bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of tumor-specific CAP1 expression and body constitution on clinical outcomes in patients with early breast cancer
Authors: Bergqvist Malin , Elebro Karin , Sandsveden Malte , Borgquist Signe , Rosendahl Ann H. 
Published: June 2020

Abstract
Background
Obesity induces molecular changes that may favor tumor progression and metastatic spread, leading to impaired survival outcomes in breast cancer. Adenylate cyclase-associated protein 1 (CAP1), an actin regulatory protein and functional receptor for the obesity-associated adipokine resistin, has been implicated with inferior cancer prognosis. Here, the objective was to investigate the interplay between body composition and CAP1 tumor expression regarding breast cancer outcome through long-term survival analyses.

Methods
Among 718 women with primary invasive breast cancer within the large population-based prospective Malmö Diet and Cancer Study, tumor-specific CAP1 levels were assessed following thorough antibody validation and immunohistochemical staining of tumor tissue microarrays. Antibody specificity and functional application validity were determined by CAP1 gene silencing, qRT-PCR, Western immunoblotting, and cell microarray immunostaining. Kaplan-Meier and multivariable Cox proportional hazard models were used to assess survival differences in terms of breast cancer-specific survival (BCSS) and overall survival (OS) according to body composition and CAP1 expression.

Results
Study participants were followed for up to 25 years (median 10.9 years), during which 239 deaths were observed. Patients with low CAP1 tumor expression were older at diagnosis, displayed anthropometric measurements indicating a higher adiposity status (wider waist and hip, higher body mass index and body fat percentage), and were more prone to have unfavorable tumor characteristics (higher histological grade, higher Ki67, and estrogen receptor (ER) negativity). Overall, patients with CAP1-low tumors had impaired BCSS (adjusted hazard ratio: HRadj = 0.52, 95% CI 0.31–0.88) and OS (HRadj = 0.64, 95% CI 0.44–0.92) compared with patients having high CAP1 tumor expression. Further, analyses stratified according to different anthropometric measures or ER status showed that the CAP1-associated survival outcomes were most pronounced among patients with low adiposity status or ER-positive disease.

Conclusions
Low CAP1 tumor expression was associated with higher body fatness and worse survival outcomes in breast cancer patients with effect modification by adiposity and ER status. CAP1 could be a novel marker for poorer survival outcome in leaner or ER-positive breast cancer patients, highlighting the need for considering body constitution in clinical decision making.
Evaluation of the effects of a drug with fiscalized substance dispensation, health education, and pharmacovigilance continuing education program in Colombia drugstores and drugstores/pharmacies: study protocol of a multicenter, cluster-randomized controlled trial
Authors: Ceballos Mauricio , Salazar-Ospina Andrea , Sabater-Hernández Daniel , Amariles Pedro 
Published: June 2020

Abstract
Background
Health disorders, due to the use of drugs with fiscalized substances, including controlled substances, have become a common problem in Colombia. Multiple reasons can help explain this problem, including self-medication, since access to these drugs may be easier. Also, there is a lack of knowledge that these drugs are safer than illicit drugs. The use of these drugs without a valid medical prescription and follow-up can have negative consequences such as drug abuse, addiction, and overdose, and eventually, have negative health consequences. Pharmacy staff is essential to both assure the correct drug use and minimize prescription errors to help outpatients have better management of their pharmacotherapy. For this reason, it is necessary to increase key competencies like knowledge, skills, and attitudes in the pharmacy staff of ambulatory (outpatients) pharmacies.

Methods
This study is a prospective, cluster-randomized, parallel-group, multicenter trial of drugstores and drugstores/pharmacies (ambulatory pharmacies). The study is designed to determine the effectiveness of a drug with fiscalized substance dispensation, health education, and pharmacovigilance continuing education program in drugstores and drugstores/pharmacies. Pharmacy staff will be randomly selected and assigned to one of the study groups (intervention or control). The intervention group will receive a continuing education program for over 12 months. The control group will receive only general information about the correct use of complex dosage forms. The primary objective is to evaluate the effectiveness of a continuing education program to improve pharmacy staff competencies (knowledge, skills, and attitudes) to improve the ambulatory (outpatient) pharmacy services: dispensation, health education, and pharmacovigilance of drugs with fiscalized substances. The secondary outcomes include (a) processes associated with the management of drugs with fiscalized substances in drugstores and drugstores/pharmacies, including regulation compliance; (b) degree of implementation of ambulatory (outpatient) pharmacy services targeting these drugs in drugstores and drugstores/pharmacies; (c) patient satisfaction with such services; and (d) pharmacy staff satisfaction with the continuing education program.

Discussion
This clinical trial will establish whether providing a continuing education program for the adequate utilization of drugs with fiscalized substances improves pharmacy staff competencies regarding these drugs.

Trial registration
ClinicalTrials.gov NCT03388567. Registered on 28 November 2017. First drugstore or drugstore/pharmacy randomized on December 1, 2018.

Protocol version
0017102017MC
Efficacy and safety of Dingkun pill for female infertility patients with low prognosis undergoing in vitro fertilization-embryo transfer: study protocol for a multicenter, double-blind, randomized, placebo-controlled trial
Authors: Song Jingyan , Ma Ting , Liang Yanlin , Cao Xianling , Sun Zhengao 
Published: June 2020

Abstract
Background
Approximately 15% of couples in the reproductive age are affected by infertility. Women with diminished ovarian reserves (DOR) or with a poor ovarian response (POR) are required to undergo in vitro fertilization and embryo transfer (IVF-ET) to achieve pregnancy. However, studies indicate that poor response to gonadotropin stimulation has been reported in women undergoing IVF-ET. Results from two recent clinical studies in China suggest that traditional Chinese medicine (TCM) formula Dingkun pill (DKP) showed a curative effect by improving the clinical pregnancy rate in women with DOR and POR. However, the heterogeneity of the studies does not allow one to draw a definitive conclusion on the therapeutic effect of DKP. Therefore, the purpose of this study was to investigate the effect of DKP on improving the clinical outcome of pregnancy of IVF-ET in women with low prognosis.

Methods
A multicenter, double-blinded, randomized placebo-controlled trial was conducted. A total of 460 infertile patients undergoing IVF or intracytoplasmic sperm injection (ICSI) were recruited from 12 public hospitals in China. Participants were randomly divided into the experimental group (DKP formula) or the placebo group (control) at a ratio of 1:1. All patients were treated with GnRH antagonist protocol and ovarian stimulation performed for 5 weeks (from the 5th day of the previous menstrual cycle to the day of oocyte retrieval). The patients were followed up for 6 months to record their conception outcome. The primary outcome is to compare the pregnancy outcome to those under placebo treatment. Secondary outcomes included the total count of the retrieved oocyte, embryo quality, endometrial thickness on ET day, implantation rate, and early miscarriage rate.

Discussion
Currently, no multicenter, double-blind, randomized, placebo-controlled trials have been performed on the use of the DKP formula to improve on the clinical outcome of the conception of IVF-ET in women with low prognosis. DKP might provide a good clinical solution for females with low prognosis and undergoing IVF. There is no contemporary Western medicine to improve on the clinical outcome of conception in IVF-ET in women with low prognosis. Therefore, it is important to undertake a well-designed randomized trial to determine the effect of DKP in improving the clinical outcome of the conception of IVF-ET in women with low prognosis.

Trial registration
Chinese Clinical Trial Registry (ChiCTR). Trial registration number: ChiCTR1900026614. Registered on 16 October 2019.
Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism
Authors: Breen Michael S. , Browne Andrew , Hoffman Gabriel E. , Stathopoulos Sofia , Brennand Kristen , Buxbaum Joseph D. , Drapeau Elodie 
Published: June 2020

Abstract
Background
Phelan-McDermid syndrome (PMS) is a rare genetic disorder with high risk of autism spectrum disorder (ASD), intellectual disability, and language delay, and is caused by 22q13.3 deletions or mutations in the SHANK3 gene. To date, the molecular and pathway changes resulting from SHANK3 haploinsufficiency in PMS remain poorly understood. Uncovering these mechanisms is critical for understanding pathobiology of PMS and, ultimately, for the development of new therapeutic interventions.

Methods
We developed human-induced pluripotent stem cell (hiPSC)-based models of PMS by reprogramming peripheral blood samples from individuals with PMS (n = 7) and their unaffected siblings (n = 6). For each participant, up to three hiPSC clones were generated and differentiated into induced neural progenitor cells (hiPSC-NPCs; n = 39) and induced forebrain neurons (hiPSC-neurons; n = 41). Genome-wide RNA-sequencing was applied to explore transcriptional differences between PMS probands and unaffected siblings.

Results
Transcriptome analyses identified 391 differentially expressed genes (DEGs) in hiPSC-NPCs and 82 DEGs in hiPSC-neurons, when comparing cells from PMS probands and unaffected siblings (FDR < 5%). Genes under-expressed in PMS were implicated in Wnt signaling, embryonic development, and protein translation, while over-expressed genes were enriched for pre- and postsynaptic density genes, regulation of synaptic plasticity, and G-protein-gated potassium channel activity. Gene co-expression network analysis identified two modules in hiPSC-neurons that were over-expressed in PMS, implicating postsynaptic signaling and GDP binding, and both modules harbored a significant enrichment of genetic risk loci for developmental delay and intellectual disability. Finally, PMS-associated genes were integrated with other ASD hiPSC transcriptome findings and several points of convergence were identified, indicating altered Wnt signaling and extracellular matrix.

Limitations
Given the rarity of the condition, we could not carry out experimental validation in independent biological samples. In addition, functional and morphological phenotypes caused by loss of SHANK3 were not characterized here.

Conclusions
This is the largest human neural sample analyzed in PMS. Genome-wide RNA-sequencing in hiPSC-derived neural cells from individuals with PMS revealed both shared and distinct transcriptional signatures across hiPSC-NPCs and hiPSC-neurons, including many genes implicated in risk for ASD, as well as specific neurobiological pathways, including the Wnt pathway.
Genome engineering of induced pluripotent stem cells to manufacture natural killer cell therapies
Authors: Shankar Keerthana , Capitini Christian M. , Saha Krishanu 
Published: June 2020

AbstractNatural killer (NK) cells play a crucial role in host immunity by detecting cells that downregulate MHC class I presentation and upregulate stress ligands, as commonly seen in cancers. Current NK therapies using primary NK cells are prone to manufacturing issues related to expansion and storage. Alternative cell sources utilizing immortalized NK cell lines require irradiation and are dependent on systemic IL-2 administration, which has been associated with adverse effects. In contrast, NK cells differentiated from induced pluripotent stem cells (iPSC-NK cells) offer an off-the-shelf alternative that may overcome these bottlenecks. The development of a serum-free and feeder-free differentiation protocol allows for the manufacturing of clinically adaptable iPSC-NK cells that are equally as effective as primary NK cells and the NK-92 cell line for many indications. Moreover, genetic modifications targeting NK-mediated antibody-dependent cellular cytotoxicity capabilities, cytotoxicity, and checkpoint inhibitors may increase the therapeutic potential of iPSC-NK products. This review will highlight the current sources for NK therapies and their respective constraints, discuss recent developments in the manufacturing and genetic engineering of iPSC-NK cells, and provide an overview of ongoing clinical trials using NK cells.
Solutions of two fractional q-integro-differential equations under sum and integral boundary value conditions on a time scale
Authors: Alzabut Jehad , Mohammadaliee Behnam , Samei Mohammad Esmael 
Published: June 2020

AbstractIn this manuscript, by using the Caputo and Riemann–Liouville type fractionalq-derivatives, we consider two fractionalq-integro-differential equations of the forms${}^{c}\mathcal{D}_{q}^{\alpha }[x](t) + w_{1} (t, x(t), \varphi (x(t)) )=0$Dqαc[x](t)+w1(t,x(t),φ(x(t)))=0and$$ {}^{c}\mathcal{D}_{q}^{\alpha }[x](t) = w_{2} \biggl( t, x(t), \int _{0}^{t} x(r) \,\mathrm{d}r, {}^{c} \mathcal{D}_{q}^{\alpha }[x](t) \biggr) $$Dqαc[x](t)=w2(t,x(t),∫0tx(r)dr,cDqα[x](t))for$t \in [0,l]$t∈[0,l]under sum and integral boundary value conditions on a time scale$\mathbb{T}_{t_{0}}= \{ t: t =t_{0}q^{n}\}\cup \{0\}$Tt0={t:t=t0qn}∪{0}for$n\in \mathbb{N}$n∈Nwhere$t_{0} \in \mathbb{R}$t0∈Randqin$(0,1)$(0,1). By employing the Banach contraction principle, sufficient conditions are established to ensure the existence of solutions for the addressed equations. Examples involving algorithms and illustrated graphs are presented to demonstrate the validity of our theoretical findings.
Acute myocardial infarction in patient without cardiac risk factors during emergence from general anesthesia: a case report
Authors: Dang Thu Nguyen , Hoai Nam Tran , Viet Son Nguyen , Le Huu Tri , Van Khuong Truong , Manh Cuong Nguyen , Dac Tiep Tran 
Published: June 2020

Abstract
Background
Perioperative myocardial infarction is a rare but highly fatal complication, which often occurs in patients with poor preoperative cardiac conditions undergoing high-risk surgery. We report a case of acute myocardial infarction in a patient without cardiac risk factors during emergence from general anesthesia for removal of spinal screws.

Case presentation
A 37-year-old, 60 kg, and 160 cm man, who had no history of cardiovascular diseases, underwent removal of loosen spinal plug screws at L4-L5. The preoperative investigations revealed no abnormality and the patient was ASA I. The surgery was uneventful. During aspiration of the endotracheal tube, the patient suddenly experienced paroxysmal atrial fibrillation and ST segment elevation in DII lead. He was treated with oxygenation, optimal hemodynamics, minimize cardiac work, antiarrhythmias, and anticoagulation. The clinical conditions improved. Sinus rhythm was regained after 24 h and discharged without complications.

Conclusions
Myocardial infarction can occur suddenly and unexpectedly in patients without risk factors after a low-risk surgery in any period of general anesthesia. Close monitoring and prompt treatment with this condition is important for improving outcomes.
Efficacy of the green lace wing, Chrysoperla zastrowi sillemi (Esben-Peterson) (Neuroptera: Chrysopidae), against sucking pests of tomato: an appraisal under protected conditions
Authors: Nair Indu J. , Sharma Sudhendu , Kaur Rabinder 
Published: June 2020

AbstractPest infestations in net-houses are not sometimes different from that under open-field conditions, necessitating usage of pesticides. To examine the hypothesis that bioagents may have more potential under restricted plant growing conditions, the predatory potential of green lace wing,Chrysoperla zastrowi sillemiEsben-Peterson (Neuroptera: Chrysopidae) was evaluated against the sucking pests of tomato under screen-house conditions. The rates of release were fixed as 4, 5, and 6 s instar grubs plant−1and a total of 3 releases were made at 7 days interval, with first release at appearance of the aphid,Myzus persicae(Sulzer) and whitefly,Bemisia tabaci(Gennadius). The pooled data for the years 2018 and 2019 revealed that, the release rates 4, 5, and 6 grubs plant−1were not statistically different in reducing the population of these pests. The factorial analysis based on the release rate and time of these releases suggested that single release ofC.zastrowi sillemiat 4 grubs plant−1was effective against sucking pests in tomato grown under screen-house conditions.
Hot stage microscopy and its applications in pharmaceutical characterization
Authors: Kumar Arun , Singh Pritam , Nanda Arun 
Published: June 2020

AbstractHot stage microscopy (HSM) is a thermal analysis technique that combines the best properties of thermal analysis and microscopy. HSM is rapidly gaining interest in pharmaceuticals as well as in other fields as a regular characterization technique. In pharmaceuticals HSM is used to support differential scanning calorimetry (DSC) and thermo-gravimetric analysis (TGA) observations and to detect small changes in the sample that may be missed by DSC and TGA during a thermal experiment. Study of various physical and chemical properties such sample morphology, crystalline nature, polymorphism, desolvation, miscibility, melting, solid state transitions and incompatibility between various pharmaceutical compounds can be carried out using HSM. HSM is also widely used to screen cocrystals, excipients and polymers for solid dispersions. With the advancements in research methodologies, it is now possible to use HSM in conjunction with other characterization techniques such as Fourier transform infrared spectroscopy (FTIR), DSC, Raman spectroscopy, scanning electron microscopy (SEM) which may have additional benefits over traditional characterization techniques for rapid and comprehensive solid state characterization.
Azimuthal P-P prestack amplitudes in the presence of oil-filled aligned porosity (fracture porosity)
Authors: Lynn Heloise Bloxsom , Goodway Bill 
Published: June 2020

A 3D P-P high-fold full-azimuth full-offset reflection survey was acquired and processed to characterize a naturally fractured carbonate reservoir. The reservoir is a thick carbonate, which will flow commercial oil with a sufficient fracture network. Extensive calibration data include (1) a horizontal borehole’s resistivity image log, (2) the first 24 months cumulative oil produced, by stage, as known from chemical frac tracer data, (3) pre- and postfrac job instantaneous shut-in pressures, (4) microseismic, and (5) wireline log data. We used the cumulative oil production to document the spatially varying amount of aligned vertical porosity (aligned compliance or fracture porosity) connected to the stage borehole location. The stages of high oil production exhibited, for the fracture-perpendicular azimuth, the more positive amplitude variation with angle (AVA) gradients, and dimmer near-angle (6°–15° angles of incidence) amplitudes, compared to the fracture-parallel azimuth. The azimuthal variation of the AVA gradient fit the cos 2θ curve well, indicating the presence of one set of vertical aligned fractures dominating the azimuthal amplitude signature. In a similar fashion, the azimuthal variation of the mathematical intercept, physically the near-angle amplitudes, also fit the cos 2θ curve well. We have constructed crossplots of the azimuthal near-angle amplitude versus the AVA gradient on a bin-by-bin basis: we observed a straight line at bins with elevated oil production (elevated fracture density). A straight line crossplot of the (AVA gradient, mathematical intercept) is the signature of change of the (sensed) porosity, as long as the lithology and pore fluid are held constant. In accord with industry knowledge, we found that porosity affects the P impedance and thus the near-angle amplitudes: the aligned porosity yields azimuthal P impedance (measured at the 6°–15° angles of incidence). Legacy high-fold 3D P-P surveys rich in the 6°–20° angles of incidence should be considered for reprocessing and reinterpretation using these techniques.
Comparison of performance of medical students between two teaching modalities “Flip the classroom” and traditional lectures: A single center educational interventional study
Authors: Taher Fadwa , Hafiz Bayan , Alnajjar Taghreed , Almehmadi Bayan , Besharah Bayan , Gari Abdulrahim , Katib Yasir 
Published: June 2020

Objectives: This study aims to compare the students’ performance in Obstetrics and Gynecology by using two teaching modalities, i.e., Flip the classroom (FTC) compared to Traditional lectures (TL) among final year medical students and assessment of the students’ satisfaction towards FTC as learning modality.
Methods: An educational interventional study was conducted on 136 females final year medical students at Umm Al-Qura University, Makkah, Saudi Arabia from September to December; 2017. Out of 40 core topics of Obstetrics and Gynecology, eight were chosen for FTC and eight for TL. The performance in each teaching modality was assessed by comparing the score of the students in multiple choice question (MCQ) and objective structured clinical examination (OSCE) in the final examination. The final performance was compared between the FTC and TL selected topics. The data was analyzed by using SPSS version 16 (SPSS Inc., Chicago, IL, USA).
Results: MCQ and OSCE grades of students (n=136) were significantly higher in FTC versus TL topics, i.e., mean ± standard deviation (13.4 ± 2.7 vs. 12.3 ± 2.4; p < 0.001) and (33.9 ± 4.3 vs. 30.4 ± 4.7; p < 0.001), respectively. Almost 60% of the students expressed their satisfaction with FTC modality.
Conclusion: Scores were significantly high for Flip the classroom topics compared to Traditional lectures.
doi: https://doi.org/10.12669/pjms.36.5.2730
How to cite this:Tahir F, Hafiz B, Alnajjar T, Almehmadi B, Besharah B, Gari A, et al. Comparison of performance of medical students between two teaching modalities “Flip the classroom” and traditional lectures: A single center educational interventional study. Pak J Med Sci. 2020;36(5):958-964. doi: https://doi.org/10.12669/pjms.36.5.2730
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.