bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Pathological Complete Response to Neoadjuvant Alectinib in a Patient With Resectable ALK-Positive Non-Small Cell Lung Cancer
Authors: Hu Yan , Ren Siying , Wang Ruoyao , Han Wei , Xiao Peng , Wang Li , Yu Fenglei , Liu Wenliang 
Published: July 2022

Background: Alectinib, a highly selective inhibitor of ALK, is currently used in the first-line setting of untreated advanced ALK-positive NSCLC and in the second-line setting of crizotinib-resistant ALK-positive NSCLC. Despite promising efficacy and tolerability in the treatment of advanced ALK-positive NSCLC, the activity of alectinib as neoadjuvant therapy in resectable ALK-positive NSCLC remains to be investigated.Case presentation: Herein, we report a case of a 58-year-old female patient presented to our hospital with hemoptysis for 1 month. Contrast-enhanced computerized tomography (CT) of the chest showed an approximately 4.2 × 3.4 cm mass in the right hilum with localized obstructive pneumonia in the right lower lobe and multiple enlarged lymph nodes in the right hilum and mediastinum. Serum oncological markers results showed elevated levels of CA19-9, CEA, CA125, and CA242. Bronchoscopic biopsy of the mass showed poorly differentiated pulmonary adenocarcinoma and immunohistochemical testing results confirmed ALK positivity. Neoadjuvant alectinib was given at a dosage of 600 mg twice per day for two cycles (56 days), achieving a partial response of the disease with 90% shrinkage of the mass at the subsequent whole-body positron emission tomography. Repeat serum oncological markers results showed that only CA125 was elevated, but lower than before therapy. A bilobectomy of the right middle and lower lobes and systemic lymphadectomy under video-assisted thoracoscopic approach was successfully performed 7 days after the last dose of alectinib. Postoperative pathology showed pathological complete response (pCR). The patient experienced an uneventful postoperative course and continued to receive alectinib and did not report any specific discomfort at her 8-month follow-up. Thoracoabdominal CT at 8 months postoperatively showed no recurrence and repeated examination of serum oncological markers were negative.Conclusion: We report a case of resectable ALK-positive NSCLC treated with neoadjuvant aletinib achieving pCR. Our case highlights the feasibility of alectinib as neoadjuvant therapy for the treatment of resectable ALK-positive NSCLC. Undoubtedly, the safety and efficacy of this novel treatment modality needs to be explored in future large clinical trials.
Progress in Research on Antitumor Drugs and Dynamic Changes in Skeletal Muscles
Authors: Xu Ting , Li Zhen-Hao , Liu Ting , Jiang Cai-Hong , Zhang Ya-Juan , Li Hui , Jiang Ying , Zhao Juan , Guo Wen-Jing , Guo Jia-Yuan , Wang Lu , Li Jia-Xuan , Shen Jing , Jin Gao-Wa , Zhang Ze-Wei , Li Quan-Fu 
Published: July 2022

Objective: To review the research progress of reltionship between antitumor drugs and the dynamic changes of the skeletal muscles during treatment phase.Background: Sarcopenia is a common disease in patients with tumors, and it has been agreed that patients with tumors and sarcopenia experience more serious adverse reactions and have a shorter long-term survival after antitumor therapy than patients without sarcopenia. Antitumor drugs whilst beneficial for tumor regression, interferes and synergizes with cancer-induced muscle wasting/sarcopenia, induced myodemia or intramuscular fat and the two conditions often overlap making it difficult to drive conclusions. In recent years, increasing attention has been paid to the dynamic changes in skeletal muscles during antitumor drug therapy. Dynamic changes refer not only measurement skeletal muscle quantity at baseline level, but give more emphasis on the increasing or decreasing level during or end of the whole treatment course.Methods: We retrievaled published English-language original research articles via pubmed, those studies mainly focused on repeated measurements of skeletal muscle index using computed tomography (CT) in cancer patients who received antitumor drug treatment but not received interventions that produced muscle mass change (such as exercise and nutritional interventions).Conclusion: This article will summarize the research progress to date. Most of antineoplastic drug cause skeletal muscle loss during the treatment course, loss of L3 skeletal muscle index is always associated with poor clinical outcomes.
Vaccine Safety Surveillance Using Routinely Collected Healthcare Data—An Empirical Evaluation of Epidemiological Designs
Authors: Schuemie Martijn J. , Arshad Faaizah , Pratt Nicole , Nyberg Fredrik , Alshammari Thamir M , Hripcsak George , Ryan Patrick , Prieto-Alhambra Daniel , Lai Lana Y. H. , Li Xintong , Fortin Stephen , Minty Evan , Suchard Marc A. 
Published: July 2022

Background: Routinely collected healthcare data such as administrative claims and electronic health records (EHR) can complement clinical trials and spontaneous reports to detect previously unknown risks of vaccines, but uncertainty remains about the behavior of alternative epidemiologic designs to detect and declare a true risk early.Methods: Using three claims and one EHR database, we evaluate several variants of the case-control, comparative cohort, historical comparator, and self-controlled designs against historical vaccinations using real negative control outcomes (outcomes with no evidence to suggest that they could be caused by the vaccines) and simulated positive control outcomes.Results: Most methods show large type 1 error, often identifying false positive signals. The cohort method appears either positively or negatively biased, depending on the choice of comparator index date. Empirical calibration using effect-size estimates for negative control outcomes can bring type 1 error closer to nominal, often at the cost of increasing type 2 error. After calibration, the self-controlled case series (SCCS) design most rapidly detects small true effect sizes, while the historical comparator performs well for strong effects.Conclusion: When applying any method for vaccine safety surveillance we recommend considering the potential for systematic error, especially due to confounding, which for many designs appears to be substantial. Adjusting for age and sex alone is likely not sufficient to address differences between vaccinated and unvaccinated, and for the cohort method the choice of index date is important for the comparability of the groups. Analysis of negative control outcomes allows both quantification of the systematic error and, if desired, subsequent empirical calibration to restore type 1 error to its nominal value. In order to detect weaker signals, one may have to accept a higher type 1 error.
Novel Gemcitabine-Re(I) Bisquinolinyl Complex Combinations and Formulations With Liquid Crystalline Nanoparticles for Pancreatic Cancer Photodynamic Therapy
Authors: Liew Hui Shan , Mai Chun-Wai , Zulkefeli Mohd , Madheswaran Thiagarajan , Kiew Lik Voon , Pua Lesley Jia Wei , Hii Ling Wei , Lim Wei Meng , Low May Lee 
Published: July 2022

With less than 10% of 5-year survival rate, pancreatic ductal adenocarcinoma (PDAC) is known to be one of the most lethal types of cancer. Current literature supports that gemcitabine is the first-line treatment of PDAC. However, poor cellular penetration of gemcitabine along with the acquired and intrinsic chemoresistance of tumor against it often reduced its efficacy and hence necessitates the administration of high gemcitabine dose during chemotherapy. Photodynamic therapy (PDT), a more selective and minimally invasive treatment, may be used synergistically with gemcitabine to reduce the doses utilized and dose-related side effects. This study reports the synergistic use of Re(I) bisquinolinyl complex, a transition metal complex photosensitizer with gemcitabine against PDAC. Re(I) bisquinolinyl complex was found to act synergistically with gemcitabine against PDAC in vitro at various ratios. With the aim to enhance cellular uptake and therapeutic efficiency, the Re(I) bisquinolinyl complex and gemcitabine were encapsulated into liquid crystalline nanoparticles (LCNPs) system. The formulations were found to produce homogeneous drug-loaded LCNPs (average size: 159–173 nm, zeta potential +1.06 to −10 mV). Around 70% of gemcitabine and 90% of the Re(I) bisquinolinyl complex were found to be entrapped efficiently in the formulated LCNPs. The release rate of gemcitabine or/and the Re(I) bisquinolinyl complex loaded into LCNPs was evaluated in vitro, and the hydrophilic gemcitabine was released at a faster rate than the lipophilic Re(I) complex. LCNPs loaded with gemcitabine and Re(I) bisquinolinyl complex in a 1:1 ratio illustrated the best anti-cancer activity among the LCNP formulations (IC50 of BxPC3: 0.15 μM; IC50 of SW 1990: 0.76 μM) through apoptosis. The current findings suggest the potential use of transition metal-based photosensitizer as an adjunctive agent for gemcitabine-based chemotherapy against PDAC and the importance of nano-formulation in such application.
Beneficial Role of Blood Flow Restriction Exercise in Heart Disease and Heart Failure Using the Muscle Hypothesis of Chronic Heart Failure and a Growing Literature
Authors: Cahalin Lawrence P. , Formiga Magno F. , Owens Johnny , Anderson Brady , Hughes Luke 
Published: July 2022

Background: Blood flow restriction exercise (BFRE) has become a common method to increase skeletal muscle strength and hypertrophy for individuals with a variety of conditions. A substantial literature of BFRE in older adults exists in which significant gains in strength and functional performance have been observed without report of adverse events. Research examining the effects of BFRE in heart disease (HD) and heart failure (HF) appears to be increasing for which reason the Muscle Hypothesis of Chronic Heart Failure (MHCHF) will be used to fully elucidate the effects BFRE may have in patients with HD and HF highlighted in the MHCHF.Methods: A comprehensive literature review was performed in PubMed and the Cochrane library through February 2022. Inclusion criteria were: 1) the study was original research conducted in human subjects older than 18 years of age and diagnosed with either HD or HF, 2) study participants performed BFRE, and 3) post-intervention outcome measures of cardiovascular function, physical performance, skeletal muscle function and structure, and/or systemic biomarkers were provided. Exclusion criteria included review articles and articles on viewpoints and opinions of BFRE, book chapters, theses, dissertations, and case study articles.Results: Seven BFRE studies in HD and two BFRE studies in HF were found of which four of the HD and the two HF studies examined a variety of measures reflected within the MHCHF over a period of 8–24 weeks. No adverse events were reported in any of the studies and significant improvements in skeletal muscle strength, endurance, and work as well as cardiorespiratory performance, mitochondrial function, exercise tolerance, functional performance, immune humoral function, and possibly cardiac performance were observed in one or more of the reviewed studies.Conclusion: In view of the above systematic review, BFRE has been performed safely with no report of adverse event in patients with a variety of different types of HD and in patients with HF. The components of the MHCHF that can be potentially improved with BFRE include left ventricular dysfunction, inflammatory markers, inactivity, a catabolic state, skeletal and possibly respiratory muscle myopathy, dyspnea and fatigue, ANS activity, and peripheral blood flow. Furthermore, investigation of feasibility, acceptability, adherence, adverse effects, and symptoms during and after BFRE is needed since very few studies have examined these important issues comprehensively in patients with HD and HF.
Insight Into the Metabolic Adaptations of Electrically Pulse-Stimulated Human Myotubes Using Global Analysis of the Transcriptome and Proteome
Authors: Mengeste Abel M. , Nikolić Nataša , Dalmao Fernandez Andrea , Feng Yuan Z. , Nyman Tuula A. , Kersten Sander , Haugen Fred , Kase Eili Tranheim , Aas Vigdis , Rustan Arild C. , Thoresen G. Hege 
Published: July 2022

Electrical pulse stimulation (EPS) has proven to be a useful tool to interrogate cell-specific responses to muscle contraction. In the present study, we aimed to uncover networks of signaling pathways and regulatory molecules responsible for the metabolic effects of exercise in human skeletal muscle cells exposed to chronic EPS. Differentiated myotubes from young male subjects were exposed to EPS protocol 1 (i.e. 2 ms, 10 V, and 0.1 Hz for 24 h), whereas myotubes from middle-aged women and men were exposed to protocol 2 (i.e. 2 ms, 30 V, and 1 Hz for 48 h). Fuel handling as well as the transcriptome, cellular proteome, and secreted proteins of EPS-treated myotubes from young male subjects were analyzed using a combination of high-throughput RNA sequencing, high-resolution liquid chromatography-tandem mass spectrometry, oxidation assay, and immunoblotting. The data showed that oxidative metabolism was enhanced in EPS-exposed myotubes from young male subjects. Moreover, a total of 81 differentially regulated proteins and 952 differentially expressed genes (DEGs) were observed in these cells after EPS protocol 1. We also found 61 overlapping genes while comparing the DEGs to mRNA expression in myotubes from the middle-aged group exposed to protocol 2, assessed by microarray. Gene ontology (GO) analysis indicated that significantly regulated proteins and genes were enriched in biological processes related to glycolytic pathways, positive regulation of fatty acid oxidation, and oxidative phosphorylation, as well as muscle contraction, autophagy/mitophagy, and oxidative stress. Additionally, proteomic identification of secreted proteins revealed extracellular levels of 137 proteins were changed in myotubes from young male subjects exposed to EPS protocol 1. Selected putative myokines were measured using ELISA or multiplex assay to validate the results. Collectively, our data provides new insight into the transcriptome, proteome and secreted proteins alterations following in vitro exercise and is a valuable resource for understanding the molecular mechanisms and regulatory molecules mediating the beneficial metabolic effects of exercise.
Interest in Co-located Reproductive and Sexual Health Services Among Women and Men Receiving Medication for Opioid Use Disorder in an Outpatient Treatment Clinic
Authors: Stoltman Jonathan J. K. , Lander Laura R. , Patrick Julie H. , Terplan Mishka , Jones Hendrée E. 
Published: July 2022

IntroductionReproductive and sexual health (RSH) are core components of comprehensive care, yet often omitted in addiction treatment. We characterize knowledge of and interest in RSH services and contraceptive method awareness and use in a rural, Appalachian outpatient clinic.Materials and MethodsBetween September 2016 and April 2018, a convenience sample of 225 patients receiving treatment for opioid use disorder at an outpatient buprenorphine/naloxone clinic was collected. Participants completed a cross-sectional RSH survey that included demographics, interest in RSH service integration, contraceptive use, and contraceptive knowledge.ResultsA total of 212 people (126 non-pregnant women, 29 pregnant women, and 57 men) completed the survey of whom 45.8% indicated interest in adding RSH services. Services of interest include regular physical exams (44.8%), STI/STD testing (41.0%), and contraception education and administration (38.2%). There were no significant differences between interest in co-located services between women and men (P = 0.327). Current contraceptive use was low (17.9–30.9%) among women and men. Contraceptive method awareness was 43.3% for high efficacy methods and 50.0% for medium efficacy methods. Women and currently pregnant women knew more total, high, and medium efficacy contraceptive method than men (P = 0.029).DiscussionBoth women and men in this sample are interested in co-located RSH services. Current contraceptive use was low among participants. Contraceptive knowledge was lower among men compared to women, and generally low. Providing co-located RSH services may facilitate RSH education, contraceptive method uptake, and promote engagement across various RSH domains.
A Cross-Sectional Study on Associations Between BDNF, CRP, IL-6 and Clinical Symptoms, Cognitive and Personal Performance in Patients With Paranoid Schizophrenia
Authors: Chumakov Egor , Dorofeikova Mariia , Tsyrenova Kristina , Petrova Nataliia 
Published: July 2022

BackgroundCognitive impairment is among the core dimensions in schizophrenia and is a significant predictor of everyday functioning in people with schizophrenia. Given the enormous burden of schizophrenia, the search for its clinically relevant biomarkers is essential. Researchers have been trying to elucidate factors of cognitive impairment as well as personal performance, but the search is still ongoing. The aim of the study was to search for associations between BDNF, CRP, IL-6 and clinical symptoms, cognitive and personal performance in patients with paranoid schizophrenia.MethodsA total of 86 patients (53.5% women, mean age 31.1 ± 6.5) with paranoid schizophrenia (F20.0; ICD-10) in remission were examined. Clinical and neuropsychological examination included the Positive and Negative Syndrome Scale, Personal and Social Performance Scale, Calgary Depression Scale for Schizophrenia and the Brief Assessment of Cognitive Function in Schizophrenia. IL-6, BDNF, CRP levels were determined in the patients' blood serum.ResultsCognitive impairment was revealed in 79.1% of patients and was more profound in patients with higher number of hospitalizations (p = 0.006). The average BDNF levels were 13.38 ± 15.84 ng/ml, CRP concentration was 2.09 ± 2.54 mg/l, and IL-6 levels were 12.14 ± 5.88 pg/ml. There were no differences in biomarker levels or BACS results in patients that had different antipsychotic therapy or differed in the presence of anticholinergic therapy. CRP levels were higher in patients with longer disease duration, lower age of onset, more impaired personal social performance and processing speed. IL-6 was higher in individuals with lower working memory scores. PANSS negative subscale score negatively correlated and PSP score positively correlated with most cognitive domains. A linear regression established that the first episode vs. multiple episodes of schizophrenia could statistically significantly predict personal and social performance and cognition, including speech fluency and planning, as well as CRP levels.ConclusionsThis study continues the search for biomarkers of schizophrenia and cognitive impairment in schizophrenia to improve the reliability of diagnosing the disorder and find new treatment approaches. The role of the number of psychoses experienced (first episode vs. multiple episodes of schizophrenia) in cognition, personal and social performance and inflammation is shown.
Challenges and Enablers for Smartphone Use by Persons With Vision Loss During the COVID-19 Pandemic: A Report of Two Case Studies
Authors: Senjam Suraj Singh , Primo Susan A. 
Published: July 2022

PurposeStudies have reported that knowledge and skills to operate smartphones among people with profound visual loss are limited especially in low- to middle-income countries as many important functions of smartphones are unknown to them. This report presents smartphone use, its challenges, and enablers in two persons with profound visual impairment while executing their daily routine and instrumental living activities amidst the COVID-19 pandemic.Case selection and interviewDuring the lockdown period, we provided tele (vision) rehabilitation service. From the list of the callers, we purposely selected two callers with significant visual impairment, one woman and one man, to allow us to gather rich information related to smartphone use, enablers, and challenges faced during the usage. A semistructured interview was done to obtain insights into the information. The selection criteria were (1) continuous smartphone use independently for more than 5 years; (2) graduation-level education or higher; and (3) no additional disabilities.DiscussionWe found substantial use of smartphones in executing their daily and instrumental daily living activities by these two participants. The extent of the use of mainstream apps for various tasks was almost equivalent to what we observed among sighted persons. The most important enabling factors were the presence of a screen reader “TalkBack” on Android phones and data connection of the mobile, followed by the ability to assess multiple languages using the text-to-speech feature. A supportive environment from peers or family members is important for the beginner. Poor battery backup, frequent unwanted ads or pop-ups while using the phone, not readable contents with a screen reader, e.g., CAPTCHA, and slow or unresponsiveness of the screen reader were frequent challenges faced by them. Both cases reported that around 80% of daily solutions were helped by using a smartphone.ConclusionsThe current advances in accessible technology of smartphones enable an individual with profound visual loss to use them almost equivalently as a sighted person. To reduce the gap in digital inclusion, people with visual impairment should be encouraged to use the smartphone for their daily solutions with attention to proper training.
Risk Assessment of Chlorothalonil as a Probable Human Carcinogen on Selected Vegetables in an Eastern China Province
Authors: Sun Chen-Xi , Liu Bing , Wang Wen-Bo , Yuan Xue-Xia , Wu Yuan-Juan 
Published: July 2022

ObjectivesThis study aimed to provide an assessment of chlorothalonil's possible carcinogenic risk posed to the public. In combination and comparison with the non-carcinogenic risk, the results hopefully could provide useful insights, early warning, and references for policy formulation.MethodsThis study firstly investigated the occurrence of chlorothalonil on selected key vegetables for different scenarios, and then conducted an exposure assessment with officially published data. Lastly, both the non-carcinogenic and carcinogenic risk of chlorothalonil were calculated by using Monte-Carlo simulation.ResultsEven though mean non-carcinogenic risks of chlorothalonil for all scenarios were below threshold value, the mean carcinogenic risks for maximum-risk scenario and most-likely risk scenario were mostly above threshold value. High probabilities of exceedance of threshold value existed for carcinogenic risk under all scenarios.ConclusionPotential threat to public health existed for conventionally ‘safe' pesticide if considering the possible carcinogenicity. Extra caution should be taken and the potential carcinogenic effects should be included into consideration for better protection of public health during the policy formulation process.