bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut Microbiome Mediates Ferroptosis Resistance for Colorectal Cancer Development
Authors: Zhang Ruoxi , Kang Rui , Tang Daolin 
Published: January 2024

Abstract
Colorectal cancer is a prevalent cancer type in the United States, affecting both genders and influenced by genetics and environmental factors. The role of the gut microbiome in colorectal cancer development and therapy response is a burgeoning field of study. A recent study uncovered that trans-3-indoleacrylic acid (IDA), a microbial metabolite from P. anaerobius, promotes colorectal cancer by inhibiting ferroptosis, a type of nonapoptotic cell death driven by unrestricted lipid peroxidation and subsequent membrane damage. IDA activates aryl hydrocarbon receptor (AHR), a nuclear transcription factor, leading to the expression of aldehyde dehydrogenase 1 family member A3 (ALDH1A3). ALDH1A3, known for aldehyde detoxification, also contributes to ferroptosis resistance by generating reduced nicotinamide adenine dinucleotide (NADH), critical for the synthesis of reduced coenzyme Q10 (COQH10), by apoptosis-inducing factor mitochondria-associated 2 (AIFM2, also known as FSP1). Knocking out AHR, AIFM2, or ALDH1A3 reverses the inhibitory effect of IDA on ferroptosis and IDA-mediated tumor growth. Significantly, P. anaerobius is enriched in patients with colorectal cancer, and supplementing IDA or P. anaerobius accelerates colorectal cancer progression in spontaneous or orthotopic mouse models. Taken together, these findings suggest that targeting P. anaerobius–mediated ferroptosis resistance emerges as a promising strategy to combat colorectal cancer development.
Development of a [89Zr]Zr-labeled Human Antibody using a Novel Phage-displayed Human scFv Library
Authors: Singh Abhay K. , Lewis Calvin D. , Boas Cristian A.W.V. , Diebolder Philipp , Jethva Prashant N. , Rhee Aaron , Song Jong Hee , Goo Young Ah , Li Shunqian , Nickels Michael L. , Liu Yongjian , Rogers Buck E. , Kapoor Vaishali , Hallahan Dennis E. 
Published: January 2024

Abstract

Purpose:
Tax-interacting protein 1 (TIP1) is a cancer-specific radiation-inducible cell surface antigen that plays a role in cancer progression and resistance to therapy. This study aimed to develop a novel anti-TIP1 human antibody for noninvasive PET imaging in patients with cancer.

Experimental Design:
A phage-displayed single-chain variable fragment (scFv) library was created from healthy donors’ blood. High-affinity anti-TIP1 scFvs were selected from the library and engineered to human IgG1. Purified Abs were characterized by size exclusion chromatography high-performance liquid chromatography (SEC-HPLC), native mass spectrometry (native MS), ELISA, BIAcore, and flow cytometry. The labeling of positron emitter [89Zr]Zr to the lead Ab, L111, was optimized using deferoxamine (DFO) chelator. The stability of [89Zr]Zr-DFO-L111 was assessed in human serum. Small animal PET studies were performed in lung cancer tumor models (A549 and H460).

Results:
We obtained 95% pure L111 by SEC-HPLC. Native MS confirmed the intact mass and glycosylation pattern of L111. Conjugation of three molar equivalents of DFO led to the optimal DFO-to-L111 ratio of 1.05. Radiochemical purity of 99.9% and specific activity of 0.37 MBq/μg was obtained for [89Zr]Zr-DFO-L111. [89Zr]Zr-DFO-L111 was stable in human serum over 7 days. The immunoreactive fraction in cell surface binding studies was 96%. In PET, preinjection with 4 mg/kg cold L111 before [89Zr]Zr-DFO-L111 (7.4 MBq; 20 μg) significantly (P &lt; 0.01) enhanced the tumor-to-muscle standard uptake values (SUVmax) ratios on day 5 compared with day 2 postinjection.

Conclusions:
L111 Ab targets lung cancer cells in vitro and in vivo. [89Zr]Zr-DFO-L111 is a human antibody that will be evaluated in the first in-human study of safety and PET imaging.
Real-world Trends, Rural-urban Differences, and Socioeconomic Disparities in Utilization of Narrow versus Broad Next-generation Sequencing Panels
Authors: Zhao Yiqing , Dimou Anastasios , Fogarty Zachary C. , Jiang Jun , Liu Hongfang , Wong William B. , Wang Chen 
Published: January 2024

Abstract

Advances in genetic technology have led to the increasing use of genomic panels in precision oncology practice, with panels ranging from a couple to hundreds of genes. However, the clinical utilization and utility of oncology genomic panels, especially among vulnerable populations, is unclear. We examined the association of panel size with socioeconomic status and clinical trial matching. We retrospectively identified 9,886 eligible adult subjects in the Mayo Clinic Health System who underwent genomic testing between January 1, 2016 and June 30, 2020. Patient data were retrieved from structured and unstructured data sources of institutional collections, including cancer registries, clinical data warehouses, and clinical notes. Socioeconomic surrogates were approximated using the Area Deprivation Index (ADI) corresponding to primary residence addresses. Logistic regression was performed to analyze relationships between ADI or rural/urban status and (i) use of genomic test by panel size; (ii) clinical trial matching status. Compared with patients from the most affluent areas, patients had a lower odds of receiving a panel test (vs. a single-gene test) if from areas of higher socioeconomic deprivation [OR (95% confidence interval (CI): 0.71 (0.61–0.83), P &lt; 0.01] or a rural area [OR (95% CI): 0.85 (0.76–0.96), P &lt; 0.01]. Patients in areas of higher socioeconomic deprivation were less likely to be matched to clinical trials if receiving medium panel tests [(OR) (95% CI): 0.69 (0.49–0.97), P = 0.03]; however, there was no difference among patients receiving large panel tests (P &gt; 0.05) and rural patients were almost 2x greater odds of being matched if receiving a large panel test [(OR) (95% CI): 1.76 (1.21–2.55), P &lt; 0.01].

Significance:
We identified socioeconomic and rurality disparities in the use of genomic tests and trial matching by panel size, which may have implications for equal access to targeted therapies. The lack of association between large panel tests and clinical trial matching by socioeconomic status, suggests a potential health equity impact, while removing barriers in access to large panels for rural patients may improve access to trials. However, further research is needed.
Functional Heterogeneity in MET Pathway Activation in PDX Models of Osimertinib-resistant EGFR-driven Lung Cancer
Authors: Roper Nitin , El Meskini Rajaa , Maity Tapan , Atkinson Devon , Day Amanda , Pate Nathan , Cultraro Constance M. , Pack Svetlana , Zgonc Valerie , Weaver Ohler Zoe , Guha Udayan 
Published: January 2024

Abstract

MET pathway activation is one of the most common mechanisms of resistance to osimertinib in EGFR-mutant non–small cell lung cancer (NSCLC). We previously demonstrated spatial and temporal heterogeneity in MET pathway activation upon osimertinib resistance in EGFR-mutant NSCLC; however, the functional relevance of these findings is unclear. Here, we generated 19 patient-derived xenografts (PDX) from 9 patients with multi-region and temporal sampling of osimertinib-resistant tumor tissue from patients with EGFR-mutant NSCLC. MET pathway activation was a putative mechanism of osimertinib resistance in 66% (n = 6/9) patients from whom PDXs were generated. Significant spatial and temporal heterogeneity in MET pathway activation was evident. Osimertinib-resistant PDXs with MET amplification by FISH (defined as MET/CEP7 ratio ≥2.0 or mean MET ≥ 6.0 copies/cell) and high-level phospho-MET, but not c-MET expression, had better responses to osimertinib and savolitinib combination than to osimertinib alone. MET polysomy tumors by FISH from both PDXs and patients had evidence of subclonal phospho-MET expression. Select MET polysomy PDX tumors with phospho-MET expression responded better to osimertinib and savolitinib combination than MET polysomy PDX tumors without phospho-MET expression. Our results suggest osimertinib and savolitinib combination is most effective for osimertinib-resistant EGFR-mutant tumors with MET pathway activation as evidenced by phospho-MET. As subclonal MET amplification may be evident in MET polysomy tumor progression, MET polysomy warrants close clinical follow-up with phospho-MET IHC in parallel with FISH diagnostic.

Significance:
Using a novel cohort of in vivo PDX models of MET pathway activation with acquired resistance to osimertinib in EGFR-mutant lung cancer, we demonstrate that phospho-MET may be a clinically relevant assay to guide treatment selection with osimertinib and savolitinib combination. In addition, our work shows that patients with MET polysomy tumors may have subclonal MET amplification and therefore require close follow up for the use of osimertinib and savolitinib combination.
An on-chip soft-start pseudo-current hysteresis-controlled buck converter for automotive applications
Authors: Boutaghlaline Anas , El Khadiri Karim , Tahiri Ahmed 
Published: January 2024

This paper introduces a novel direct current to direct current (DC-DC) buck converter that uses a pseudo-current hysteresis controller and an on-chip soft start circuit for improved transient performance in automotive applications. The proposed converter, implemented with Taiwan semiconductor manufacturing company (TSMC) 0.18 µm complementary metal oxide semiconductor (CMOS) one-poly-six-metal (1P6M) technology, includes a rail-to-rail current detection circuit and an on-chip soft start circuit to handle transient responses and improve efficiency. Transient response analysis shows fast settling times of 28 µs for both load current changes from 100 mA to 1 A and reversals with consistent transient voltages of approximately 190 mV and peak power efficiency of 99.32% at 5 V output voltage and 100 mA load current. Additionally, the converter maintains a constant output voltage of approximately 5 V across the entire load current range with an average accuracy of 90.41%. A comparative analysis with previous work shows superior performance in terms of figure of merit (FOM). Overall, the proposed pseudo-current hysteresis controlled buck converter exhibits remarkable transient response, load regulation and power efficiency, positioning it as a promising solution for demanding applications, particularly in automotive systems where precise voltage regulation is crucial.
Field oriented control driver development based on BTS7960 for physiotherapy robot implementation
Authors: Halisyah Andi Nur , Adiputra Dimas , Al Farouq Ardiansyah 
Published: January 2024

In conjunction with sustainable development goal 3 (SDG 3), it is important to develop a national electrical component for physiotherapy robot development. This study aimed to develop an open-loop field-oriented control (FOC) driver utilizing BTS7960. The driver utilized three BTS7960s that produce sinewave with variable angular frequency (ω). The research then compared the open-loop FOC driver with electronics speed controller (ESC) performance to drive a brushless DC (BLDC) motor with an initial rotation per minute (RPM) of 400, 500, and 600. The main observation was RPM reduction when the BLDC motor was subjected to loads of 20, 35, 50, 65, and 80 gr. The result showed that the open-loop FOC driver performed better, especially on an 80 gr load. For an initial RPM of 600, the RPM reduced to 100 when controlled with an open-loop FOC driver, but lesser when controlled using ESC. The open-loop FOC driver produces higher torque on the BLDC motor so it could rotate with less reduction compared to ESC, which is evident. The open-loop FOC driver can be easily developed using BTS7960 with a settling time of 4 seconds. However future studies should still consider close-loop FOC drivers to achieve higher torque performance and faster transient response for physiotherapy robot applications.
Improved design and performance of the global rectenna system for wireless power transmission applications around 2.45 GHz
Authors: En-Naghma Walid , Halaq Hanan , El Ougli Abdelghani 
Published: January 2024

This work proposes a new conception of the global microstrip rectenna system operating around 2.45 GHz. This improved rectenna system associates a receiving antenna with a rectifier circuit. This rectenna is printed on an FR4 substrate. The proposed antenna is a 1×4 microstrip antenna patch array with pentagonal patches using the defective ground structure method and operates with circular polarization. To show the effectiveness of this array, the results obtained by the computer simulation technology microwave studio (CST MWS) software prove that this array is good in terms of high gain, high directivity, high efficiency, wideband, small volume, and well-adaptation, and all these results are confirmed by another solver high-frequency structure simulator (HFSS). The improved rectifier is a microstrip rectifier that uses an HSMS2852 Schottky diode by using a series topology. The effectiveness of this rectifier is proved by the simulation results using advanced design system (ADS) software in terms of well-matching input impedance, high efficiency, and important output direct current (DC) voltage value. The proposed rectenna system is more efficient compared with the existing works and is very appropriate for several applications of wireless power transmission to power supply electronic instruments in various fields cleanly on our planet.
Association Between Posterior Tibial Slope and ACL Injury in Pediatric Patients: A Systematic Review and Meta-analysis
Authors: Farid Alexander R. , Pradhan Pratik , Stearns Stephen A. , Kocher Mininder S. , Fabricant Peter D. 
Published: January 2024

Background: The posterior tibial slope (PTS) has been proposed to be a radiographic risk factor for anterior cruciate ligament (ACL) injury in adults. However, this has not been well established in pediatric patients. Purpose: This systematic review and meta-analysis was performed to investigate any association between PTS and ACL tears in the pediatric population. Study Design: Systematic review and meta-analysis; Level of evidence, 4. Methods: A systematic review was performed to identify studies that examined the relationship between PTS, medial tibial slope (MTS), and lateral tibial slope (LTS) and ACL tears in children and adolescents aged ≤18 years. Full-text observational studies comparing PTS, MTS, and/or LTS values between pediatric (≤18 years of age) patients with and without ACL injury were included in this analysis. Review articles and case series were excluded. The authors calculated the mean difference (MD) via a restricted maximum-likelihood estimator for tau square and a Hartung-Knapp adjustment for random-effects model. Results: A total of 348 articles were identified in the initial database search, yielding 10 for final inclusion and analysis. There was no statistically significant association between PTS (MD, 1.13°; 95% CI, –0.55° to 2.80°; P = .10), MTS (MD, 0.36°; 95% CI, –0.37° to 1.10°; P = .27), or LTS (MD, 1.41°; 95% CI, –0.20° to 3.02°; P = .075) and risk for ACL injury in this population. Conclusion: The current study found that unlike what has been shown in adult populations, increased PTS may not be a significant risk factor for ACL tears in pediatric and adolescent patents. LTS was the only measured parameter that neared statistical significance, perhaps suggesting a potential role for this measurement in determining ACL risk if further research is done in this population.
Mild obstructive sleep apnoea in females:post hocanalysis of the MERGE randomised controlled trial
Authors: Wimms Alison J. , Kelly Julia L. , Turnbull Christopher D. , McMillan Alison , Craig Sonya E. , O'Reilly John F. , Nickol Annabel H. , Decker Meredith D. , Willes Leslee A. , Calverley Peter M.A. , Benjafield Adam V. , Stradling John R. , Morrell Mary J. ,   on behalf of the MERGE Trial Investigators
Published: January 2024

BackgroundApost hocanalysis of the MERGE trial was conducted, to investigate whether sex differences are evident at the mildest end of the disease spectrum, for symptoms associated with obstructive sleep apnoea (OSA) and the response to continuous positive airway pressure (CPAP) treatment.MethodsMERGE participants with mild OSA (apnoea–hypopnoea index 5–15 events·h−1; American Academy of Sleep Medicine 2012 criteria) were randomised to either CPAP plus standard care (sleep hygiene counselling) or standard care alone for 3 months. Quality of life (QoL) was measured by questionnaires completed before and after the 3 months. Thispost hocanalysis of participants of the MERGE trial compared the symptom presentation, and response to CPAP, between the sexes.Results233 patients were included; 71 (30%) were female. Females were more symptomatic at baseline in all QoL questionnaires. Specifically, females had lower 36-item Short-Form Health Survey (SF-36) Vitality scores (mean±sd39.1±10.1versus44.8±10.3) and higher Epworth Sleepiness Scale (ESS) scores (mean±sd11.0±4.2versus9.5±4.4). Both sexes experienced snoring, but more females reported fatigue and more males reported witnessed apnoeas. All symptoms improved with CPAP for both sexes; however, females had larger improvements in SF-36 Vitality scores, which was the primary outcome of the MERGE trial (mean change 9.4 (95% CI 6.8–12.0)versus6.0 (95% CI 4.3–7.7); p=0.034), and ESS (mean change −4.1 (95% CI −5.1– −3.0)versus−2.5 (95% CI −3.1– −1.8); p=0.015), after adjustment for baseline scores and CPAP usage.ConclusionsSex differences are apparent in patients with mild OSA. Females experience worse QoL symptoms than males at presentation to the sleep clinic; however, these improve significantly with CPAP treatment.
Adjustments to maintenance therapy and the reasoning behind them among COPD outpatients in Austria: the STEP study
Authors: Vafai-Tabrizi Florian , Schwab Ulrich , Brecht Stephan , Funk Georg-Christian 
Published: January 2024

BackgroundAdjustments to COPD maintenance treatment are based on different guidelines. In Austria, there is a lack of real-world data on treatment adjustments of COPD outpatients and their underlying rationale. The STEP study characterised change patterns of pharmacological maintenance therapy in COPD outpatients in predefined categories of step-up, step-down and switch, the underlying reasons, and predictors in clinical routine in Austria.MethodsSTEP was a single-visit non-interventional study in Austria. 77 pulmonologists based in outpatient clinics documented previous and adapted COPD therapy, reason for change, patient characteristics, COPD phenotype, and lung function. Patients’ COPD symptom burden was assessed by using the COPD Assessment Test (CAT). Predictors for therapy changes were identified.Results1137 patients were studied (mean±sdage 67±10 years; 56.9% male; mean forced expiratory volume in 1 s 56.3% predicted; Global Initiative for Chronic Obstructive Lung Disease B and E stages 66% and 19%, respectively; mean CAT score 17.5). Therapy step-up was observed in 59.3%, treatment switch in 21.7% and step-down in 19.0% of patients. Triple therapy comprised the biggest proportion of inhalation treatment (53.3%). Physicians reported lung function, symptom burden and exacerbations as the main reasons for step-up or step-down, whereas switches within the same treatment class were predominantly caused by device issues. Predictors for step-up were comorbid asthma and exacerbations among others.ConclusionsSTEP was the first study to investigate COPD therapy changes in clinical routine in Austria. The most frequent treatment adjustment was step-up, followed by treatment switch and step-down. Symptom burden, stable or improved lung function and inhalation device handling were the most frequently given reasons for adjustments.
Real-world walking cadence in people with COPD
Authors: Delgado-Ortiz Laura , Ranciati Saverio , Arbillaga-Etxarri Ane , Balcells Eva , Buekers Joren , Demeyer Heleen , Frei Anja , Gimeno-Santos Elena , Hopkinson Nicholas S. , de Jong Corina , Karlsson Niklas , Louvaris Zafeiris , Palmerini Luca , Polkey Michael I. , Puhan Milo A. , Rabinovich Roberto A. , Rodríguez Chiaradia Diego A. , Rodriguez-Roisin Robert , Toran-Montserrat Pere , Vogiatzis Ioannis , Watz Henrik , Troosters Thierry , Garcia-Aymerich Judith 
Published: January 2024

IntroductionThe clinical validity of real-world walking cadence in people with COPD is unsettled. Our objective was to assess the levels, variability and association with clinically relevant COPD characteristics and outcomes of real-world walking cadence.MethodsWe assessed walking cadence (steps per minute during walking bouts longer than 10 s) from 7 days’ accelerometer data in 593 individuals with COPD from five European countries, and clinical and functional characteristics from validated questionnaires and standardised tests. Severe exacerbations during a 12-month follow-up were recorded from patient reports and medical registries.ResultsParticipants were mostly male (80%) and had mean±sdage of 68±8 years, post-bronchodilator forced expiratory volume in 1 s (FEV1) of 57±19% predicted and walked 6880±3926 steps·day−1. Mean walking cadence was 88±9 steps·min−1, followed a normal distribution and was highly stable within-person (intraclass correlation coefficient 0.92, 95% CI 0.90–0.93). After adjusting for age, sex, height and number of walking bouts in fractional polynomial or linear regressions, walking cadence was positively associated with FEV1,6-min walk distance, physical activity (steps·day−1, time in moderate-to-vigorous physical activity, vector magnitude units, walking time, intensity during locomotion), physical activity experience and health-related quality of life and negatively associated with breathlessness and depression (all p<0.05). These associations remained after further adjustment for daily steps. In negative binomial regression adjusted for multiple confounders, walking cadence related to lower number of severe exacerbations during follow-up (incidence rate ratio 0.94 per step·min−1, 95% CI 0.91–0.99, p=0.009).ConclusionsHigher real-world walking cadence is associated with better COPD status and lower severe exacerbations risk, which makes it attractive as a future prognostic marker and clinical outcome.