bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revolutionizing the landscape of colorectal cancer treatment: The potential role of immune checkpoint inhibitors
Authors: Tolba Mai F. 
Published: May 2020

AbstractColorectal cancer (CRC) represents the third cause of cancer‐related mortalities worldwide. The progression of CRC to the metastatic phase significantly compromises the overall survival rates. Despite the advances in the therapeutic protocols, CRC treatment is still challenging. Cancer immunotherapy joined the ranks of surgery, chemotherapy, radiotherapy and targeted therapy as the fifth pillar in the foundation of cancer therapeutics. Interruption of the immunosuppressive signals within the tumor microenvironment and reactivation of antitumor immunity via targeting the molecular immune checkpoints generated promising therapeutic outcomes in several types of hard‐to‐treat cancers. The year 2017 witnessed the first US Food and Drug Administration (FDA) approval of immune checkpoint inhibitor (ICI) immunotherapy for the management of CRC. The approval was granted to pembrolizumab (anti‐PD‐1) for the treatment of patients with advanced/metastatic solid malignancies with mismatch‐repair deficiency including CRCs. Such natively immunogenic tumors constitute only a minor percentage of all CRCs. Therefore, it is imperative to utilize novel combinatorial regimens to enhance the response of a wider range of CRC tumors to cancer immunotherapy and help in extending the survival rates in patients with advanced/metastatic disease. This review highlights the novel approaches under clinical development to overcome the resistance of CRCs to immunotherapy and improve the therapeutic outcomes.
Cerebro‐placental ratio as a prognostic factor of fetal outcome in pregnancy complicated by maternal sickle cell disease
Authors: Swarray‐Deen Alim , Nkyekyer Kobinah , Seffah Joseph D. , Mumuni Kareem , Mensah‐Brown Shirley A. , Tuuli Methodius G. , Oppong Samuel A. 
Published: May 2020

AbstractObjectivesTo assess the role of the cerebro‐placental ratio (CPR) in predicting adverse fetal outcomes among women with sickle cell disease (SCD).MethodsA prospective cohort study at Korle‐Bu Teaching Hospital, Accra, Ghana, between January and June 2016. Pregnant women with SCD at 34 gestational weeks or more underwent weekly fetal umbilical and middle cerebral artery Doppler assessment until delivery. Participants were categorized into two study arms based on CPR (<1.1 or ≥1.1). The primary outcome, a composite of adverse perinatal outcomes including intrauterine growth restriction, stillbirth, low birthweight, and neonatal intensive care unit admission, was compared between groups.ResultsOverall, 48 pregnant women with SCD were enrolled, and 5 had a fetus with CPR less than 1.1. Low CPR (<1.1) had a sensitivity and specificity of 29.4% and 100%, respectively, for predicting composite adverse perinatal outcomes. Sensitivity and specificity were, respectively, 100% and 93.5% for predicting stillbirth, and 40.2% and 97.4% for predicting low birthweight. Perinatal outcomes did not differ between the two major sickle cell genotypes (hemoglobin SS and hemoglobin SC).ConclusionsAmong women with SCD, CPR less than 1.1 was associated with adverse perinatal outcomes, particularly low birthweight and stillbirth.
Ten‐year follow‐up study of long‐term outcomes after conservative surgery for early‐stage ovarian cancer
Authors: Bogani Giorgio , Ditto Antonino , Pinelli Ciro , Lopez Salvatore , Chiappa Valentina , Raspagliesi Francesco 
Published: May 2020

AbstractObjectiveTo evaluate long‐term outcomes after surgery for apparent early‐stage ovarian cancer (OC).MethodsRetrospective analysis of women who underwent staging surgery for apparent early‐stage OC at a single center in Milan, Italy, from 1990 to 2008, and had a follow‐up longer than 10 years (living women with no recurrence). Univariate and multivariate analyses and propensity score matching were carried out.ResultsOverall, 182 women underwent radical (n=148, 81.3%) or conservative (n=34, 18.7%) procedures for early‐stage OC. Ten‐year disease‐free and overall survival were 82.9% (n=151) and 87.9% (n=160), respectively. Conservative or radical surgery had similar disease‐free (log‐rank test, P=0.783) and overall (log‐rank test, P=0.783) survival. These data were confirmed after the application of propensity score matching. High‐risk features correlated with non‐significant worse disease‐free survival (P=0.080). In the high‐risk group (≥Grade 3 or ≥ Stage IC), type of surgical approach (conservative vs radical) did not affect survival (hazard ratio, 0.81; 95% confidence interval, 0.18–3.56; P=0.781).ConclusionWomen with early‐stage OC had encouraging long‐term survival. The presence of high‐risk disease had detrimental effects on survival, regardless of surgical approach. High‐risk disease should not be considered a contraindication to conservative surgery.
Upregulation of Toll‐like receptor 4 through anti‐miR‐Let‐7a enhances blastocyst attachment to endometrial cells in mice
Authors: Hosseini Sara , Hosseini Samaneh , Salehi Mohammad 
Published: May 2020

AbstractDespite encouraging advances in fertility technology, the success rate of an ongoing pregnancy is relatively low and predominantly associated with implantation failure. Inflammatory responses are beneficial in the fetomaternal interface and supposedly accelerate the chances for successful implantation. The current study aims to determine the effect of Toll‐like receptor 4 (TLR4) overexpression in mouse blastocysts via Let‐7a downregulation using intracytoplasmic sperm injection‐sperm‐mediated gene transfer on embryo attachment rate. The pLenti‐III‐GFP‐miR‐Off‐Let‐7a vector was transmitted to oocytes derived via in vitro maturation (IVM) and in vivo oocytes by using NaOH‐treated spermatozoa. Let‐7a and TLR4 expression levels were evaluated by quantitative real‐time polymerase chain reaction (qRT‐PCR), immunocytochemistry, and western blot analysis in both oocytes and embryos. Blastocyst adhesion on the endometrial cells was monitored by microscopic analysis. qRT‐PCR results showed that Let‐7a expression decreased in the IVM (GV‐MII) oocytes compared to the in vivo oocyte (MII) group (p < .05). TLR4 showed a higher expression in GV‐MII oocytes at both the gene and protein levels (p < .05). Following anti‐miR‐Let‐7a transmission, the TLR4 expression level was significantly upregulated in embryos compared with the control groups (p < .05). Attachment and migration of trophoblasts cells towards endometrial cells dramatically increased compared to the control group (p < .05). Based on our results, we concluded that Let‐7a might mediate embryo attachment through regulation of TLR4 expression levels.
Huntington's Disease Progression: A Population Modeling Approach to Characterization Using Clinical Rating Scales
Authors: Sun Wan , Zhou Di , Warner John H. , Langbehn Douglas R. , Hochhaus Guenther , Wang Yaning 
Published: May 2020

AbstractDevelopment of effective therapeutics that slow Huntington's disease progression is a research priority that requires an understanding of natural disease progression. We applied a population‐modeling approach to describe the progression of 2 routinely used rating scales — the total motor score and the total functional capacity score. Models were fitted to data from research participants aged ≥ 18 years with Huntington's disease stage I or II at study entry (total functional capacity score ≥ 7), from a controlled clinical trial (CARE‐HD) and 2 observational studies (COHORT and Registry). A logistic model without shape factors was selected as the base model based on placebo data from CARE‐HD and validated using data from the CARE‐HD active‐treatment arms. Albeit with a smaller progression rate constant than was found in CARE‐HD, the proposed models provided reasonable predictions for both rating scales in the pooled data from COHORT and Registry and were considered suitable for use in clinical trial simulations. Results also showed that disease burden score (a product of age and expanded CAG length) is a significant covariate on both the progression rate constant and the baseline score in the total motor score model. These findings suggest that total motor score and total functional capacity progress fastest near their half‐maximal score, implying that the efficiency of clinical trials evaluating disease‐modifying therapeutics for Huntington's disease could be enhanced by enrolling patients with faster disease progression or evaluating treatment effect near their half‐maximal score, provided that the evaluated therapy is expected to be efficacious at this disease stage.
Cortical motor areas show different reorganizational changes in adult patients with brachial plexus birth injury (BPBI)
Authors: Tuna Zeynep , Oskay Deran , Algin Oktay , Koçak Orhan Murat 
Published: May 2020

AbstractIntroductionBrachial plexus birth injury (BPBI) may cause permanent disability. It is recently thought to result from the (mal)adaptive reorganizational central nervous system problems.MethodsIn this study, adult patients with BPBI and age‐matched healthy controls were compared for the cortical activity during action observation by functional magnetic resonance imaging (fMRI).ResultsThe cortical activity in patients was significantly weaker than in the control group (p < .05). Areas of difference were middle temporal gyrus, premotor area, and inferior parietal lobule. The signal change in these areas was significantly lower in the patient group (p < .05).ConclusionsThis study showed that the cortical activity in the associative motor regions was weaker in the patients while no primary region showed any difference. The results were concluded that there is a diversity in the neuroplastic changes between primary and associative motor areas. Clinically, neurorehabilitative interventions should be planned based on this diversity.
Composition and chemical properties of the soils of the city of Santiago de Compostela, northwestern Spain
Authors: Paradelo Remigio , Herbón Cecilia , Barral María Teresa 
Published: May 2020

AbstractUrban soils are still insufficiently studied despite the relevance of their functions in the urban environment. The city of Santiago de Compostela (northwestern Spain) offers interesting opportunities for the study of urban soils because of its geological diversity and the variety of land use and vegetation. With the objective of increasing information about urban soils in Spain, we studied samples from 56 urban soils (0–20 cm) in this city, developed over different parent materials (granites, gneiss, schists, and amphibolites) and under several land uses (lawn areas, forested areas, urban allotment gardens, peri‐urban agricultural soils, and a green roof). The main physicochemical properties of the soils were analyzed, including bulk density, texture, pH, organic matter, cation exchange capacity, available P, and compounds of Fe and Al. The soils are coarse textured (dominant texture is sandy loam) and acidic (pH in water from 4.7 to 6.9), with moderate to high organic matter contents (13–137 g organic C kg−1). Cation exchange capacity ranges from 9 to 48 cmolc kg−1, with Ca as the most abundant exchangeable cation in most soils. Overall, the soils do not show several of the common features of other urban soils, such as alkalinity, high bulk density, or large amounts of artifacts, and their composition is very similar to their natural counterparts in the region. The conservation of these soils with a low degree of artificialization is essential because they can provide a wide range of ecosystem services.
p.Cys223Tyr mutation causing Crigler–Najjar syndrome type II
Authors: Xiong Qing‐Fang , Zhou Hui , Yang Yong‐Feng 
Published: May 2020

AbstractCrigler–Najjar syndrome (CNs) is a rare hereditary unconjugated hyperbilirubinemia caused by mutations in the bilirubin Uridine (UDP) glucuronosyltransferase family 1 member A1 (UGT1A1, ENSG00000241635) gene. Two patients were clinically diagnosed with Crigler–Najjar Syndrome types II (CNs‐II) can be clinically diagnosed which were based on the level of total bilirubin, efficacy of phenobarbital treatment, normal liver architecture and exclusion of hemolysis. Diagnosis was also confirmed by UGT1A1 gene mutations, which by sequencing the coding region for UGT1A1 gene mutations, which were the homozygous mutations c.668G > A/p.Cys223Tyr and which caused less than 10% of activity of the enzyme. No data have been reported about this mutate in the population. These patients have a good prognosis and require no active intervention, indicating that an early accurate diagnosis is necessary for disease management and genetic counseling.
Rectal stenosis due to solitary pelvic recurrence of hilar cholangiocarcinoma
Authors: Shioi Ikuma , Yamaoka Yusuke , Shiomi Akio , Kagawa Hiroyasu , Hino Hitoshi , Manabe Shoichi , Aizawa Daisuke 
Published: May 2020

AbstractAn 85‐year‐old woman was admitted to a hospital with abdominal pain. Five years prior to admission, she had a history of hilar cholangiocarcinoma of pStage IIIC. Contrast‐enhanced computed tomography showed a mass between the rectum and uterus as well as bowel obstruction due to the lesion. Colonoscopy showed severe stenosis at the lower rectum and elevation of the submucosal layer with linear erosion. Rectal cancer was suspected, and pelvic recurrence of hilar cholangiocarcinoma or endometrial carcinoma infiltrating the rectum was considered as differential diagnosis. She underwent robot‐assisted low anterior resection combined with partial resection of the uterus. The immunohistopathological findings of the resected specimen favored a diagnosis of metastasis of cholangiocarcinoma, rather than primary rectal cancer or endometrial carcinoma. There were no signs of recurrence after 10 months of follow‐up. Hilar cholangiocarcinoma is a disease with poor prognosis. Recurrence is frequently experienced even after curative resection. Patients with recurrence are rarely candidates for re‐resection. However, better prognosis is reported for those with complete resection.
Evidence for independent peripheral and central age‐related hearing impairment
Authors: Bao Jianxin , Yu Yan , Li Hui , Hawks John , Szatkowski Grace , Dade Bethany , Wang Hao , Liu Peng , Brutnell Thomas , Spehar Brent , Tye‐Murray Nancy 
Published: May 2020

AbstractDeleterious age‐related changes in the central auditory nervous system have been referred to as central age‐related hearing impairment (ARHI) or central presbycusis. Central ARHI is often assumed to be the consequence of peripheral ARHI. However, it is possible that certain aspects of central ARHI are independent from peripheral ARHI. A confirmation of this possibility could lead to significant improvements in current rehabilitation practices. The major difficulty in addressing this issue arises from confounding factors, such as other age‐related changes in both the cochlea and central non‐auditory brain structures. Because gap detection is a common measure of central auditory temporal processing, and gap detection thresholds are less influenced by changes in other brain functions such as learning and memory, we investigated the potential relationship between age‐related peripheral hearing loss (i.e., audiograms) and age‐related changes in gap detection. Consistent with previous studies, a significant difference was found for gap detection thresholds between young and older adults. However, among older adults, no significant associations were observed between gap detection ability and several other independent variables including the pure tone audiogram average, the Wechsler Adult Intelligence Scale‐Vocabulary score, gender, and age. Statistical analyses showed little or no contributions from these independent variables to gap detection thresholds. Thus, our data indicate that age‐related decline in central temporal processing is largely independent of peripheral ARHI.
Dispersive solid‐phase extraction of buprenorphine from biological fluids using metal‐organic frameworks and its determination by ultra‐performance liquid chromatography
Authors: Mohammadi Farzaneh , Shabani Ali Mohammad Haji , Dadfarnia Shayessteh , Ansari Mehdi , Asgharinezhad Ali Akbar 
Published: May 2020

AbstractIn this work, various types of metal‐organic frameworks were synthesized, and their affinities toward buprenorphine were evaluated using dispersive solid‐phase extraction. The extracted buprenorphine was determined by ultra high performance liquid chromatography‐ultraviolet detection system. The highest extraction recovery was observed by employing zeolitic imidazole framework‐67. Then, a facile and fast extraction method was designed for the extraction and purification of the target drug. Optimization of the extraction method was carried out by the design of experiment approach. A linearity range of 1–1000 μg/L with the limit of detection of 0.15 μg/L and relative standard deviations (50 μg/L, n = 5) of 3.4% was obtained for standard sample analysis. Under optimized experimental and instrumental conditions, the relative recoveries were in the range of 95 to 111%. Eventually, zeolitic imidazole framework‐67 was successfully employed for the extraction and determination of buprenorphine in the biological fluids with satisfactory results.
Evaluation of the Perinodular Stiffness Potentially Predicts the Malignancy of Thyroid Nodules
Authors: Hu Lei , He Nian An , Xie Li , Ye Xianjun , Liu Xiao , Pei Chong , Zhou Hang Cheng , Zhong Wen 
Published: May 2020

ObjectivesTo evaluate the surrounding tissue stiffness measured by sound touch elastography for differential diagnosis of thyroid nodules (TNs).MethodsThirty‐nine benign and 90 malignant TNs were included in this study. The conventional ultrasound features, the maximum Young modulus value of the stiffness of the TNs (recorded as E), and the stiffness of the 0.5‐, 1.0‐, 1.5‐, and 2.0‐mm perinodular regions of the TNs (recorded as Eshell0.5, Eshell1.0, Eshell1.5, and Eshell2.0, respectively) were prospectively analyzed and compared to histopathologic results. The abundance of collagen fibers at various widths in the perinodular regions of the TNs was evaluated by Masson staining and ImageJ software (National Institutes of Health, Bethesda, MD). The fibrous structures in the perinodular regions of the TNs were classified.ResultsThe various Eshell values of malignant TNs were significantly higher than those of benign TNs (P < .001 for all). Eshell0.5 correlated highly with E in the malignant TNs and in all samples (r = 0.722 and 0.772; P < .001 for both). Eshell2 yielded the highest area under the receiving operating characteristic curve value (0.96) for the differential diagnosis of TNs. The abundance of collagen fibers in the 2‐mm perinodular region of the TNs was closely correlated with Eshell2 in the malignant TNs and in all samples (r =0.729 and 0.867; P < .001). The Eshell2 values for different levels of disorder of the tissue surrounding TNs were significantly different (P < .01 for all).ConclusionsPerinodular stiffness measured by sound touch elastography improved the diagnostic accuracy in TNs.
One‐Size‐Fits‐All Approach Does Not Work for Gynecology Trainees Learning Endometriosis Ultrasound Skills
Authors: Leonardi Mathew , Ong Jozarino , Espada Mercedes , Stamatopoulos Nicole , Georgousopoulou Ekavi , Hudelist Gernot , Condous George 
Published: May 2020

ObjectivesTo evaluate whether gynecologic surgical trainees (fellows) can become competent in the real‐time classification of the pouch of Douglas (POD) obliteration state and direct visualization of bowel deep endometriosis (DE) during a program with a prespecified number of transvaginal ultrasound (TVUS) examinations.MethodsWe performed a prospective study between December 2017 and December 2018. Three fellows (F1–F3) performed 50 scans each, which were all supervised by an expert sonologist, who performed the reference standard TVUS examination. The fellows performed a focused TVUS examination to assess the bowel and POD state, having been blinded to the patient's clinical history and reference standard findings. Immediate feedback and hands‐on teaching were provided after each of the fellow's official classifications. To evaluate the number of scans needed to gain competency, the cumulative summation test for the learning curve was used.ResultsA total of 150 examinations were performed on 145 patients. Twenty‐six (17.9%) patients had a diagnosis of bowel DE, and 34 (23.4%) were classified as having a negative sliding sign by the reference standard. The overall accuracy of the presence/absence of bowel DE was 90% (range, 82%–94%). The overall accuracy of POD state classification was 93% (range, 90%–96%). The cumulative summation test for the learning curve for bowel DE showed that F1 did not reach competency by 50 scans, whereas F2 and F3 required 21 and 25 scans, respectively. For POD obliteration, F2 did not reach competency, whereas F1 and F3 required 40 and 22 scans.ConclusionsNot all trainees can reach competency for TVUS evaluations of POD obliteration and bowel DE in a predefined number of scans.
Age Is Associated With Pain Experience and Opioid Use After Head and Neck Free Flap Reconstruction
Authors: Rettig Eleni M. , Janus Jeffrey R. , Moore Eric J. , Price Daniel L. , Glasgow Amy E. , Marinelli John P. , Habermann Elizabeth B. , Van Abel Kathryn M. 
Published: May 2020

ObjectivesTo describe pain experience and opioid use after major head and neck reconstructive surgery.Study DesignRetrospective cohort study.MethodsPatients undergoing major head and neck surgery with microvascular free tissue transfer (free flaps) at a tertiary academic center were included. Pain scores (0–10) and demographic and clinical data were ascertained from medical records. Discharge opioid prescriptions and refills obtained within 30 days were recorded. Patient characteristics were compared with pain scores using nonparametric rank‐sum tests and with likelihood of refill using logistic regression models to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs).ResultsThe study population comprised 445 patients. Median age was 60 years (interquartile range 50–68). Most patients had cancer (N = 350, 78%). The majority of free flaps were fibula (N = 153, 34%) or radial forearm (N = 159, 36%). Older patients reported significantly lower pain scores, whereas patients with opioid tolerance, anxiety, current smokers, and those undergoing larger volume resections or boney free flaps reported significantly higher pain scores. One‐quarter (N = 115, 26%) of patients obtained opioid refills. Patients aged ≥ 60 years had one‐half the odds of obtaining a refill compared with patients aged < 60 years (adjusted odds ratio [aOR] = 0.52, 95% confidence interval [CI] = 0.33–0.84), whereas surgical defect volume ≥ 100 cm3 (aOR = 1.92, 95% CI = 1.21–3.07) and higher pain score (aOR = 1.19, 95% CI = 1.07–1.32 per 1 point increase) increased the odds of refill.ConclusionContinued opioid use after discharge is common among patients undergoing major head and neck reconstruction, particularly for younger patients and after more extensive surgery. Older patients reported lower pain intensity and were less likely to obtain opioid refills, highlighting the wisdom of judicious opioid use for this vulnerable population.Level of EvidenceIV Laryngoscope, 130: E469–E478, 2020