bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutant p53 murine oviductal epithelial cells induce progression of high-grade serous carcinoma and are most sensitive to simvastatin therapy in vitro and in vivo
Authors: Pereira Madison , Glogova Alice , Haagsma Jacob , Stewart Julia , Shepherd Trevor G. , Petrik Jim 
Published: November 2023

AbstractHigh-grade serous carcinoma (HGSC) is the most common and aggressive subtype of epithelial ovarian cancer, characterized by gain-of-function TP53 mutations originating in the fallopian tube epithelium. Therapeutic intervention occurs at advanced metastatic disease, due to challenges in early-stage diagnosis, with common disease recurrence and therapy resistance despite initial therapy success. The mevalonate pathway is exploited by many cancers and is potently inhibited by statin drugs. Statins have shown anti-cancer activity in many, but not all cancers. Here, we investigated the role of p53 status in relation to mevalonate pathway signaling in murine oviductal epithelial (OVE) cells and identified OVE cell sensitivity to statin inhibition. We found that p53R175H mutant and Trp53 knockout OVE cells have increased mevalonate pathway signaling compared to p53 wild-type OVE cells. Through orthotopic implantation to replicate the fallopian tube origin of HGSC, p53R175H mutant cells upregulated the mevalonate pathway to drive progression to advanced-stage ovarian cancer, and simvastatin treatment abrogated this effect. Additionally, simvastatin was more efficacious at inhibiting cell metabolic activity in OVE cells than atorvastatin, rosuvastatin and pravastatin. In vitro, simvastatin demonstrated potent effects on cell proliferation, apoptosis, invasion and migration in OVE cells regardless of p53 status. In vivo, simvastatin induced ovarian cancer disease regression through decreased primary ovarian tumor weight and increased apoptosis. Simvastatin also significantly increased cytoplasmic localization of HMG-CoA reductase in ovarian tumors. Downstream of the mevalonate pathway, simvastatin had no effect on YAP or small GTPase activity. This study suggests that simvastatin can induce anti-tumor effects and could be an important inhibitor of ovarian cancer progression.
Pharmacokinetic and pharmacodynamic considerations for antifungal therapy optimisation in the treatment of intra-abdominal candidiasis
Authors: Novy Emmanuel , Roger Claire , Roberts Jason A. , Cotta Menino Osbert 
Published: November 2023

AbstractIntra-abdominal candidiasis (IAC) is one of the most common of invasive candidiasis observed in critically ill patients. It is associated with high mortality, with up to 50% of deaths attributable to delays in source control and/or the introduction of antifungal therapy. Currently, there is no comprehensive guidance on optimising antifungal dosing in the treatment of IAC among the critically ill. However, this form of abdominal sepsis presents specific pharmacokinetic (PK) alterations and pharmacodynamic (PD) challenges that risk suboptimal antifungal exposure at the site of infection in critically ill patients. This review aims to describe the peculiarities of IAC from both PK and PD perspectives, advocating an individualized approach to antifungal dosing. Additionally, all current PK/PD studies relating to IAC are reviewed in terms of strength and limitations, so that core elements for the basis of future research can be provided.
De novo biosynthesis of 2-hydroxyterephthalic acid, the monomer for high-performance hydroxyl modified PBO fiber, by enzymatic Kolbe–Schmitt reaction with CO2 fixation
Authors: Zhou Yali , Zhang Shiding , Huang Shiming , Fan Xuanhe , Su Haijia , Tan Tianwei 
Published: November 2023

Abstract
Background
High-performance poly(p-phenylenebenzobisoxazole) (PBO) fiber, with excellent mechanical properties (stiffness, strength, and toughness), high thermal stability combined and light weight, are widely employed in automotive and aerospace composites, body armor and sports goods. Hydroxyl modified PBO (HPBO) fiber shows better photostability and interfacial shear strength. 2-Hydroxyterephthalic acid (2-HTA), the monomer for the HPBO fiber, is usually synthesized by chemical method, which has poor space selectivity and high energy consumption. The enzymatic Kolbe–Schmitt reaction, which carboxylates phenolic substrates to generate hydroxybenzoic acids with bicarbonate/CO2, was applied in de novo biosynthesis of 2-HTA with CO2 fixation.

Results
The biosynthesis of 2-HTA was achieved by the innovative application of hydroxybenzoic acid (de)carboxylases to carboxylation of 3-hydroxybenzoic acid (3-HBA) at the para-position of the benzene carboxyl group, known as enzymatic Kolbe–Schmitt reaction. 2,3-Dihydroxybenzoic acid decarboxylase from Aspergillus oryzae (2,3-DHBD_Ao) were expressed in recombinant E. coli and showed highest activity. The yield of 2-HTA was 108.97 ± 2.21 μg/L/mg protein in the whole-cell catalysis. In addition, two amino acid substitutions, F27G and T62A, proved to be of great help in improving 2,3-DHBD activity. The double site mutation F27G/T62A increased the production of 2-HTA in the whole-cell catalysis by 24.7-fold, reaching 2.69 ± 0.029 mg/L/mg protein. Moreover, de novo biosynthetic pathway of 2-HTA was constructed by co-expression of 2,3-DHBD_Ao and 3-hydroxybenzoate synthase Hyg5 in S. cerevisiae S288C with Ura3, Aro7 and Trp3 knockout. The engineered strain synthesized 45.40 ± 0.28 μg/L 2-HTA at 36 h in the CO2 environment.

Conclusions
De novo synthesis of 2-HTA has been achieved, using glucose as a raw material to generate shikimic acid, chorismic acid, and 3-HBA, and finally 2-HTA. We demonstrate the strong potential of hydroxybenzoate (de)carboxylase to produce terephthalic acid and its derivatives with CO2 fixation.
“Whenever I tell her to wear slippers, she turns a deaf ear. She never listens”: a qualitative descriptive research on the barriers to basic lymphedema management and quality of life in lymphatic filariasis patients in a rural block of eastern India
Authors: Kumar Pragya , Ahmad Shamshad , Bhar Ditipriya , Roy Ria , Singh Bhavna 
Published: November 2023

Abstract
Background
Chronic lymphatic filariasis patients in Bihar, India, need management of lymphedema to live a disability-free life. For patients who have recurrent attacks of acute dermato-lymphangio-adenitis (ADLA), World Health Organization (WHO) has recommended simple home-based measures that include maintaining hygiene, skin care, and limb movement. However, patients in rural areas are unable to adopt them, resulting in a vicious cycle of ADLA attacks. There might be multiple realities from patients’ and healthcare workers’ perspectives that were unexplored. Qualitative research was deemed best suitable to identify the barriers to carrying out home-based lymphedema practices that adversely affected quality of life.

Methods
The qualitative descriptive study was conducted in two villages in the rural field practice area under a tertiary care hospital in Bihar. Researchers purposively selected ten participants, including patients affected by lymphedema, their caregivers, the grassroots healthcare workers, and the block health manager. In-depth interviews were conducted using a semi-structured interview guide. Data were entered into QDA Miner Lite, where researchers did attribute, in-vivo, process, descriptive, emotion, and holistic coding, followed by content analysis, where categories and themes emerged from the codes.

Results
Three themes emerged: the inherent nature of disease, patient-related factors, and healthcare system-related factors. The fifteen identified barriers were low awareness, low adherence, low health-seeking behavior, poor personal hygiene, and categories like signs and symptoms, seasonal factors, hampered activities of daily living, hopelessness from not getting cured, psychosocial difficulty, lack of capacity building and receipt of incentives by healthcare workers, unavailability of laboratory diagnosis and management of complications at the facility, inconsistent drug supply, and no financial assistance.

Conclusions
Accessibility to WaSH, regular training of home-based care, increasing the capacity and motivation of grassroots workers, and the generation of in-depth awareness among the patients are required to achieve the elimination of filariasis, with MMDP as a key component of that strategy for endemic districts across the whole country.

Graphical Abstract
Prevalence and predictors of sustained remission/low disease activity after discontinuation of induction or maintenance treatment with tumor necrosis factor inhibitors in rheumatoid arthritis: a systematic and scoping review
Authors: Ward Michael M. , Madanchi Nima , Yazdanyar Ali , Shah Nehal R. , Constantinescu Florina 
Published: November 2023

Abstract
Background
To determine the prevalence of sustained remission/low disease activity (LDA) in patients with rheumatoid arthritis (RA) after discontinuation of tumor necrosis factor inhibitors (TNFi), separately in induction treatment and maintenance treatment studies, and to identify predictors of successful discontinuation.

Methods
We performed a systematic literature review of studies published from 2005 to May 2022 that reported outcomes after TNFi discontinuation among patients in remission/LDA. We computed prevalences of successful discontinuation by induction or maintenance treatment, remission criterion, and follow-up time. We performed a scoping review of predictors of successful discontinuation.

Results
Twenty-two induction-withdrawal studies were identified. In pooled analyses, 58% (95% confidence interval (CI) 45, 70) had DAS28 < 3.2 (9 studies), 52% (95% CI 35, 69) had DAS28 < 2.6 (9 studies), and 40% (95% CI 18, 64) had SDAI ≤ 3.3 (4 studies) at 37–52 weeks after discontinuation. Among patients who continued TNFi, 62 to 85% maintained remission. Twenty-two studies of maintenance treatment discontinuation were also identified. At 37–52 weeks after TNFi discontinuation, 48% (95% CI 38, 59) had DAS28 < 3.2 (10 studies), and 47% (95% CI 33, 62) had DAS28 < 2.6 (6 studies). Heterogeneity among studies was high. Data on predictors in induction-withdrawal studies were limited. In both treatment scenarios, longer duration of RA was most consistently associated with less successful discontinuation.

Conclusions
Approximately one-half of patients with RA remain in remission/LDA for up to 1 year after TNFi discontinuation, with slightly higher proportions in induction-withdrawal settings than with maintenance treatment discontinuation.
Pleomorphic liposarcoma of the extremity with solitary huge liver metastasis at initial diagnosis treated with conversion surgery combined with adjuvant chemotherapy: a case report
Authors: Shimomura Seiji , Shirai Toshiharu , Terauchi Ryu , Mizoshiri Naoki , Mori Yuki , Inuma Kanako , Tsuchida Shinji , Morimura Ryo , Ikoma Hisashi , Takahashi Kenji 
Published: November 2023

Abstract
Background
Pleomorphic liposarcoma is the rarest subtype of liposarcoma. Pleomorphic liposarcomas are generally unresponsive to chemotherapy and radiotherapy. Moreover, metastasis in the liver, as the first and sole site, from a primary extremity soft tissue sarcoma, including pleomorphic liposarcoma, is extremely rare. Information regarding the appropriate management of these lesions is limited.

Case presentation
A 50-year-old Japanese woman presented with a mass in the left thigh. Imaging examination revealed a soft tissue sarcoma on the left posterior thigh. The tumor was histologically diagnosed as pleomorphic liposarcoma. Computed tomography examination for assessment of metastases incidentally detected a huge liver mass. Wide excision of sarcoma was performed prior to chemotherapy. Right trisectionectomy was necessary to achieve hepatic clearance; however, the future liver remnant volume was insufficient. Therefore, we decided to administer anthracycline-based chemotheraphy to shrink the tumor. After seven courses of adriamycin-based chemotherapy, the liver tumor size was reduced from 211 mm × 106 mm × 180 mm to 105 mm × 66 mm × 90 mm. Finally, a right hemihepatectomy was performed. The patient was continuously monitored and was metastasis or local recurrence free within 5 months after liver surgery.

Conclusion
Chemotherapy is effective in some cases for the treatment of unresectable liver metastases of pleomorphic liposarcoma, and complete resection is possible with conversion surgery. If the patient’s general condition permits, anthracycline-based chemotherapy can be used for the treatment of stage 4 pleomorphic liposarcoma.
Development of [89Zr]Zr-hCD103.Fab01A and [68Ga]Ga-hCD103.Fab01A for PET imaging to noninvasively assess cancer reactive T cell infiltration: Fab-based CD103 immunoPET
Authors: Fan Xiaoyu , Ważyńska Marta A. , Kol Arjan , Perujo Holland Noemi , Fernandes Bruna , van Duijnhoven Sander M. J. , Plat Annechien , van Eenennaam Hans , Elsinga Philip H. , Nijman Hans W. , de Bruyn Marco 
Published: November 2023

Abstract
Background
CD103 is an integrin specifically expressed on the surface of cancer-reactive T cells. The number of CD103+ T cells significantly increases during successful immunotherapy and might therefore be an attractive biomarker for noninvasive PET imaging of immunotherapy response. Since the long half-life of antibodies preclude repeat imaging of CD103+ T cell dynamics early in therapy, we therefore here explored PET imaging with CD103 Fab fragments radiolabeled with a longer (89Zr) and shorter-lived radionuclide (68Ga).

Methods
Antihuman CD103 Fab fragment Fab01A was radiolabeled with 89Zr or 68Ga, generating [89Zr]Zr-hCD103.Fab01A and [68Ga]Ga-hCD103.Fab01A, respectively. In vivo evaluation of these tracers was performed in male nude mice (BALB/cOlaHsd-Foxn1nu) with established CD103-expressing CHO (CHO.CD103) or CHO-wildtype (CHO.K1) xenografts, followed by serial PET imaging and ex vivo bio-distribution.

Results
[89Zr]Zr-hCD103.Fab01A showed high tracer uptake in CD103+ xenografts as early as 3 h post-injection. However, the background signal remained high in the 3- and 6-h scans. The background was relatively low at 24 h after injection with sufficient tumor uptake. [68Ga]Ga-hCD103.Fab01Ashowed acceptable uptake and signal-to-noise ratio in CD103+ xenografts after 3 h, which decreased at subsequent time points.

Conclusion
[89Zr]Zr-hCD103.Fab01A demonstrated a relatively low background and high xenograft uptake in scans as early as 6 h post-injection and could be explored for repeat imaging during immunotherapy in clinical trials. 18F or 64Cu could be explored as alternative to 68Ga in optimizing half-life and radiation burden of the tracer.
Estimation of aboveground biomass and carbon stocks of Quercus ilex L. saplings using UAV-derived RGB imagery
Authors: Juan-Ovejero R. , Elghouat A. , Navarro C. J. , Reyes-Martín M. P. , Jiménez M. N. , Navarro F. B. , Alcaraz-Segura D. , Castro J. 
Published: November 2023

Abstract
Key message
Crown area, sapling height, and biovolume extracted from UAV-acquired RGB images provided accurate estimates of aboveground biomass and carbon stocks in a 5-year-old holm oak (Quercus ilex L.) plantation. Our models regressing UAV-derived sapling variables against ground-based measurements exhibited high R2 values (0.78–0.89), thereby reflecting that RGB data can be used as an effective tool for measuring young individuals.

Context
The monitoring of tree sapling performance from the early stages of reforestation is of particular importance in the context of the global efforts to restore forests. Yet, most models to estimate carbon sequestration are developed for adult trees. Thus, the few models specifically developed for young trees rely on ground-based field sampling of tree growth parameters, which is time-consuming and difficult to implement at large spatial scales.

Aims
Our objectives were as follows: (1) to study the potential of UAV-based RGB imagery to detect and extract sapling variables (e.g., crown area, height, and biovolume) by comparing ground-based sapling measurements with UAV-derived data and (2) to compare the accuracy of the data estimated from RGB imagery with existing traditional field-based allometric equations.

Methods
We used a 5-year-old holm oak (Quercus ilex L. subsp. ballota (Desf.) Samp.) plantation (N = 617 plants), and their crown area, height, and biovolume were estimated from RGB imagery. Subsequently, the plants were harvested and the UAV-derived data were compared with field-measured sapling height and aboveground biomass values. Carbon content in leaves and stems was measured in a subsample of the saplings to estimate carbon stocks.

Results
The models fitted with UAV-derived variables displayed high performance, with R2 values from 0.78 to 0.89 for height, leaf and stem biomass, total aboveground biomass, and carbon stocks. Moreover, aboveground biomass outputs calculated with field height and UAV-derived height using allometric equations exhibited R2 values from 0.65 to 0.68.

Conclusions
Given the affordable cost of RGB cameras and the versatility of drones, we suggest that UAV-based models may be a cost-effective method to estimate the biomass and carbon stocks of young plantations. However, further studies conducting drone flights in different conditions are needed to make this approach more scalable.
Stability analysis for set-valued inverse mixed variational inequalities in reflexive Banach spaces
Authors: Qu Xiaolin , Li Wei , Xing Chenkai , Luo Xueping 
Published: November 2023

AbstractThis work is devoted to the analysis for a new class of set-valued inverse mixed variational inequalities (SIMVIs) in reflexive Banach spaces, when both the mapping and the constraint set are perturbed simultaneously by two parameters. Several equivalence characterizations are given for SIMVIs to have nonempty and bounded solution sets. Based on the equivalence conditions, under the premise of monotone mappings, the stability result for the SIMVIs is obtained in the reflexive Banach space. Furthermore, to illustrate the results, an example of the traffic network equilibrium control problem is provided at the end of this paper. The results presented in this paper generalize and extend some known results in this area.
Community evaluation of the physical and insecticidal durability of DuraNet® Plus, an alpha-cypermethrin and piperonyl butoxide incorporated mosquito net: protocol for a multi-country study in West, Central and East Africa
Authors: Agbevo Abel , Ahogni Idelphonse , Menze Benjamin , Tungu Patrick , Kemibala Elison E. , Govoetchan Renaud , Wondji Charles , Padonou Germain Gil , Ngufor Corine 
Published: November 2023

Abstract
Background
Pyrethroid-PBO nets have demonstrated improved impact against clinical malaria transmitted by pyrethroid resistant mosquito vectors and are being scaled up across Africa. However very little is known about their physical and insecticidal durability under operational conditions. This study will investigate the attrition, fabric integrity, insecticide content and bioefficacy of DuraNet® Plus, a new WHO prequalified alphacypermethrin and PBO incorporated net developed by Shobikaa Impex Private Limited over 3 years of field use in communities in Benin, Cameroon and Tanzania.

Methods
The study will be conducted in parallel in selected villages in Zakpota District in Benin, Mbalmayo, District in Cameroon and Muheza District in Tanzania. In each country, ~ 1800 households will be recruited and randomised to receive DuraNet® Plus or DuraNet® (a WHO prequalified alphacypermethrin-only ITN). Follow up surveys will be performed at 1 month post distribution to investigate adverse events and subsequently every 6–12 months to assess ITN attrition and fabric integrity following standard WHO procedures. A second cohort of nets will be withdrawn every 6–12 months and assessed for alpha-cypermethrin and PBO content and for entomological activity in laboratory bioassays (cone bioassays and tunnel tests). Alpha-cypermethrin bioefficacy will be monitored using the susceptible Anopheles gambiae Kisumu strain in cone bioassays while PBO bioefficacy will be monitored using pyrethroid resistant strains with overexpressed P450 enzymes in tunnel tests to determine the proportion of efficacious nets (≥ 95% knockdown, ≥ 80% mortality or ≥ 90% blood feeding inhibition in tunnels) at each time point. Nets withdrawn at 12, 24 and 36 months from each country will also be tested in experimental hut trials against wild free-flying pyrethroid resistant Anopheles gambiae sl in Côvè Benin to investigate the superiority of DuraNet® Plus over DuraNet® at each time point under semi field conditions.

Conclusion
This large-scale multi country trial will provide useful information on the durability of a pyrethroid-PBO net (DuraNet® Plus) in 3 different regions in sub-Saharan Africa. The methods proposed for bioefficacy testing could also contribute towards the development of new standardised guidelines for monitoring the insecticidal efficacy of pyrethroid-PBO nets under operational conditions.
Treating patients with geographic atrophy: are we there yet?
Authors: Antonio-Aguirre Bani , Arevalo J. Fernando 
Published: November 2023

AbstractGeographic atrophy (GA) is a progressive degenerative disease that significantly contributes to visual impairment in individuals aged 50 years and older. The development of GA is influenced by various modifiable and non-modifiable risk factors, including age, smoking, and specific genetic variants, particularly those related to the complement system regulators. Given the multifactorial and complex nature of GA, several treatment approaches have been explored, such as complement inhibition, gene therapy, and cell therapy. The recent approval by the Food and Drug Administration of pegcetacoplan, a complement C3 inhibitor, marks a significant breakthrough as the first approved treatment for GA. Furthermore, numerous interventions are currently in phase II or III trials, alongside this groundbreaking development. In light of these advancements, this review provides a comprehensive overview of GA, encompassing risk factors, prevalence, genetic associations, and imaging characteristics. Additionally, it delves into the current landscape of GA treatment, emphasizing the latest progress and future considerations. The goal of starting this discussion is to ultimately identify the most suitable candidates for each therapy, highlight the importance of tailoring treatments to individual cases, and continue monitoring the long-term implications of these emerging interventions.