bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of a City’s Healthcare Resources on Immigrants’ Employment Quality
Authors: Li Ping , Wang Ziqi , Zhao Liting
Published: August 2024

This study investigates the impact of city healthcare resources on immigrants’ employment quality. It has implications for promoting equity in the distribution of healthcare resources, which is critical for immigrants’ survival and settlement. Moreover, the relationship between healthcare resources and employment quality is equally relevant to developing-country urbanization. Using data from the China Migrants Dynamic Survey (CMDS) from 2016 to 2018, we demonstrate the effect of healthcare resources on employment quality. Cities’ healthcare resources are significantly correlated with immigrants’ quality of employment. The more healthcare resources are available, the higher the income from work, the shorter the working hours, and the more stable the employment of immigrants. The quality-enhancing effect of healthcare resources on employment quality is substantial among immigrants with health training and medical files. Urban medical insurance has important differentiating implications for immigrants’ access to healthcare resources. Healthcare resources enhance the employment quality of immigrants by improving their health status and integration into local society. Promoting equalizing healthcare resources and adjusting the differences between urban and rural medical insurance systems increase immigrant employment quality.
Dissemination and implementation science frameworks and strategies to increase breast cancer screening for at-risk women in the United States: A scoping review
Authors: Rao Meera , Densley Sebastian , Marciniak Adeife , Burgoa Sara , Zerrouki Yasmine , Okwaraji Goodness , Lobaina Diana , Jhumkhawala Vama , Knecht Michelle , Kitsantas Panagiota , Sacca Lea
Published: August 2024

Dissemination and implementation science (D&I) can help bridge the gap between research and practice by addressing how to facilitate and maintain pre-existing evidence-based interventions (EBIs) in various contexts within different fields, including that of breast cancer screening and treatment. Yet, despite the availability of D&I frameworks and strategies, there is a lack of studies exploring knowledge transfer dissemination and implementation models, strategies, and frameworks in the setting of breast cancer care. There is a need for studies that create guidelines and roadmaps built on theoretical foundations of D&I research to scale up successful D&I of strategies, frameworks, and protocols proven to cater to the needs of all breast cancer patients when seeking screening and treatment services. The Arksey and O’Malley (2005) York methodology was used as guidance for this review: (1) identifying research questions; (2) searching for relevant studies; (3) selecting studies relevant to the research questions; (4) charting the data; (5) collating, summarizing, and reporting results. Most cited barriers ( n = 46) sorted into the category of “Recruitment, Measurement, and Delivery Challenges.” The predominant ERIC strategy, featured in a noteworthy 84% of studies, was “Tailor strategies” (#16), which belongs to the “Adapt and tailor to context: culture, language, data analysis, collection” domain. This study can guide researchers, physicians, and community workers in improving accessibility, affordability, and quality of breast cancer screening and adequate follow-up opportunities through D&I strategies and models improving the reach and sustainability of evidence-based programs in at-risk female populations.
The Merits of Bilateral Application of Middle Ear Implants in Patients With Bilateral Conductive and/or Mixed Hearing Loss
Authors: Agterberg Martijn J.H. , Straatman Louise , Bruchhage Karl-Ludwig , Jürgens Tim , Hollfelder Daniela , Leichtle Anke
Published: August 2024

This study investigated sound localization abilities in patients with bilateral conductive and/or mixed hearing loss (BCHL) when listening with either one or two middle ear implants (MEIs). Sound localization was measured by asking patients to point as quickly and accurately as possible with a head-mounted LED in the perceived sound direction. Loudspeakers, positioned around the listener within a range of +73°/−73° in the horizontal plane, were not visible to the patients. Broadband (500 Hz–20 kHz) noise bursts (150 ms), roved over a 20-dB range in 10 dB steps was presented. MEIs stimulate the ipsilateral cochlea only and therefore the localization response was not affected by crosstalk. Sound localization was better with bilateral MEIs compared with the unilateral left and unilateral right conditions. Good sound localization performance was found in the bilaterally aided hearing condition in four patients. In two patients, localization abilities equaled normal hearing performance. Interestingly, in the unaided condition, when both devices were turned off, subjects could still localize the stimuli presented at the highest sound level. Comparison with data of patients implanted bilaterally with bone-conduction devices, demonstrated that localization abilities with MEIs were superior. The measurements demonstrate that patients with BCHL, using remnant binaural cues in the unaided condition, are able to process binaural cues when listening with bilateral MEIs. We conclude that implantation with two MEIs, each stimulating only the ipsilateral cochlea, without crosstalk to the contralateral cochlea, can result in good sound localization abilities, and that this topic needs further investigation.
Enabling Creative Destruction: A View from the Perspective of Managerial Control
Authors: Chanda Sasanka Sekhar
Published: August 2024

Creative destruction originates in successful development and launch of a radically different product/process/market configuration, or radical innovation, by a company. A radical innovation can materialize in a business firm only if autonomy is extended to organizational personnel, towards experimentation with heterogeneous knowledge from outside the organization. In this article, I inquire into conditions that enable the materialization of radical innovation—an important precursor to creative destruction—while affording top management the wherewithal to stay in control. An extended version of March’s computational model suggests that when a radical innovation project initiates with a low level of collective human capital with respect to the new process–product–market domain being considered and the project personnel are provided a certain extent of autonomy to experiment in the new domain, top management can detect a change to organizational outcomes by changing the rate of exploitation. Thereby top management obtains a feeling of being in control of proceedings. This situation is, therefore, conducive to the materialization of creative destruction. The indirect method of control to nurture radical innovation—demonstrated in this research—constitutes an improvement over the autonomy-averse ‘agency’ and ‘transaction cost economics’ approaches that are sub-optimal in open systems characterizing radical innovation efforts in corporate venturing.
The Impacts on Interorganizational Project Coordination: A Multiple Case Study on Large Railway Projects
Authors: Trauernicht Nina , Braaksma Jan , Haanstra Willem , van Dongen Leo A.M.
Published: August 2024

Interorganizational transportation projects are increasingly difficult to manage because of a need to coordinate complex interdependencies pertaining to railway organizations with increasing levels of connectedness. In this article, the perceived dynamics of coordination mechanisms in the decision-making processes of interorganizational projects of the Dutch railway system are investigated. The results of this study suggest that the perceived effectiveness of interorganizational decision-making can be positively impacted during the pre-project phase, by emphasizing relational coordination. A reinforcing relationship between trust and mutual understanding among stakeholders by means of relational coordination mechanisms is one explored explanation.
Projects as Vectors of Change: A Transition Toward Net-Zero Sociotechnical Systems
Authors: Terenzi Marco , Locatelli Giorgio , Winch Graham M.
Published: August 2024

Projects are essential for the net-zero transition, yet the project studies literature largely ignores net-zero transition and net-zero projects. We argue that projects are vectors of change enabling the transition toward net-zero sociotechnical systems. Leveraging a systematic literature review, we identify four types of net-zero projects: (1) new assets; (2) upgrade assets; (3) behavioral intervention; and (4) Research, Development, and Demonstration (RDD). We present how “net-zero projects” can enable the transition of sociotechnical systems toward net-zero, reducing emission intensity or quantity. Finally, we underline the heterogeneity of net-zero projects in terms of complexity, barriers, benefits realization time span, and complementarities.
GLUT5-overexpression-related tumorigenic implications
Authors: Hadzi-Petrushev Nikola , Stojchevski Radoslav , Jakimovska Anastasija , Stamenkovska Mimoza , Josifovska Slavica , Stamatoski Aleksandar , Sazdova Iliyana , Sopi Ramadan , Kamkin Andre , Gagov Hristo , Mladenov Mitko , Avtanski Dimiter
Published: August 2024

Glucose transporter 5 (GLUT5) overexpression has gained increasing attention due to its profound implications for tumorigenesis. This manuscript provides a comprehensive overview of the key findings and implications associated with GLUT5 overexpression in cancer. GLUT5 has been found to be upregulated in various cancer types, leading to alterations in fructose metabolism and enhanced glycolysis, even in the presence of oxygen, a hallmark of cancer cells. This metabolic shift provides cancer cells with an alternative energy source and contributes to their uncontrolled growth and survival. Beyond its metabolic roles, recent research has unveiled additional aspects of GLUT5 in cancer biology. GLUT5 overexpression appears to play a critical role in immune evasion mechanisms, which further worsens tumor progression and complicates therapeutic interventions. This dual role of GLUT5 in both metabolic reprogramming and immune modulation highlights its significance as a potential diagnostic marker and therapeutic target. Understanding the molecular mechanisms driving GLUT5 overexpression is crucial for developing targeted therapeutic strategies that can disrupt the unique vulnerabilities of GLUT5-overexpressing cancer cells. This review emphasizes the complexities surrounding GLUT5’s involvement in cancer and underscores the pressing need for continued research to unlock its potential as a diagnostic biomarker and therapeutic target, ultimately improving cancer management and patient outcomes.
The role of kynurenines in migraine-related neuroimmune pathways
Authors: Körtési Tamás , Nagy-Grócz Gábor , Vécsei László
Published: August 2024

Migraine, a primary headache disorder whose mechanism remains incompletely understood, appears to involve the activation of the trigeminovascular system (TS) during attacks. Research suggests that inflammatory processes mediated by the immune system may play a role in migraine pathophysiology. Neuroinflammation is often associated with migraine attacks, with cytokines serving as crucial mediators in the process. Elevated levels of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), have been observed in the blood and cerebrospinal fluid of individuals experiencing migraine attacks. These cytokines have the capacity to sensitize pain pathways in the brain, thereby increasing sensitivity to pain stimuli. This phenomenon, known as central sensitization, is believed to contribute to the intensity and persistence of migraine pain. Kynurenines, endogenous mediators of glutamatergic mechanisms, can significantly influence the pathophysiology of primary headache disorders. The kynurenine system is collectively known as the kynurenine pathway (KP), which can act on multiple receptors, such as glutamate receptors, aryl hydrocarbon receptors (AhRs), G protein-coupled receptors 35 (GPR35), and α-7 nicotinic acetylcholine (α7 nACh) receptors. These receptors are also found on various cells of the immune system, so the role of the KP in the pathomechanism of primary headaches may also be mediated through them. In this review, our goal is to show a possible link between the receptors of the KP and immune system in the context of inflammation and migraine. Migraine research in recent years has focused on neuropeptides, such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as potential pathogenic factors and possible therapeutic approaches. These peptides share many similarities in their characteristics and roles. For instance, they exhibit potent vasodilation, occur in both the peripheral and central nervous systems, and play a role in transmitting nociception and neurogenic inflammation. The investigation of potential connections between the aforementioned neuropeptides and the kynurenine pathway could play a significant role in uncovering the pathomechanism of migraine and identifying new drug candidates.
Nanomaterial-based sensors for microbe detection: a review
Authors: Khan Muhammad Qamar , Khan Jahangir , Alvi Muhammad Abbas Haider , Nawaz Hifza , Fahad Muhammad , Umar Muhammad
Published: August 2024

Airborne microorganisms pose a significant health threat, causing various illnesses. Traditional detection methods are often slow and complex. This review highlights the potential of nanomaterial-based biosensors, particularly colorimetric sensors, for rapid and on-site detection of airborne microbes. Colorimetric sensors offer real-time visual detection without complex instrumentation. We explore the integration of these sensors with Lab-on-a-Chip technology using PDMS microfluidics. This review also proposes a novel PDMS-based colorimetric biosensor for real-time detection of airborne microbes. The sensor utilizes a color change phenomenon easily observable with the naked eye, simplifying analysis and potentially enabling point-of-care applications.

Graphical Abstract
Rectus abdominis muscle flap in complex vesico-vaginal fistula repair: unique situation, uncommon option
Authors: Aravind T. K. , Yadav Siddharth , Singh Harshdeep
Published: August 2024

Background

Complex vesico-vaginal fistulae (VVF) pose unique surgical challenges and necessitate the use of interposition tissue to ensure surgical success. Herein, we describe a case of complex VVF with right uretero-vaginal fistula post radical surgery for locally advanced ovarian cancer and chemotherapy in which the rectus abdominis muscle flap was used as the interposition tissue, as the more routine used options such as omentum and peritoneum were removed in the prior radical surgery.

Case presentation

We describe a case report of a vesico-vaginal and right uretero-vaginal fistula in a 34-year-old female post ovarian cancer radical surgery managed surgically with the traditional transvesical technique of repair and ureteric reimplantation with a unique interposition with rectus abdominis muscle considering the absence of the more routine options.

Conclusion

Complex VVFs pose unique surgical challenges and necessitate the use of interposition tissue to ensure surgical success. The inferior pedicle based rectus abdominis muscle flap is an excellent interposition tissue for repairs via the transabdominal approach especially in scenarios where the more routine options are unavailable.
Few chemoreceptor genes in the ambrosia beetle Trypodendron lineatum may reflect its specialized ecology
Authors: Biswas Twinkle , Vogel Heiko , Biedermann Peter H. W. , Lehenberger Maximilian , Yuvaraj Jothi Kumar , Andersson Martin N.
Published: August 2024

Background

Chemoreception is crucial for insect fitness, underlying for instance food-, host-, and mate finding. Chemicals in the environment are detected by receptors from three divergent gene families: odorant receptors (ORs), gustatory receptors (GRs), and ionotropic receptors (IRs). However, how the chemoreceptor gene families evolve in parallel with ecological specializations remains poorly understood, especially in the order Coleoptera. Hence, we sequenced the genome and annotated the chemoreceptor genes of the specialised ambrosia beetleTrypodendron lineatum(Coleoptera, Curculionidae, Scolytinae) and compared its chemoreceptor gene repertoires with those of other scolytines with different ecological adaptations, as well as a polyphagous cerambycid species.

Results

We identified 67 ORs, 38 GRs, and 44 IRs inT. lineatum(‘Tlin’). Across gene families,T. lineatumhas fewer chemoreceptors compared to related scolytines, the coffee berry borerHypothenemus hampeiand the mountain pine beetleDendroctonus ponderosae, and clearly fewer receptors than the polyphagous cerambycidAnoplophora glabripennis. The comparatively low number of chemoreceptors is largely explained by the scarcity of large receptor lineage radiations, especially among the bitter taste GRs and the ‘divergent’ IRs, and the absence of alternatively spliced GR genes. Only one non-fructose sugar receptor was found, suggesting several sugar receptors have been lost. Also, we found no orthologue in the ‘GR215 clade’, which is widely conserved across Coleoptera. Two TlinORs are orthologous to ORs that are functionally conserved across curculionids, responding to 2-phenylethanol (2-PE) and green leaf volatiles (GLVs), respectively.

Conclusions

Trypodendron lineatumreproduces inside the xylem of decaying conifers where it feeds on its obligate fungal mutualistPhialophoropsis ferruginea.Like previous studies, our results suggest that stenophagy correlates with small chemoreceptor numbers in wood-boring beetles; indeed, the few GRs may be due to its restricted fungal diet. The presence of TlinORs orthologous to those detecting 2-PE and GLVs in other species suggests these compounds are important forT. lineatum. Future functional studies should test this prediction, and chemoreceptor annotations should be conducted on additional ambrosia beetle species to investigate whether few chemoreceptors is a general trait in this specialized group of beetles.
Predicting incident radiographic knee osteoarthritis through quantitative meniscal lesion parameters: data from the osteoarthritis initiative
Authors: Bo Kaida , Xie Xiangpeng , Liu Xin , Ou Jianliang , Zhang Yuanyi , Wang Xu , Yang Shuo , Zhang Wei , Zhang Lelei , Chang Jun
Published: August 2024

Background

This study investigates the potential of novel meniscal parameters as predictive factors for incident radiographic knee osteoarthritis (ROA) over a span of four years, as part of the Osteoarthritis Initiative (OAI) study.

Objectives

Quantitative measurements of meniscal parameters alteration could serve as predictors of OA’s occurrence and progression.

Methods and materials

A nested matched case-control study design was used to select participants from OAI study. Case knees (n = 178) were defined as those with incident ROA (Kellgren Lawrence Grade (KLG) 0 or 1 at baseline (BL), evolving into KLG 2 or above by year 4). Control knees were matched one-to-one by sex, age and radiographic status with case knees. The mean distance from medial-to-lateral meniscal lesions [Mean(MLD)], mean value of tibial plateau width [Mean(TPW)] and the mean of the relative percentage of the medial-to-lateral meniscal lesions distance [Mean(RMLD)] were evaluated through coronal T2-weighted turbo spin echo (TSE) MRI at P-0 (visit when incident ROA was found on radiograph), P-1(one year prior to P-0) and baseline, respectively. Using the imaging data of one patient, the mechanism was investigated by finite element analysis.

Results

Participants were on average 60.22 years old, predominantly female (66.7%) and overweight (mean BMI: 28.15). Mean(MLD) and Mean(RMLD) were significantly greater for incident knees compared to no incident knees at baseline, P-1 and P-0. [Mean(MLD), Mean(RMLD); (42.56–49.73) mean ± (7.70–9.52) mm SD vs. (38.14–40.78) mean ± (5.51–7.05)mm SD; (58.61–68.95) mean ± (8.52–11.40) mm SD vs. (52.52–56.35) mean ± (6.53–7.85)mm SD, respectively]. Baseline Mean(MLD) and Mean(RMLD), [Adjusted OR, 95%CI: 1.11(1.07 to 1.16) and 1.13(1.09 to 1.17), respectively], were associated with incident ROA during 4 years, However, Mean(TPW) [Adjusted OR, 95%CI: 0.98(0.94 to 1.02)] was not associated with incident ROA during 4 years. While Mean(TPW) at P-1 and P-0 was not associated with the risk of incident ROA, Mean(MLD) and Mean(RMLD) at P-1 and P-0 were significantly positively associated with the risk of incident ROA.

Conclusions

The meniscal parameters alteration could be an important imaging biomarker to predict the occurrence of ROA.
The efficacy and potential mechanisms of pyrotinib in targeting EGFR and HER2 in advanced oral squamous cell carcinoma
Authors: Zhou Liang , Le Kehao , Chen Qianming , Wang Huiming
Published: August 2024

Background

Human epidermal growth factor receptor 2 (HER2) plays an important role in the progression of multiple solid tumors and induces resistance to epidermal growth factor receptor (EGFR) target treatment. However, the expression status and the clinical significance of HER2 in oral squamous cell carcinoma (OSCC) is still controversial. Pyrotinib (PYR) is a promising novel EGFR/HER2 dual inhibitor, whose efficacy in OSCC has not been determined.

Methods

57 locally advanced de novo OSCC patients were included in this study to investigate the relationship between the HER2 expression levels and the prognosis by the tissue microarray analysis (TMA). In vitro and in vivo experiments were performed to retrieve the efficacy of PYR in OSCC. The main downstream of HER2 was evaluated by western blotting in OSCC cell lines and xenograft tumors to explore the potential mechanism of PYR.

Results

This study revealed the primary tumor of OSCC had higher HER2 expression levels. Patients with HER2 overexpression had poor overall survival (P < 0.014) and poor disease free survival (P < 0.042). In vitro, PYR suppressed the proliferation, colony formation and migration of OSCC cells. It also promoted apoptosis of OSCC cells and induced cell cycle arrest. Furthermore, PYR was able to inhibit the occurrence and development of OSCC effectively in vivo. Western blotting revealed that PYR suppressed OSCC by inhibiting the phosphorylation of HER2, AKT and ERK.

Conclusions

This study exhibited the anti-OSCC effects of PYR in vitro and in vivo, and demonstrated PYR inhibited OSCC cells by inducing apoptosis via the HER2/ AKT and ERK pathway. The result of this study also indicated locally advanced OSCC patients might benefit from HER2 assay and EGFR/HER2 dual inhibit treatment.
Effect of the use of remineralization agents before resin infiltration on the treatment of initial enamel lesions: an in-vitro study
Authors: Doğu Kaya Bengü , Manav Özen Aybike , Yılmaz Atalı Pınar , Sarıalioğlu Güngör Ayça , Dalkılıç Evrim , Alkan Elif , Tağtekin Dilek , Türkmen Cafer
Published: August 2024

Aim

This study aimed to evaluate the effect of the use of remineralization agents before the application of resin infiltration on the treatment of initial enamel lesions.

Materials and methods

Eighty buccal enamel samples were prepared from human molars, and artificial initial lesions were formed after 96 h of incubation with a demineralizing solution. The samples were randomly divided into 8 groups (n = 10) including a remineralizing agent (Tooth Mousse, Medical Mineral Gel, Remin Pro), resin infiltration (ICON), and a combined treatment of both. Remineralizing agents were applied in pH cycle for 7 days. Baseline, demineralization, and after-treatment fluorescence (FluoreCam and DIAGNOdent Pen), surface microhardness (HMV-2T), surface roughness (M300C), OCT (Maestro-2) and ultrasonic system (Novascope 4500) data were obtained for all groups. The sample surfaces were examined under SEM/EDX (SU3500) at x1000. Data were statistically analyzed using the Two-Way Robust ANOVA and Bonferroni tests (p < 0.05).

Results

There was no statistically significant difference between the groups for microhardness, roughness, OCT, DIAGNOdent Pen, ultrasound, and FluoreCam size/intensity values (p = 0.582; p = 0.963; p = 0.884; p = 0.923; p = 0.051; p = 0.268; p = 0.793 respectively). The effect of the treatment procedure showed a significant difference (p < 0.001), except for the roughness values (p = 0.984). The lowest Calcium (Ca) ratio (%atomic) was observed in the RI group in the EDX analysis.

Conclusion

Remineralizing agents and resin infiltration methods may be used in combination or alone in the treatment of initial enamel lesions. Combining remineralizing agents with resin infiltration does not alter the efficacy of the treatment.
Competencies required to make use of Information Science and Technology among Japanese medical students: a cross-sectional study
Authors: Ota Yuma , Asada Yoshikazu , Mieno Makiko , Matsuyama Yasushi
Published: August 2024

Background

Competency in the use of information science and technology (IST) is essential for medical students. This study identified learning objectives and competencies that correspond with low self-assessment related to use of IST and factors that improve such self-assessment among medical students.

Methods

A questionnaire was administered to sixth-year medical students across 82 medical schools in Japan between November 2022 and February 2023.

Results

Three learning objectives were identified as difficult for the students to achieve: (1) provide an overview of the regulations, laws, and guidelines related to IST in medicine; (2) discuss ethical issues, such as social disparities caused by the digital divide that may arise in the use of IST in medicine; and (3) understand IST related to medical care. Further, problem-based learning, engaging with IST beyond class, and learning approach impacted the students’ acquisition of competencies related to IST. Furthermore, it was recognized that the competencies required by medical students may change over the course of an updated medical school curriculum.

Conclusions

It is important for medical students to recognize the significance of learning, establishing active learning methods, and gaining experience in practically applying these competencies.
Inversion-recovery ultrashort-echo-time (IR-UTE) MRI-based detection of radiation dose heterogeneity in gynecologic cancer patients treated with HDR brachytherapy
Authors: Sheikh Khadija , Daniel Bruce L. , Roumeliotis Michael , Lee Junghoon , Hrinivich William T. , Benkert Thomas , Bhat Himanshu , Seethamraju Ravi T. , Viswanathan Akila N. , Schmidt Ehud J.
Published: August 2024

Purpose

To evaluate the relationship between delivered radiation (RT) and post-RT inversion-recovery ultrashort-echo-time (IR-UTE) MRI signal-intensity (SI) in gynecologic cancer patients treated with high-dose-rate (HDR) brachytherapy (BT).

Methods

Seven patients underwent whole-pelvis RT (WPRT) followed by BT to the high-risk clinical target volume (HR-CTV). MR images were acquired at three time-points; pre-RT, post-WPRT/pre-BT, and 3–6 months post-BT. Diffuse-fibrosis (FDiffuse) was imaged with a non-contrast dual-echo IR (inversion time [TI] = 60 ms) UTE research application, with image-subtraction of the later echo, only retaining the ultrashort-echo SI. Dense-fibrosis (FDense) imaging utilized single-echo Late-Gadolinium-Enhanced IR-UTE, acquired ∼ 15 min post-Gadavist injection. Resulting FDiffuse and FDense SI were normalized to the corresponding gluteal-muscle SI. Images were deformably registered between time-points based on normal tissue anatomy. The remnant tumor at both time-points was segmented using multi-parametric MRI. Contours corresponding to the 50%, 100%, 150%, and 200% isodose lines (IDLs) of the prescription BT-dose were created. Mean FDiffuse and FDense SI within (i) each IDL contour and (ii) the remnant tumor were calculated. Post-BT FDiffuse and FDense SI were correlated with prescribed BT-dose. To determine the relationship between BT-dose and IR-UTE SI, the differences in the post-BT FDense across IDLs was determined using paired t-tests with Bonferroni correction.

Results

FDense was higher in regions of higher dose for 6/7 patients, with mean ± SD values of 357 ± 103% and 331 ± 97% (p = .03) in the 100% and 50% IDL, respectively. FDense was higher in regions of higher dose in the responsive regions with mean ± SD values of 380 ± 122% and 356 ± 135% (p = .03) in the 150% and 50% IDL, respectively. Within the segmented remnant tumor, an increase in prescribed dose correlated with an increase in FDense post-BT (n = 5, r = .89, p = .04). Post-BT FDiffuse inversely correlated (n = 7, r = -.83, p = .02) with prescribed BT-dose within the 100% IDL.

Conclusions

Results suggest that FDense SI 3–6 months post-BT is a sensitive measure of tissue response to heterogeneous BT radiation-dose. Future studies will validate whether FDiffuse and FDense are accurate biomarkers of fibrotic radiation response.
Network proteomics of the Lewy body dementia brain reveals presynaptic signatures distinct from Alzheimer’s disease
Authors: Shantaraman Anantharaman , Dammer Eric B. , Ugochukwu Obiadada , Duong Duc M. , Yin Luming , Carter E. Kathleen , Gearing Marla , Chen-Plotkin Alice , Lee Edward B. , Trojanowski John Q. , Bennett David A. , Lah James J. , Levey Allan I. , Seyfried Nicholas T. , Higginbotham Lenora
Published: August 2024

Lewy body dementia (LBD), a class of disorders comprising Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB), features substantial clinical and pathological overlap with Alzheimer’s disease (AD). The identification of biomarkers unique to LBD pathophysiology could meaningfully advance its diagnosis, monitoring, and treatment. Using quantitative mass spectrometry (MS), we measured over 9,000 proteins across 138 dorsolateral prefrontal cortex (DLPFC) tissues from a University of Pennsylvania autopsy collection comprising control, Parkinson’s disease (PD), PDD, and DLB diagnoses. We then analyzed co-expression network protein alterations in those with LBD, validated these disease signatures in two independent LBD datasets, and compared these findings to those observed in network analyses of AD cases. The LBD network revealed numerous groups or “modules” of co-expressed proteins significantly altered in PDD and DLB, representing synaptic, metabolic, and inflammatory pathophysiology. A comparison of validated LBD signatures to those of AD identified distinct differences between the two diseases. Notably, synuclein-associated presynaptic modules were elevated in LBD but decreased in AD relative to controls. We also found that glial-associated matrisome signatures consistently elevated in AD were more variably altered in LBD, ultimately stratifying those LBD cases with low versus high burdens of concurrent beta-amyloid deposition. In conclusion, unbiased network proteomic analysis revealed diverse pathophysiological changes in the LBD frontal cortex distinct from alterations in AD. These results highlight the LBD brain network proteome as a promising source of biomarkers that could enhance clinical recognition and management.
Research progress of brain organoids in the field of diabetes
Authors: Su Ying , Liu Aimei , Chen Hongguang , Chen Qingjie , Zhao Bo , Gao Runze , Zhang Kangwei , Peng Tie , Zhang Zhenwang , Ouyang Changhan , Zhu Dan
Published: August 2024

Human embryonic stem cells and human induced pluripotent stem cells may be used to create 3D tissues called brain organoids. They duplicate the physiological and pathological characteristics of human brain tissue more faithfully in terms of both structure and function, and they more precisely resemble the morphology and cellular structure of the human embryonic brain. This makes them valuable models for both drug screening and in vitro studies on the development of the human brain and associated disorders. The technical breakthroughs enabled by brain organoids have a significant impact on the research of different brain regions, brain development and sickness, the connections between the brain and other tissues and organs, and brain evolution. This article discusses the development of brain organoids, their use in diabetes research, and their progress.
Progesterone boosts abiraterone-driven target and NK cell therapies against glioblastoma
Authors: Chen Hsien-Chung , Lin Hong-Yi , Chiang Yung-Hsiao , Yang Wen-Bin , Wang Chung-Han , Yang Pei-Yu , Hu Siou-Lian , Hsu Tsung-I
Published: August 2024

Introduction

Glioblastoma (GBM) poses a significant challenge in oncology, with median survival times barely extending beyond a year due to resistance to standard therapies like temozolomide (TMZ). This study introduces a novel therapeutic strategy combining progesterone (Prog) and abiraterone (Abi) aimed at enhancing GBM treatment efficacy by modulating the tumor microenvironment and augmenting NK cell-mediated immunity.

Methods

We employed in vitro and in vivo GBM models to assess the effects of Prog and Abi on cell viability, proliferation, apoptosis, and the immune microenvironment. Techniques included cell viability assays, Glo-caspase 3/7 apoptosis assays, RNA-seq and qPCR for gene expression, Seahorse analysis for mitochondrial function, HPLC-MS for metabolomics analysis, and immune analysis by flow cytometry to quantify NK cell infiltration.

Results

Prog significantly reduced the IC50 of Abi in TMZ-resistant GBM cell, suggesting the enhanced cytotoxicity. Treatment induced greater apoptosis than either agent alone, suppressed tumor growth, and prolonged survival in mouse models. Notably, there was an increase in CD3−/CD19−/CD56+/NK1.1+ NK cell infiltration in treated tumors, indicating a shift towards an anti-tumor immune microenvironment. The combination therapy also resulted in a reduction of MGMT expression and a suppression of mitochondrial respiration and glycolysis in GBM cells.

Conclusion

The combination of Prog and Abi represents a promising therapeutic approach for GBM, showing potential in suppressing tumor growth, extending survival, and modulating the immune microenvironment. These findings warrant further exploration into the clinical applicability of this strategy to improve outcomes for GBM patients.
First detection of V410L kdr mutation in Aedes aegypti populations of Argentina supported by toxicological evidence
Authors: Gonzalez Paula V. , Loureiro Aline C. , Gómez-Bravo Andrea , Castillo Paola , Espinosa Manuel , Gil José F. , Martins Ademir J. , Harburguer Laura V.
Published: August 2024

Background

Aedes aegypti (L.) is the main vector of dengue, yellow fever, Zika, and chikungunya viruses in many parts of the world, impacting millions of people worldwide each year. Insecticide-based interventions have been effective in controlling Aedes mosquito populations for several years, but in recent times, resistance to these compounds has developed, posing a global threat to the control of this mosquito.

Methods

Ovitraps were used to collect A. aegypti eggs in the cities of Tartagal and San Ramón de la Nueva Orán (Salta), Puerto Iguazú (Misiones), and Clorinda (Formosa). World Health Organization (WHO)-impregnated papers with the discriminating concentration (DC) of permethrin, 5X, 10X and pirimiphos methyl were used for the toxicological bioassays. We also genotyped each sample for the three kdr single nucleotide polymorphisms (SNP): V410L, V1016I, and F1534C in individual TaqMan quantitative PCR (qPCR) reactions.

Results

All investigated A. aegypti populations were highly resistant to permethrin, as the mortality percentage with the permethrin 10×DC remained below 98%. However, all populations were 100% susceptible to pirimiphos-methyl. Kdr genotyping demonstrated the presence of the V410L mutation for the first time in Argentina in all the populations studied. A prevalence of the triple mutant genotype (LL + II + CC) was observed in the northeastern cities of Clorinda (83.3%) and Puerto Iguazú (55.6%).

Conclusions

This study demonstrates for the first time the presence and intensity of resistance to permethrin in different populations from Argentina, and correlates the observed phenotype with the presence of kdr mutations (genotype).

Graphical Abstract
Gene regulatory networks reveal sex difference in lung adenocarcinoma
Authors: Saha Enakshi , Ben Guebila Marouen , Fanfani Viola , Fischer Jonas , Shutta Katherine H. , Mandros Panagiotis , DeMeo Dawn L. , Quackenbush John , Lopes-Ramos Camila M.
Published: August 2024

Background

Lung adenocarcinoma (LUAD) has been observed to have significant sex differences in incidence, prognosis, and response to therapy. However, the molecular mechanisms responsible for these disparities have not been investigated extensively.

Methods

Sample-specific gene regulatory network methods were used to analyze RNA sequencing data from non-cancerous human lung samples from The Genotype Tissue Expression Project (GTEx) and lung adenocarcinoma primary tumor samples from The Cancer Genome Atlas (TCGA); results were validated on independent data.

Results

We found that genes associated with key biological pathways including cell proliferation, immune response and drug metabolism are differentially regulated between males and females in both healthy lung tissue and tumor, and that these regulatory differences are further perturbed by tobacco smoking. We also discovered significant sex bias in transcription factor targeting patterns of clinically actionable oncogenes and tumor suppressor genes, including AKT2 and KRAS. Using differentially regulated genes between healthy and tumor samples in conjunction with a drug repurposing tool, we identified several small-molecule drugs that might have sex-biased efficacy as cancer therapeutics and further validated this observation using an independent cell line database.

Conclusions

These findings underscore the importance of including sex as a biological variable and considering gene regulatory processes in developing strategies for disease prevention and management.

Graphical Abstract
Public involvement in an aggregate and individual participant data meta-analysis of mindfulness-based programmes for mental health promotion
Authors: Friedrich Claire , Fairbairn Toni , Denton Graham , Geddes Mary , Thomas-Carr Darren , Jones Peter B. , Galante Julieta
Published: August 2024

Background

Involving the public in evidence synthesis research is challenging due to the highly analytic nature of the projects, so it is important that involvement processes are documented, reflected upon, and shared to devise best practices. There is a literature gap on the involvement of the public in individual participant data meta-analyses, particularly in public health projects. We aimed to document and reflect on our collective experiences of involving and being involved as public stakeholders at all stages of a systematic review and individual participant data meta-analysis project.

Methods

We formed a stakeholder group made of four members of the public at the beginning of our evidence synthesis project comprising a systematic review, an aggregate data meta-analysis, and an individual participant data meta-analysis of mindfulness-based programmes for mental health promotion in non-clinical adults. Following each group meeting, members and participating researchers completed written reflections; one group member collected and collated these. At the end of the project, a reflective writing workshop was held before all members completed their final reflections. Everyone completed an adapted, open-ended questionnaire which asked about what did and did not work well, the overall experience, what could be improved, and the felt impact the stakeholder group had on the research.

Results

Overall, the stakeholders and researchers reported a positive experience of working together. Positives from the stakeholders’ point of view included learning new skills, experiencing research, and making new friends. For the researchers, stakeholders helped them focus on what matters to the public and were reinvigorating research partners. The challenges stakeholders experienced included having long gaps between meetings and feeling overwhelmed. The researchers found it challenging to strike the balance between asking stakeholders to be involved and for them to learn research-related skills without overburdening them and making sure that the learning was engaging. When looking back at their experience, stakeholders described seeing their impact on the project in hindsight but that this was not felt while the project was being carried out.

Conclusion

Successfully involving the public in complex evidence synthesis projects is possible and valuable from the points of view of the researchers and the stakeholders. However, it requires a significant time, skill, and resource investment that needs to be factored in from project inception. Further guidance and stakeholder training materials would be helpful. Specific suggestions are provided.
Measurable therapeutic antibody in serum as potential predictive factor of response to anti-CD38 therapy in non-IgG-k myeloma patients
Authors: Gigliotta Emilia , Plano Federica , Corsale Giusy , Corsale Anna Maria , Aquilina Cristina , Speciale Maria , Rizzuto Andrea , Martino Enrica Antonia , Leotta Dario , Solimando Antonio Giovanni , Ria Roberto , Gentile Massimo , Siragusa Sergio , Botta Cirino
Published: August 2024

Multiple myeloma (MM) is a hematologic malignancy characterized by abnormal plasma cell proliferation in the bone marrow. Recent advancements in anti-CD38 monoclonal antibody therapies, such as daratumumab and isatuximab, have significantly improved MM patient survival. However, the lack of predictive factors of response to these therapies remains a challenge. Notably, anti-CD38 antibodies can interfere with laboratory tests, complicating response assessment. We conducted a retrospective study to evaluate the association between the appearance of positive IgGk (therapeutic antibody) on immunofixation/immunosubtraction (IF) and clinical parameters in 87 non-IgGk MM patients treated with anti-CD38 therapy. Positive IgGk IF was observed in 42 patients after a median of three treatment courses. Patients with positive IgGk IF had higher rates of complete/very good partial responses (p = 0.03) and improved progression-free survival (median not reached vs. 21.83 months, p < 0.01). High BMI (p = 0.03), higher hemoglobin (p = 0.02), lower CRP (p = 0.04), and lower monoclonal protein levels (p = 0.03) were associated with positive IgGk IF. Our findings suggest that monitoring therapeutic antibody appearance on IF may predict and optimize anti-CD38 therapy in MM. Potential explanations include the impact of patient factors (e.g. BMI) on drug pharmacokinetics, the relationship between antibody levels and immune response, and the influence of tumor biology. Further research is needed to elucidate the underlying mechanisms and clinical utility of this biomarker. Nonetheless, our results highlight the importance of considering therapeutic antibody detection when interpreting laboratory tests and managing MM patients receiving anti-CD38 therapies.
Engineering a dysbiotic biofilm model for testing root caries interventions through microbial modulation
Authors: Dame‐Teixeira Naile , El-Gendy Reem , de Oliveira Andressa Souza , Holanda Cleonice Andrade , Romeiro Luiz Antonio Soares , Do Thuy
Published: August 2024

Background

This study aimed to engineer and optimise a dysbiotic biofilm model to develop in vitro root caries for investigating microbial modulation strategies. The model involved growing complex biofilms from a saliva inoculum collected from four volunteers using two strategies. In the first strategy (“pre-treatment strategy”), bovine root slabs were used, and two natural compounds were incorporated at time 0 of the 10-day biofilm experiment, which included sucrose cycles mimicking the cariogenic environment. In the second strategy (“post-treatment strategy”), mature biofilms were grown in a modified Calgary biofilm device coated with collagen and hydroxyapatite for 7 days and then were exposed to the same natural compounds. The metatranscriptome of each biofilm was then determined and analysed. Collagenase activity was examined, and the biofilms and dentine were imaged using confocal and scanning electron microscopy (SEM). Mineral loss and lesion formation were confirmed through micro-computed tomography (μ-CT).

Results

The pH confirmed the cariogenic condition. In the metatranscriptome, we achieved a biofilm compositional complexity, showing a great diversity of the metabolically active microbiome in both pre- and post-treatment strategies, including reads mapped to microorganisms other than bacteria, such as archaea and viruses. Carbohydrate esterases had increased expression in the post-treated biofilms and in samples without sugar cycles, while glucosyltransferases were highly expressed in the presence of sucrose cycles. Enrichment for functions related to nitrogen compound metabolism and organic cyclic component metabolism in groups without sucrose compared to the sucrose-treated group. Pre-treatment of the roots with cranberry reduced microbial viability and gelatinase (but not collagenase) activity (p < 0.05). SEM images showed the complexity of biofilms was maintained, with a thick extracellular polysaccharides layer.

Conclusions

This root caries model was optimized to produce complex cariogenic biofilms and root caries-like lesions, and could be used to test microbial modulation in vitro. Pre-treatments before biofilm development and cariogenic challenges were more effective than post-treatments. The clinical significance lies in the potential to apply the findings to develop varnish products for post-professional tooth prophylaxis, aiming at implementing a strategy for dysbiosis reversal in translational research.
Efficacy of BRAF/MEK-inhibitor therapy for epithelioid glioblastoma with a novel BRAFV600 mutation
Authors: Steininger J. , Buszello C. , Oertel R. , Meinhardt M. , Schmid S. , Engellandt K. , Herold S. , Stasik S. , Ebrahimi A. , Renner B. , Thiede C. , Eyüpoglu I.Y. , Schackert G. , Beissert S. , Meier F. , Radke J. , Westphal D. , Juratli T. A.
Published: August 2024

Epithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease. Histopathology identified a highly necrotising, epithelioid-type tumour with high cell density, most compatible with the diagnosis of an eGB. DNA analysis revealed an unprecedented B-Raf protooncogene, serine/threonine kinase (BRAF) gene variant in exon 15 (ENST00000288602.6, c.1799_1810delinsATG, p.(V600_W604delinsDG)), triggering activation of the mitogen-activated protein kinase (MAPK) pathway. Consequently, we initiated MAPK inhibitor (MAPKi) therapy, utilizing a combination of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. Liquid chromatography–tandem mass spectrometry analysis confirmed the drugs’ presence in the patient’s cerebrospinal fluid, indicating their capacity to cross the blood-brain barrier. Remarkably, the patient responded very well to therapy and transitioned from a near-comatose state to significantly improved health, sustained for over three months. This study highlights that MAPKi, particularly targeted towards novel BRAFV600 mutations, might offer promising advancements in eGB treatment strategies.