bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real life evaluation of the multi-organ effects of Lumacaftor/Ivacaftor on F508del homozygous cystic fibrosis patients
Authors: Yaacoby-Bianu Karin , Schnapp Zeev , Koren Ilana , Ilivitzki Anat , Khatib Mohamed , Shorbaji Nadeem , Shteinberg Michal , Livnat Galit 
Published: October 2022

Abstract
Background
Lumacaftor/Ivacaftor (LUM-IVA), a cystic fibrosis transmembrane conductance regulator (CFTR) protein corrector-potentiator combination, improves lung function and reduces pulmonary exacerbations (PEx) in F508del homozygous CF patients. However, the systemic effects of LUM-IVA outside the respiratory system have not yet been thoroughly investigated.

Methods
A prospective, real-world, yearlong study was performed on F508del homozygous adult CF patients who commenced treatment with LUM-IVA. Pancreatic function, bone metabolism, fertility status, nutritional and pulmonary factors were evaluated.

Results
Twelve patients, mean age 28.3 years (18.6–43.9) were recruited. Following 12 months of treatment, no changes were detected in glucose, insulin, c-peptide or BMI values. A significant relative decrease in mean alkaline-phosphatase levels (122.8 U/L vs 89.4, p = 0.002) and a trend toward an increase in calcium levels (9.5 vs 9.9 mg/dL, p = 0.074) were observed. A non-significant improvement in mean DEXA spine t-score after a year of treatment (-2.1 vs -1.6, n = 4, p = 0.11) was detected. Sweat chloride concentrations decreased significantly (-21.4 mEq/L; p = 0.003). Pulmonary outcome revealed improvement in spirometry values during the first three months (FEV1 by 5.7% p = 0.009, FEF25-75 by 4.3% p = 0.001) with no change in chest CT Bhalla score and CFQR after one year. There was also a significant decrease in parenteral antibiotic events (17 vs 8, p = 0.039) with shift from IV to oral antibiotics for PEx treatment.

Conclusions
After one year of treatment, stabilization was observed in the pancreatic indices, nutritional status, structure and function of the lungs, with a beneficial effect on bone mineral metabolism and CFTR function. Additional studies should investigate the effect of CFTR modulators on extra-pulmonary manifestations.
Genetically modified organisms: adapting regulatory frameworks for evolving genome editing technologies
Authors: Rozas Pablo , Kessi-Pérez Eduardo I. , Martínez Claudio 
Published: October 2022

AbstractGenetic modification of living organisms has been a prosperous activity for research and development of agricultural, industrial and biomedical applications. Three decades have passed since the first genetically modified products, obtained by transgenesis, become available to the market. The regulatory frameworks across the world have not been able to keep up to date with new technologies, monitoring and safety concerns. New genome editing techniques are opening new avenues to genetic modification development and uses, putting pressure on these frameworks. Here we discuss the implications of definitions of living/genetically modified organisms, the evolving genome editing tools to obtain them and how the regulatory frameworks around the world have taken these technologies into account, with a focus on agricultural crops. Finally, we expand this review beyond commercial crops to address living modified organism uses in food industry, biomedical applications and climate change-oriented solutions.
The impact of intravenously administered dexketoprofen trometamol on analgesia and recovery in ambulatory dilatation and curettage procedures: a retrospective analysis
Authors: Yalçın Naime , Şahin Ayça S. , Sandal Barış , Derbent Abdurrahim , Salihoğlu Ziya 
Published: October 2022

AbstractBackgroundAchieving adequate pain control during and after the uterine D/C (dilatation and curettage) procedure is crucial for a good recovery process and early discharge.The study was conducted to find out whether intravenous dexketoprofen trometamol is more effective than tramadol and paracetamol in easing pain during the D/C procedure as well as to assess its effectiveness in the recovery period.ResultsSignificant differences were determined between the groups regarding the values of Ramsey sedation scores (p=0.048). VAS (visual analog scale) mean values of group T were higher compared to the VAS mean values of group D (p=0.02). A significant difference was found between group P and group D (p=0.016), the mean VAS values of group P were higher than group D.ConclusionsWe found out that preemptive intravenous 25 mg dexketoprofen trometamol administered in the daily D/C procedure provides good quality postoperative analgesia with minimal adverse effects by reducing the need for rescue analgesia, and is more effective in postoperative analgesia than paracetamol and tramadol.
Health Benefits and Cost-Effectiveness of Children's Oncology Group Breast Cancer Screening Guidelines for Chest-Irradiated Hodgkin Lymphoma Survivors
Authors: Wong F. Lennie , Lee Janie M. , Leisenring Wendy M. , Neglia Joseph P. , Howell Rebecca M. , Smith Susan A. , Oeffinger Kevin C. , Moskowitz Chaya S. , Henderson Tara O. , Mertens Ann , Nathan Paul C. , Yasui Yutaka , Landier Wendy , Armstrong Gregory T. , Robison Leslie L. , Bhatia Smita 
Published: October 2022

PURPOSE To evaluate the outcomes and cost-effectiveness of the Children's Oncology Group Guideline recommendation for breast cancer (BC) screening using mammography (MAM) and breast magnetic resonance imaging (MRI) in female chest-irradiated childhood Hodgkin lymphoma (HL) survivors. Digital breast tomosynthesis (DBT), increasingly replacing MAM in practice, was also examined. METHODS Life years (LYs), quality-adjusted LYs (QALYs), BC mortality, health care costs, and false-positive screen frequencies of undergoing annual MAM, DBT, MRI, MAM + MRI, and DBT + MRI from age 25 to 74 years were estimated by microsimulation. BC risks and non-BC mortality were estimated from female 5-year survivors of HL in the Childhood Cancer Survivor Study and the US population. Test performance of MAM and MRI was synthesized from HL studies, and that of DBT from the general population. Costs (2017 US dollars [USD]) and utility weights were obtained from the medical literature. Incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS With 100% screening adherence, annual BC screening extended LYs by 0.34-0.46 years over no screening. If the willingness-to-pay threshold to gain a quality-adjusted LY was ICER < $100,000 USD, annual MAM at age 25-74 years was the only cost-effective strategy. When nonadherence was taken into consideration, only annual MAM at age 30-74 years (ICER = $56,972 USD) was cost-effective. Supplementing annual MAM with MRI costing $545 USD was not cost-effective under either adherence condition. If MRI costs were reduced to $300 USD, adding MRI to annual MAM at age 30-74 years could become more cost-effective, particularly in the reduced adherence condition (ICER = $133,682 USD). CONCLUSION Annual BC screening using MAM at age 30-74 years is effective and cost-effective in female chest-irradiated HL survivors. Although annual adjunct MRI is not cost-effective at $545 USD cost, it could become cost-effective as MRI cost is reduced, a plausible scenario with the emergent use of abbreviated MRI.
Low-Dose Immunotherapy in Head and Neck Cancer: A Randomized Study
Authors: Patil Vijay Maruti , Noronha Vanita , Menon Nandini , Rai Rahul , Bhattacharjee Atanu , Singh Ajay , Nawale Kavita , Jogdhankar Shweta , Tambe Rupali , Dhumal Sachin , Sawant Riddhi , Alone Mitali , Karla Devanshi , Peelay Zoya , Pathak Shruti , Balaji Arun , Kumar Suman , Purandare Nilendu , Agarwal Archi , Puranik Ameya , Mahajan Abhishek , Janu Amit , Kumar Singh Gunjesh , Mittal Neha , Yadav Subhash , Banavali Shripad , Prabhash Kumar 
Published: October 2022

PURPOSE The regimens approved for the treatment of advanced head and neck squamous cell carcinoma are accessible to only 1%-3% of patients in low- and middle-income countries because of their cost. In our previous study, metronomic chemotherapy improved survival in this setting. Retrospective data suggest that a low dose of nivolumab may be efficacious. Hence, we aimed to assess whether the addition of low-dose nivolumab to triple metronomic chemotherapy (TMC) improved overall survival (OS). METHODS This was a randomized phase III superiority study. Adult patients with recurrent or newly diagnosed advanced head and neck squamous cell carcinoma being treated with palliative intent with an Eastern Cooperative Oncology Group performance status of 0-1 were eligible. Patients were randomly assigned 1:1 to TMC consisting of oral methotrexate 9 mg/m2 once a week, celecoxib 200 mg twice daily, and erlotinib 150 mg once daily, or TMC with intravenous nivolumab (TMC-I) 20 mg flat dose once every 3 weeks. The primary end point was 1-year OS. RESULTS One hundred fifty-one patients were randomly assigned, 75 in TMC and 76 in the TMC-I arm. The addition of low-dose nivolumab led to an improvement in the 1-year OS from 16.3% (95% CI, 8.0 to 27.4) to 43.4% (95% CI, 30.8 to 55.3; hazard ratio, 0.545; 95% CI, 0.362 to 0.820; P = .0036). The median OS in TMC and TMC-I arms was 6.7 months (95% CI, 5.8 to 8.1) and 10.1 months (95% CI, 7.4 to 12.6), respectively ( P = .0052). The rate of grade 3 and above adverse events was 50% and 46.1% in TMC and TMC-I arms, respectively ( P = .744). CONCLUSION To our knowledge, this is the first-ever randomized study to demonstrate that the addition of low-dose nivolumab to metronomic chemotherapy improved OS and is an alternative standard of care for those who cannot access full-dose checkpoint inhibitors.
Association Between Remote Monitoring and Acute Care Visits in High-Risk Patients Initiating Intravenous Antineoplastic Therapy
Authors: Daly Bobby , Nicholas Kevin J. , Flynn Jessica , Panageas Katherine S. , Silva Nicholas , Duck Elaine , Zervoudakis Alice , Holland Jessie , Salvaggio Rori , Begue Aaron , Wagner Isaac , Sokolowski Stefania , Zablocki Melissa , Chiu Yeneat O. , Kuperman Gilead J. , Simon Brett A. , Perchick Wendy , Reidy‐Lagunes Diane L. 
Published: October 2022

PURPOSE: Traditional oncology care models have not effectively identified and managed at-risk patients to prevent acute care. A next step is to harness advances in technology to enable patients to report symptoms any time, enabling digital hovering—intensive symptom monitoring and management. Our objective was to evaluate a digital platform that identifies and remotely monitors high-risk patients initiating antineoplastic therapy with the goal of preventing acute care visits. METHODS: This was a single-institution matched cohort quality improvement study conducted at a National Cancer Institute–designated cancer center between January 1, 2019, and March 31, 2020. Eligible patients were those initiating intravenous antineoplastic therapy who were identified as high risk for seeking acute care. Enrolled patients' symptoms were monitored using a digital platform. A dedicated team of clinicians managed reported symptoms. The primary outcomes of emergency department visits and hospitalizations within 6 months of treatment initiation were analyzed using cumulative incidence analyses with a competing risk of death. RESULTS: Eighty-one patients from the intervention arm were matched by stage and disease with contemporaneous high-risk control patients. The matched cohort had similar baseline characteristics. The cumulative incidence of an emergency department visit for the intervention cohort was 0.27 (95% CI, 0.17 to 0.37) at six months compared with 0.47 (95% CI, 0.36 to 0.58) in the control ( P = .01) and of an inpatient admission was 0.23 (95% CI, 0.14 to 0.33) in the intervention cohort versus 0.41 (95% CI, 0.30 to 0.51) in the control ( P = .02). CONCLUSION: The narrow employment of technology solutions to complex care delivery challenges in oncology can improve outcomes and innovate care. This program was a first step in using a digital platform and a remote team to improve symptom care for high-risk patients.
Regulation of Porcine Oviduct Epithelium Functions via Progesterone and Estradiol Is Influenced by Cortisol
Authors: Du Shuaizhi , Trakooljul Nares , Palma-Vera Sergio E , Murani Eduard , Schuler Gerhard , Schoen Jennifer , Chen Shuai 
Published: October 2022

AbstractPreimplantation maternal stress, characterized by elevated glucocorticoids (GCs), has been linked to reproductive failures caused by impaired oviduct functionality, which is known to be predominantly regulated by the sex steroids, progesterone (P4) and (17)estradiol (E2). Although steroid receptors share analogous structures and binding preferences, the interaction between GCs and E2/P4 in the oviduct has attracted little attention. Using an air-liquid interface culture model, porcine oviduct epithelial cells were stimulated with single (cortisol, E2, P4) or hormone mixtures (cortisol/E2, cortisol/P4) for 12 hours and 72 hours. Cultures were subsequently assessed for epithelial morphometry, bioelectrical properties, and gene expression responses (steroid hormone signaling, oviductal function, immune response, and apoptosis). Results confirmed the suppressive role of P4 in regulating oviduct epithelium characteristics, which was partially opposed by E2. Besides increasing the ratio of ciliated cells, cortisol antagonized the effect of P4 on epithelial polarity and modified sex steroid–induced changes in transepithelial electrical properties. Both sex steroids affected the glucocorticoid receptor expression, while cortisol downregulated the expression of progesterone receptor. The overall gene expression pattern suggests that sex steroid dominates the cotreatment, but cortisol contributes by altering the gene responses to sex steroids. We conclude that besides its individual action, maternal cortisol interplays with sex steroids at phenotypic and molecular levels in the oviduct epithelium, thereby influencing the microenvironment of gametes and early embryos.
TERFism, Zionism, and Right-Wing Annihilationism
Authors: Schotten C. Heike 
Published: October 2022

Abstract
This article traces the emergence of what the author calls predation TERFism to the development of US Jewish-identified feminism and, in particular, Zionist lesbian separatism. This historical connection is reflected in the rhetorical and ideological similarities between predation TERFism and Zionism, both of which are defined by an “extinction phobia” that confuses oppressor and oppressed, presenting the subordinate party as capable of eliminating the dominant one. This extinction phobia transforms into “right-wing annihilationism” via a dehumanization of the subordinate party as innately harmful and therefore requiring elimination; hence the hallmark predation TERF abjection of trans women as rapists of cis women and the Zionist abjection of Palestinians as “savage” and/or “terrorist.” These connections can be obscured by the siloization of social justice movement work in the United States, wherein anti-colonial and anti-imperial organizing is often separated from organizing for gender and reproductive justice and sexual freedom. Recognizing the continuities, however—whether historical, material, or ideological—between predation TERFism and Zionism offers useful lessons for understanding not only the power of the contemporary global anti-trans resurgence, but also how we might build solidaristic, anti-colonial movements to defeat it.
Effect of active shortening and stretching on the rate of force re-development in rabbit psoas muscle fibres
Authors: Ames Spencer R. , Joumaa Venus , Herzog Walter 
Published: October 2022

ABSTRACTThe steady-state isometric force produced by skeletal muscle after active shortening and stretching is depressed and enhanced, respectively, compared with purely isometric force produced at corresponding final lengths and at the same level of activation. One hypothesis proposed to account for these force depression (FD) and force enhancement (FE) properties is a change in cross-bridge cycling kinetics. The rate of cross-bridge attachment (f) and/or cross-bridge detachment (g) may be altered following active shortening and active stretching, leading to FD and FE, respectively. Experiments elucidating cross-bridge kinetics in actively shortened and stretched muscle preparations and their corresponding purely isometric contractions have yet to be performed. The aim of this study was to investigate cross-bridge cycling kinetics of muscle fibres at steady-state following active shortening and stretching. This was done by determining muscle fibre stiffness and rate of active force redevelopment following a quick release–re-stretch protocol (kTR). Applying these measures to equations previously used in the literature for a two-state cross-bridge cycling model (attached/detached cross-bridges) allowed us to determine apparent f and g, the proportion of attached cross-bridges, and the force produced per cross-bridge. kTR, apparent f and g, the proportion of attached cross-bridges and the force produced per cross-bridge were significantly decreased following active shortening compared with corresponding purely isometric contractions, indicating a change in cross-bridge cycling kinetics. Additionally, we showed no change in cross-bridge cycling kinetics following active stretch compared with corresponding purely isometric contractions. These findings suggest that FD is associated with changes in cross-bridge kinetics, whereas FE is not.
Fatty acid oxidation: a neglected factor in understanding the adjustment of mitochondrial function to cold temperatures
Authors: Mast Heather , Holody Claudia D. , Lemieux Hélène 
Published: October 2022

ABSTRACT
For ectothermic species, adaptation to thermal changes is of critical importance. Mitochondrial oxidative phosphorylation (OXPHOS), which leverages multiple electron pathways to produce energy needed for survival, is among the crucial metabolic processes impacted by temperature. Our aim in this study was to identify how changes in temperature affect the less-studied electron transferring flavoprotein pathway, fed by fatty acid substrates. We used the planarian Dugesia tigrina, acclimated for 4 weeks at 10°C (cold acclimated) or 20°C (normothermic). Respirometry experiments were conducted at an assay temperature of either 10 or 20°C to study specific states of the OXPHOS process using the fatty acid substrates palmitoylcarnitine (long chain), octanoylcarnitine (medium chain) or acetylcarnitine (short chain). Following cold acclimation, octanoylcarnitine exhibited increases in both the OXPHOS and electron transfer (ET, non-coupled) states, indicating that the pathway involved in medium-chain length fatty acids adjusts to cold temperatures. Acetylcarnitine only showed an increase in the OXPHOS state as a result of cold acclimation, but not in the ET state, indicative of a change in phosphorylation system capacity rather than fatty acid β-oxidation. Palmitoylcarnitine oxidation was unaffected. Our results show that cold acclimation in D. tigrina caused a specific adjustment in the capacity to metabolize medium-chain fatty acids rather than an adjustment in the activity of the enzymes carnitine-acylcarnitine translocase, carnitine acyltransferase and carnitine palmitoyltransferase-2. Here, we provide novel evidence of the alterations in fatty acid β-oxidation during cold acclimation in D. tigrina.
Effectiveness of forest honey (Apis dorsata) as therapy for ovarian failure causing malnutrition
Authors: Safitri Erma , Purnobasuki Hery , Purnama Muhammad Thohawi Elziyad , Chhetri Shekhar 
Published: October 2022

Background:Malnutrition is the imbalance between intake and nutritional needs, resulting in a decrease in body weight, composition, and physical function. Malnutrition causes infertility due to intestinaland liver degeneration,which may progress to testicular and ovarian degeneration.Methods:An infertile female rat model with a degenerative ovary was induced with malnutrition through a 5-day food fasting but still had drinking water. The administration of (T1) 30% (v/v) and (T2) 50% (v/v) forest honey (Apis dorsata) were performed for ten consecutive days, whereas the (T+) group was fasted and not administered forest honey and the (T−) group has not fasted and not administered forest honey. Superoxide dismutase, malondialdehyde, IL-13 and TNF-α cytokine expressions, and ovarian tissue regeneration were analyzed.Results:Superoxide dismutase was significantly different (p<0.05) in T1 (65.24±7.53), T2 (74.16±12.3), and T− (65.09±6.56) compared with T+ (41.76±8.51). Malondialdehyde was significantly different (p<0.05) in T1 (9.71±1.53), T2 (9.23±0.96), and T− (9.83±1.46) compared with T+ (15.28±1.61). Anti-inflammatory cytokine (IL-13) expression was significantly different (p<0.05) in T1 (5.30±2.31), T2 (9.80±2.53), and T− (0.30±0.48) compared with T+ (2.70±1.57). Pro-inflammatory cytokine (TNF-α) expression was significantly different (p<0.05) in T1 (4.40±3.02), T2 (2.50±1.65), and T− (0.30±0.48) compared with T+ (9.50±1.78). Ovarian tissue regeneration was significantly different (p<0.05) in T− (8.6±0.69) and T2 (5.10±0.99) compared with T1 (0.7±0.95) and T+ (0.3±0.67).Conclusion:The 10-day administration of 50% (v/v) forest honey can be an effective therapy for ovarian failure that caused malnutrition in the female rat model.
Metabolites of Pinang Yaki (Areca vestiaria) Fruit Extract: A Metabolite Profiling Study
Authors: Simbala Herny Emma Inonta , Nurkolis Fahrul , Mayulu Nelly , Rotty Linda Wilhelma Ancella 
Published: October 2022

Background: Pinang yaki has bioactive compounds that have potential as a new herbal supplement, but their metabolites profil is lack of data. A better understanding of the bioactive compounds of pinang yaki using untargeted metabolomic profiling studies will provide clearer insight into the health benefits of pinang yaki in further. Methods: Fresh samples of pinang yaki (Areca vestiaria) are obtained from forests in North Sulawesi Province, Indonesia. Samples were used for untargeted metabolomics analysis by UHPLC-MS. Results: Based on an untargeted metabolomic profiling study of pinang yaki, 2504 compounds in ESI- and 2645 compounds in ESI+ were successfully obtained. After the analysis, 356 compounds in ESI- and 543 compounds in ESI+ were identified successfully. Major compounds Alpha-Chlorohydrin (PubChem ID: 7290) and Tagatose (PubChem ID: 439312) were found in ESI+ and ESI-. Discussion: The 10 metabolites from pinang yaki extract (ESI+) also have been indicated in preventing viral infection and have exhibited good neuroprotective immunity. Benzothiazole (PubChem ID: 7222), L-isoleucine (PubChem ID: 6306), D-glucono-delta-lactone (PubChem ID: 736), Diethylpyrocarbonate (PubChem ID: 3051), Bis(2-Ethylhexyl) amine (PubChem ID: 7791), Cinnamic acid (PubChem ID: 444539), and Trigonelline (PubChem ID: 5570) also had potential effects as an antiviral and anti-inflammatory. Conclusion: Untargeted metabolomic profiling showed many bioactive compounds contained in pinang yaki (Areca vestiaria) extract. The top 10 compounds capable to ionize well have been identified and explored for their potential benefits as antiviral supplement products by literature study. This is a preliminary study which still needs further research such as in vitro, preclinical, and clinical trials.