPE). It examines the potential affordances as well as risks and dangers of integrating VR into educational programs and highlights key pedagogical, practical, and ethical considerations. Emphasis is placed on the importance of these considerations in efforts toward ethical, safe, and respectful use of VR in educational settings. This paper contributes to the ongoing dialogue on VR simulation as an innovative approach to HPE and highlights the importance of creating conditions that maximize its educational benefits and minimize potential harms.
PEARLS debriefing for social justice and equity: integrating health advocacy in simulation-based education
Authors: Soilis Niki , Kinsella Elizabeth Anne , Eppich Walter , Cheng Adam , Beavers Lindsay , Bhanji Farhan
Published: December 2024

Addressing health inequities in health professions education is essential for preparing healthcare workers to meet the demands of diverse communities. While simulation has become a widely recognized and effective method for providing safe and authentic clinical learning experiences, there has been limited attention towards the power of simulation in preparing health practitioners to work with groups who experience health disparities due to systems of inequality. Balancing technical proficiency with educational approaches that foster critical reflection and inform action oriented towards social accountability is essential. Transformational learning promotes the development of critical consciousness through critical reflection. Debriefing plays a crucial role in fostering learning in this direction by providing a structured opportunity to critically reflect on taken for granted assumptions, examine power and privilege embedded within systems and structures, and empower learners to take action toward changing those conditions. Building on the Promoting Excellence and Reflective Learning in Simulation (PEARLS) Healthcare Debriefing Tool, we propose a PEARLS Debriefing for Social Justice and Equity (DSJE) Tool that specifically directs attention to systems of inequality that contribute to health disparities for vulnerable groups across a range of simulation scenarios. This approach has two aims: (a) to transform debriefings into a critically reflective space by engaging learners in dialogue about social and structural determinants of health that may create or perpetuate inequities and (b) to foster critical reflection on what actions can be taken to improve the health and well-being of identified at risk and vulnerable groups. From this perspective, we can use the adapted PEARLS Tool to incorporate conversations about systems of inequality, equity, diversity, and inclusion (EDI) into our existing educational practices, and make concentrated efforts towards community-driven and socially conscious simulation-based education (SBE).
First preclinical SPECT/CT imaging and biodistribution of [165Er]ErCl3 and [165Er]Er-PSMA-617
Authors: Saeedi Saghez Behrad , Rodríguez-Rodríguez Cristina , Esquinas Pedro Luis , Merkens Helen , Bénard François , Radchenko Valery , Yang Hua
Published: December 2024

Background

165Er (t1/2 = 10.4 h, Ex-ray = 47.1 keV (59.4%) and 54.3 keV (14.3%)) is a promising radionuclide suitable for targeted Auger electron therapy of cancer. 165Er can be produced at a relatively low cost, high yield, and high purity using small medical cyclotrons. As a late lanthanide, 165Er is easy to label and can be used as a surrogate for other lanthanides or Ac in proof-of-concept studies. In this report, we explore the radiochemistry, in vitro, and in vivo behavior of [165Er]ErCl3 and [165Er]Er-PSMA-617 to showcase the application of this radionuclide. Particularly, we report the first phantom and preclinical SPECT imaging of this radionuclide leveraging its characteristic X-ray photon emissions.

Results

The 165Ho(p,n)165Er nuclear reaction using a 13 MeV cyclotron demonstrated production yields of up to 25 ± 5 MBq. µA−1 h−1 at the end of the bombardment. After the purification (4.0 ± 0.5 h) using a sequential combination of cation exchange and extraction chromatography, 4-h irradiation produced up to 1.5 GBq of [165Er]ErCl3. High molar activity [165Er]Er-PSMA-617 was prepared (~ 200 MBq/nmol). [165Er]Er-PSMA-617 showed a LogD7.4 value of -2.34 ± 0.24 meaning high hydrophilicity of the complex as expected. The stability of [165Er]Er-PSMA-617 in saline, human, and mouse serum was studied and showed intact tracer after 12 h in all three cases. [165Er]ErCl3 and [165Er]Er-PSMA-617 were both taken up by LNCaP cells. PSMA-617 has IC50 at nanomolar range for [165Er]Er-PSMA-617 in LNCaP cells. SPECT images with preclinical phantoms showed good uniformity, spatial resolution, and quantitative accuracy. SPECT/CT imaging in LNCaP tumor-bearing mice injected with [165Er]Er-PSMA-617 showed high tumor uptake and quantitative accuracy when comparing the results to ex vivo biodistribution %IA/g values. Mice injected with [165Er]ErCl3 showed uptake in bone structures and excretion through both liver and kidneys.

Conclusions

This study demonstrated the preclinical use of 165Er for the first time. Using [165Er]ErCl3 and [165Er]Er-PSMA-617 as examples, the radiochemistry, cell, and animal studies showed that 165Er can be used as a tool for evaluating targeted radiopharmaceuticals. The X-ray emission from 165Er can be used for quantitative SPECT imaging in mice.
[89Zr]Zr-DFO-TOC: a novel radiopharmaceutical for PET imaging of somatostatin receptor positive neuroendocrine tumors
Authors: Sanwick Alexis M. , Haugh Katherine N. , Williams Evan J. , Perry Kala A. , Thiele Nikki A. , Chaple Ivis F.
Published: December 2024

Background

Neuroendocrine tumors (NETs) are clinically diverse types of tumors that can arise anywhere in the body. Previous studies have shown that somatostatin receptors (SSTRs) are overexpressed on NET cell membranes relative to healthy tissue, allowing for tumor targeting through radiolabeled somatostatin analogs (SSAs). This work aims to develop a novel 89Zr-labeled tracer incorporating the SSA, octreotide (TOC), for positron emission tomography (PET) imaging of SSTR + NETs and predictive dosimetry calculations, leveraging the excellent nuclear (t½ = 3.27 days, β+ = 22.3%, β+avg = 395.5 keV) and chemical characteristics (+ 4 oxidation state, preferential coordination number of 7/8, favorable aqueous chemistry) of 89Zr. In combination with 89Zr, the known radiochemistry with the chelator deferoxamine (DFO) gives reason to believe that this radiopharmaceutical incorporating an octreotide conjugate will be successful in studying the suitability of detecting SSTR + NETs.

Results

Radiochemical tracer assessment indicated that amounts as low as 0.1 nmol DFO-TOC can be effectively radiolabeled with 89Zr, while maintaining ≥ 95% radiochemical yield. The stability of the compound was found to maintain radiochemical yields of 89.6% and 88.7% on the benchtop and in mouse serum, respectively, after 9 days. Receptor binding and competitive receptor blocking assays compared AR42J (high SSTR expression), PC-3 (moderate SSTR expression), and PANC-1 (minimal SSTR expression) cell lines at time points up to 6 days. In vitro studies demonstrated highest uptake in AR42J cells, and statistically significant differences in tracer uptake were seen after 1 h. Internalization assays showed maximum internalization after 3 h for all cell lines.

Conclusions

In this work, [89Zr]Zr-DFO-TOC was synthesized with radiochemical yields ≥ 95% and was found to remain stable in vitro at extended time points. In vitro cell studies demonstrated a statistically significant difference between receptor binding and blocking experiments. The development of this work shows potential to positively impact patient care through the predictive dosimetry calculations for the FDA-approved therapeutic agent [177Lu]Lu-DOTA-TATE, while allowing for imaging at extended timepoints and should be studied further.
Control of dengue larvae of Aedes aegypti and Aedes albopictus using the larvicidal bioactive compounds in different plant extracts and plant extract-mediated nanoparticles
Authors: Nawarathne Madhawa Pradeepa , Dharmarathne Chathuranga
Published: December 2024

Background

Dengue is a devastating viral disease transmitted by mosquito vectors of Aedes aegypti and Aedes albopictus. Mosquito populations thrive in favourable breeding conditions, making mosquito control vital. Eliminating larval populations is the most effective method compared with other mosquito control methods. Synthetic chemicals such as organochlorine, organophosphate, carbamate and growth regulators are available for mosquito control, but their use is limited due to health and environmental concerns. Biologically synthesized insecticides are preferable to synthetic insecticides as they are eco-friendly, low cost, target-specific and less toxic for non-target organisms.

Mainbody

Plant-derived bioassays are commonly used to control virally transmitted vectors, as plants contain bioactive compounds such as phytochemicals and essential oils that have high larvicidal efficacy against various mosquito vectors. In addition, nanomaterials are garnering attention in mosquito control due to their eco-friendliness, cost-effectiveness and safety. Commonly used nanomaterials include metal nanoparticles, such as silver nanoparticles, known for their potent larvicidal effect. Nanomaterials can be biologically synthesized through the combination with plant materials and encapsulation of bioactive compounds to maintain their stability and efficacy.

Conclusion

Various plant species and parts, as well as plant-derived nanoparticles, show diverse larvicidal activities against Aedes mosquitos. Among these, plant-mediated nanoparticles demonstrate excellent larvicidal properties against mosquito larvae, including Aedes species.
Plasmodium falciparum with pfhrp2 and pfhrp3 gene deletions in asymptomatic malaria infections in the Lake Victoria region, Kenya
Authors: Okai Takatsugu , Chan Chim W. , KC Achyut , Omondi Protus , Musyoka Kelvin , Kongere James , Kagaya Wataru , Okomo Gordon , Kanoi Bernard N. , Kido Yasutoshi , Gitaka Jesse , Kaneko Akira
Published: December 2024

Malaria rapid diagnostic tests (RDTs) targeting the Plasmodium falciparum histidine-rich protein 2 (PfHRP2) are widely used to diagnose P. falciparum infection. However, reports of P. falciparum strains lacking PfHRP2 and the structurally similar PfHRP3 have raised concerns about the utility and reliability of PfHRP2-based RDTs. This study investigated the presence of P. falciparum with pfhrp2 and/or pfhrp3 gene deletions among infected residents in the Lake Victoria region, Kenya. Four cross-sectional malaria, surveys were conducted in four sites (Suba South, Mfangano, Kibuogi, and Ngodhe) from September 2018 to January 2020. P. falciparum infections were detected using a PfHRP2-based RDT, microscopy, and PCR on 9120 finger-prick blood samples. Samples negative by RDT but positive by PCR were selected for PCR amplification of pfmsp1 and pfmsp2 to confirm the quality and quantity of P. falciparum DNA. Samples positive for both pfmsp1 and pfmsp2 were included for detection of deletions of exons 1 and 2 in pfhrp2 and pfhrp3 PCR. The multiplicity of infection (MOI) was determined as the higher allele count between pfmsp1 and pfmsp2. Logistic regression analysis was performed to analyze the association between pfhrp2 and/or pfhrp3 deletions and demographic and infection variables. Of the 445 RDT-negative and PCR-positive samples, 125 (28.1%) were analyzed for pfhrp2 and pfhrp3 deletions. Single pfhrp2 deletion, single pfhrp3 deletion, and pfhrp2/3 double deletions were detected in 13 (10.4%), 19 (15.2%), and 36 (28.8%) samples, respectively. Single pfhrp2 deletion was found in all sites while single pfhrp3 deletion was found in all sites except Kibuogi. The majority of samples with pfhrp2 and/or pfhrp3 deletions were submicroscopic (73.5%), asymptomatic (80.9%), and monoclonal (80.9%). Polyclonal infection was significantly (p = 0.022) associated with a lower odds of pfhrp2/3 double deletion, suggesting detection of intact pfhrp2/3 in mixed infections. We report the presence of P. falciparum with pfhrp2/pfhrp3 double deletions among asymptomatic and submicroscopic infections in Kenya. Our findings highlight the need for active monitoring of pfhrp2 and pfhrp3 deletions at the community level to improve malaria detection and control in the region.
Validation of prognostic models predicting mortality or ICU admission in patients with COVID-19 in low- and middle-income countries: a global individual participant data meta-analysis
Authors: Damen Johanna A. A. , Arshi Banafsheh , van Smeden Maarten , Bertagnolio Silvia , Diaz Janet V. , Silva Ronaldo , Thwin Soe Soe , Wynants Laure , Moons Karel G. M.
Published: December 2024

Background

We evaluated the performance of prognostic models for predicting mortality or ICU admission in hospitalized patients with COVID-19 in the World Health Organization (WHO) Global Clinical Platform, a repository of individual-level clinical data of patients hospitalized with COVID-19, including in low- and middle-income countries (LMICs).

Methods

We identified eligible multivariable prognostic models for predicting overall mortality and ICU admission during hospital stay in patients with confirmed or suspected COVID-19 from a living review of COVID-19 prediction models. These models were evaluated using data contributed to the WHO Global Clinical Platform for COVID-19 from nine LMICs (Burkina Faso, Cameroon, Democratic Republic of Congo, Guinea, India, Niger, Nigeria, Zambia, and Zimbabwe). Model performance was assessed in terms of discrimination and calibration.

Results

Out of 144 eligible models, 140 were excluded due to a high risk of bias, predictors unavailable in LIMCs, or insufficient model description. Among 11,338 participants, the remaining models showed good discrimination for predicting in-hospital mortality (3 models), with areas under the curve (AUCs) ranging between 0.76 (95% CI 0.71–0.81) and 0.84 (95% CI 0.77–0.89). An AUC of 0.74 (95% CI 0.70–0.78) was found for predicting ICU admission risk (one model). All models showed signs of miscalibration and overfitting, with extensive heterogeneity between countries.

Conclusions

Among the available COVID-19 prognostic models, only a few could be validated on data collected from LMICs, mainly due to limited predictor availability. Despite their discriminative ability, selected models for mortality prediction or ICU admission showed varying and suboptimal calibration.
Impact of eptinezumab on work productivity beyond reductions in monthly migraine days: post hoc analysis of the DELIVER trial
Authors: Barbanti Piero , Awad Susanne F. , Rae-Espinoza Heather , Regnier Stephane A. , Lee Xin Ying , Goadsby Peter J.
Published: December 2024

Background

Eptinezumab’s impact on self-reported work productivity in adults with migraine and 2‒4 prior preventive migraine treatment failures is not fully understood.

Methodology

Electronic diaries captured monthly migraine days (MMDs) reported by patients enrolled in the randomized, double-blind, placebo-controlled DELIVER trial (NCT04418765). The migraine-specific Work Productivity and Activity Impairment questionnaire, administered at baseline and each monthly visit, was a secondary outcome of DELIVER and used to model changes from baseline in self-reported monthly hours of absenteeism (decreased work attendance) and presenteeism (reduced work efficiency while at work with a migraine) in Canada, as the base case. Path analysis illustrated eptinezumab’s impact on work productivity beyond MMDs.

Results

As MMDs increased, monthly hours of absenteeism increased linearly while those of presenteeism increased quadratically. Best-fit models were improved after including an eptinezumab treatment effect, showing benefit over placebo after controlling for MMD frequency. Compared to placebo, patients treated with eptinezumab (pooled) had a modeled reduction from baseline of 7.2 h/month (absenteeism) (95% CI: −9.9, −4.5; P < 0.001) and 21.4 h/month (presenteeism) (95% CI: −26.3, −16.5; P < 0.001) over weeks 1‒24. Beyond MMD reductions, improvements in patient-identified most bothersome symptom (PI-MBS) and reductions in percent of severe migraine attacks contributed to eptinezumab’s effect.

Conclusions

Eptinezumab decreased absenteeism and presenteeism based on patient reports, with data highlighting the importance of considering the PI-MBS. The greater change from baseline than placebo in self-reported absenteeism and presenteeism was only partly explained by changes in MMDs, presenting a potential opportunity to decrease the cost of migraine in the workplace.

Trial registration

ClinicalTrials.gov (Identifier: NCT04418765); EudraCT (Identifier: 2019-004497-25)
Assessing tolerability with the Functional Assessment of Cancer Therapy item GP5: psychometric evidence from LIBRETTO-531, a phase 3 trial of selpercatinib in medullary thyroid cancer
Authors: Regnault Antoine , Bunod Laurine , Loubert Angely , Brose Marcia S. , Hess Lisa M. , Maeda Patricia , Lin Yan , Speck Rebecca M. , Gilligan Adrienne M. , Payakachat Nalin
Published: December 2024

Background

This psychometric analysis generated evidence to support the use of the Functional Assessment of Cancer Therapy item GP5 (GP5) as a measure of tolerability and confirms the appropriateness of categorizing “high side-effect burden” using a rating of 3 or 4 (score ranges 0–4) in patients with advanced/metastatic RET-mutant medullary thyroid cancer (MTC).

Methodology

Blinded, pooled interim data from the safety population (n=290) enrolled in the phase 3 LIBRETTO-531 trial (NCT04211337) were used. Intraclass correlation coefficients (ICC) were calculated for test-retest reliability using data from cycles 1-2 post-baseline. Construct validity was evaluated by examining the correlations of GP5 ratings with (a) symptomatic adverse events (AEs; measured by the PRO-CTCAE), and (b) functioning scores of EORTC QLQ-C30. The ability to detect change over time was examined by Cochrane-Mantel-Haenszel tests for GP5 ratings and PRO-CTCAE. The relationship of “high side-effect burden” categories with QLQ-C30 functioning scores was examined.

Results

ICCs for the GP5 ratings after cycle 1 ranged between 0.80 and 0.85, indicating good reliability. Correlations between GP5 and PRO-CTCAE items ranged from 0.18 to 0.62 and ranged from -0.37 to -0.50 for QLQ-C30 functioning scores, consistent with study assumptions. Post-baseline GP5 ratings showed significant associations with PRO-CTCAE scores (p<0.001). Participants with GP5 ratings of 3 or 4 had worse physical function than those with GP5 ratings of 0 to 2 (p<0.0001).

Conclusions

This analysis generated evidence supportive of the psychometric properties of the GP5 as a fit-for-purpose measure to assess treatment tolerability in patients with advanced/metastatic MTC. The definition of “high side-effect burden” was associated with the clinical feature of tolerability.
Effect of tacrolimus with mycophenolate mofetil or cyclophosphamide on the renal response in systemic lupus erythematosus patients
Authors: Sun Siqin , Zhang Xueyi , Guo Qingqing , Tang Xiaojun , Shen Wei , Liang Jun , Yao Genhong , Geng Linyu , Ding Shuai , Chen Hongwei , Wang Hong , Hua Bingzhu , Zhang Huayong , Feng Xuebing , Jin Ziyi , Sun Lingyun
Published: December 2024

Objective

This study aimed to determine the therapeutic efficacy of tacrolimus (TAC) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) on the renal response in systemic lupus erythematosus (SLE) patients.

Methods

A retrospective cohort study based on medical data was conducted among SLE patients who took at least one of the following medicines in 2010–2021: TAC, MMF and CYC. The odds ratio (OR) and 95% confidence interval (CI) were calculated, and the synergistic interaction was estimated using logistic regression models.

Results

Among 793 SLE patients, 27.9% patients (221 cases) achieved CR after at least 3 months. The TAC use was positively associated with CR with an adjusted OR (95% CI) of 2.82 (1.89, 4.22) overall and in subgroups of SLE patients with SLEDAI scores > 12, moderate or severe urinary protein and comorbidities. The dose-response effect on CR was also observed at TAC doses greater than 4 mg/d and more than 180 days, with adjusted ORs (95% CIs) of 5.65 (2.35, 13.55) and 3.60 (2.02, 6.41), respectively. Moreover, the combined effect of TAC with MMF or CYC was better than that of monotherapy, there was significant synergistic interactions with adjusted ORs (95% CIs) of 2.43 (1.20, 4.92) and 3.14 (1.49, 6.64), respectively, and similar results were observed for the combination of different doses of TAC with MMF or CYC.

Conclusion

TAC can effectively alleviate the condition of patients with SLE and may interact with MMF or CYC, which suggests that the combination therapy of TAC with MMF or CYC may produce greater benefits for patients with SLE.

Trial registration

This is a purely observational study that does not require registration.
Insecticidal potential of botanical extracts for management of, the oriental fruit fly, Bactrocera dorsalis (Diptera: Tephritidae)
Authors: Akram Wasim , Hussain Azhar , Abbas Qamar , Abbas Aqleem
Published: December 2024

Background

Bactrocera dorsalis (Hendel) poses a significant threat to global fruit production and quality, including in Pakistan, where it causes substantial losses. Traditional control methods have heavily relied on the indiscriminate and imprudent use of insecticides, leading to challenges such as insecticide resistance, environmental pollution, fruit contamination, and health risks. This study explores the insecticidal potential of seven selected botanicals: Artemisia vulgaris L., Capparis spinosa L., Mentha longifolia, Mentha piperita, Peganum harmala, Eucalyptus globulus, and Callistemon viminalis, each at three different concentrations (10mL, 20mL, and 30mL), against Bactrocera dorsalis (B. dorsalis). Two in vitro experiments involving the application of plant extracts mixed with protein bait and direct spray were conducted.

Results

Both experimental results demonstrated a direct correlation between the concentration of plant extract and the mortality of B. dorsalis. In the plant extract mixed with protein bait, results recorded after 96 h at 10 mL ranged from 8.667 ± 1.52–47.000 ± 3.00, at 20 mL from 18.667 ± 1.52–53.667 ± 6.02, and 30 mL from 26.000 ± 5.29- 67.667 ± 2.08. Meanwhile, for direct spray, mortality ranged from 2.333 ± 1.15–32.333 ± 6.80 at 10 mL, 1.000 ± 1.00–42.667 ± 7.02 at 20 mL, and 9.667 ± 2.30–61.333 ± 8.50 at 30 mL, respectively. The plant species exhibiting the highest toxic potential against the respective pests was C. viminalis, followed by A. vulgaris L. In contrast, the least toxic effect was observed in Eucalyptus globulus at all concentrations. The highest mean mortality and repellence % were recorded in C. viminalis and E. globulus in both experimental trials. The results revealed the highest efficacy of C. viminalis with an LC50 value of 9685.15 and 19,909.11 ppm, for the extract mixed with protein bait and sprayed, was obtained, respectively, the most toxic to the pest followed by the extracts E. globulus and C. spinosa L.

Conclusion

Based on our experimental results, it is concluded that C. viminalis and A. vulgaris L. are an effective alternative for the management of B. dorsalis.
Risk factors and comorbidities associated with cardiac arrests and medical emergencies in interventional radiology patients
Authors: AlHarbi Husam Mohammed , Arabi Tarek , Alduribi Yasser Saleh A. , Shah Hassan , Sabbah Ahmad , Othman Khalid , Bashir Omar , Arabi Mohammad
Published: December 2024

Purpose

To investigate the incidence, predictors, and outcomes of medical emergencies in patients undergoing IR procedures at a tertiary care center.

Materials and methods

Seven-year retrospective review of all medical emergencies in patients undergoing IR procedures at King Abdulaziz Medical City, Riyadh, Saudi Arabia. Medical emergencies included Cardiopulmonary arrest (CPA), or emergencies that required activation of the critical care response team (CCRT). Variables included demographics, procedure details and outcome data including complications and 30-day mortality. Multivariate logistic regression analysis was conducted to identify independent predictors of CPA and 30-day mortality.

Results

Ninety-four patients (50% male) were included with a median age of 60.5 years. Recent or current ICU admission was recorded in 39 patients (43.8%). Comorbidities included diabetes (50%), hypertension (59.6%), coronary artery disease (25.5%), heart failure (21.5%), ESRD (28.7%), active infection 28 (31%), with ASA3 in 64 patients (68%) and ASA4 in 23 (24.5%).

The incidence of CPA and CCRT activation was 0.045% and 0.049%, respectively, among 100,000 patients who underwent IR procedures during the study period. Half the events were with venous procedures, followed by non-vascular (33%) and arterial procedures (10.6%). 30-day mortality was 30.5%. Independent predictors of CPA included pulmonary disease (aOR 16.79, 95% CI 2.334–195.3, p = 0.0097), emergency procedures (aOR 11.63, 95% CI 2.517–72.46, p = 0.0035), general anesthesia (aOR 19.41, 95% CI 1.854–491.8, p = 0.0254), and sedation (aOR 13.04, 95% CI 2.081–118.8, p = 0.0108). Predictors of 30-day mortality were CPA (aOR 9.830, 95% CI 2.439–66.66, p = 0.0045) and hypotension as a complication (aOR 16.81, 95% CI 3.766–122.3, p = 0.0009).

Conclusion

Our findings highlight the complexity of patients undergoing IR procedures and the importance of identifying high-risk patients to prevent adverse events in the IR setting.
Aggravated liver steatosis in a modern dietary mouse model via long-term treatment of SiO2 nanoparticles in drinking water
Authors: Ye Tzung Cheng , Chao Shu-Ju , Huang Chihpin , Mai Ru-Tsun
Published: December 2024

SiO2 nanoparticles (SNPs), which are abundant in water and are used for various applications, for example, as food additives and anticaking agents, are of growing concern because of rising exposure to human health. Research has reported low potential side effects in animal models treated with SNPs; however, a few in vivo studies have shown cause for concern. Presently, high-fat foods have changed our lives and increased the incidence rates of fatty liver, obesity, and overweight, and high-fat foods issue is prevalent in our modern society. To understand the rising SNPs exposure in life and modern dietary habits combined effect, we design experiments to study this research.

Institute of Cancer Research mice fed a normal or high-fat diet were treated with different concentrations of SNPs for long-term effects. Blood and liver tissue were collected and prepared for blood biochemical assays, histology analysis, silicon and triglycerides (TGs) accumulation, immunohistochemistry, fibrosis staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining to analyze the influence of the combination of SNPs and a high-fat diet.

 This research found that the presence of SNPs in drinking water with the consumption of a high-fat diet was associated with the accumulation of SNPs and TGs in liver tissue, elevated aspartate aminotransferase and alanine aminotransferase levels in serum, activation of fibrosis and inflammation, increased oxidative stress through 4-hydroxynonenal, and the development of liver steatosis. The results showed that the long-term effect of SNPs in drinking water might induce liver steatosis, particularly under modern dietary habits such as a high-fat diet. This study investigated the interactions between environmental nanoparticles, such as the long-term risk of exposure to SNPs, and dietary factors, suggesting a significant risk to liver health, especially in human health.
A conceptual modeling approach of MQTT for IoT-based systems
Authors: Mohammad El-Basioni Basma M.
Published: December 2024

The Message Queuing Telemetry Transport (MQTT) is one of the most commonly used standard messaging protocols that enable the Internet of Things (IoT). The messaging standard specification document defines the transactions, attributes, conventions, timers, values, types, structures, etc. MQTT encounters wide implementation possibilities: hardware vendors need to implement MQTT drivers for their devices, software vendors need to implement it in their solutions, developers and researchers need an MQTT simulation framework, etc. The IoT technology can enable unlimited number of use cases, and each case has its implementation of the messaging protocol. From the above facts, on the basis that any user needs to have a deep understanding of the specification in order to implement the protocol and also developers need to study it well for improving the protocol, there is a need for a standard conceptual way that conveys the messaging standard specifications, integrates the specifications of the use cases built upon with a more abstracted mental representation, improves the communication between developers, and facilitates the protocols and applications developments. This paper addresses this issue by proposing a graphical conceptual modeling approach for MQTT-based IoT applications called Example-oriented System Conceptual Modeling for MQTT use cases (EoSCM-MQTT). The paper explains the EoSCM-MQTT and gives an example of its use in an MQTT simulation implementation for a specific IoT application: smart parking. EoSCM-MQTT was validated using three methods: comparison, analysis, and implementation. The details and results of the implementation and the conclusions from the comparison and analysis indicated that EoSCM-MQTT has the required characteristics of conceptual models: good syntactic semantic, and pragmatic quality, clarity, coherence, accuracy, flexibility, reliability, and effectiveness.