bluuebunny/crossref_metadata_2025_split huggingface dataset:
SMAD4 Gene Mutation Renders Pancreatic Cancer Resistance to Radiotherapy through Promotion of Autophagy
Authors: Wang Feng , Xia Xiaojun , Yang Chunying , Shen Jianliang , Mai Junhua , Kim Han-Cheon , Kirui Dickson , Kang Ya'an , Fleming Jason B. , Koay Eugene J. , Mitra Sankar , Ferrari Mauro , Shen Haifa 
Published: March 2018

Abstract
Purpose: Understanding the mechanism of radioresistance could help develop strategies to improve therapeutic response of patients with PDAC. The SMAD4 gene is frequently mutated in pancreatic cancer. In this study, we investigated the role of SMAD4 deficiency in pancreatic cancer cells' response to radiotherapy.
Experimental Design: We downregulated SMAD4 expression with SMAD4 siRNA or SMAD4 shRNA and overexpressed SMAD4 in SMAD4 mutant pancreatic cancer cells followed by clonogenic survival assay to evaluate their effects on cell radioresistance. To study the mechanism of radioresistance, the effects of SMAD4 loss on reactive oxygen species (ROS) and autophagy were determined by flow cytometry and immunoblot analysis, respectively. Furthermore, we measured radioresistance by clonogenic survival assay after treatment with autophagy inhibitor (Chloroquine) and ROS inhibitor (N-acetyl-l-cysteine) in SMAD4-depleted pancreatic cancer cells. Finally, the effects of SMAD4 on radioresistance were also confirmed in an orthotopic tumor model derived from SMAD4-depleted Panc-1 cells.
Results: SMAD4-depleted pancreatic cancer cells were more resistant to radiotherapy based on clonogenic survival assay. Overexpression of wild-type SMAD4 in SMAD4-mutant cells rescued their radiosensitivity. Radioresistance mediated by SMAD4 depletion was associated with persistently higher levels of ROS and radiation-induced autophagy. Finally, SMAD4 depletion induced in vivo radioresistance in Panc-1-derived orthotopic tumor model (P = 0.038). More interestingly, we observed that the protein level of SMAD4 is inversely correlated with autophagy in orthotopic tumor tissue samples.
Conclusions: Our results demonstrate that defective SMAD4 is responsible for radioresistance in pancreatic cancer through induction of ROS and increased level of radiation-induced autophagy. Clin Cancer Res; 24(13); 3176–85. ©2018 AACR.
A Review of Promising Natural Chemopreventive Agents for Head and Neck Cancer
Authors: Crooker Kyle , Aliani Rana , Ananth Megha , Arnold Levi , Anant Shrikant , Thomas Sufi Mary 
Published: March 2018

AbstractHead and neck squamous cell carcinoma (HNSCC) accounts for 300,000 deaths per year worldwide, and overall survival rates have shown little improvement over the past three decades. Current treatment methods including surgery, chemotherapy, and radiotherapy leave patients with secondary morbidities. Thus, treatment of HNSCC may benefit from exploration of natural compounds as chemopreventive agents. With excellent safety profiles, reduced toxicities, antioxidant properties, and general acceptance for use as dietary supplements, natural compounds are viewed as a desirable area of investigation for chemoprevention. Though most of the field is early in development, numerous studies display the potential utility of natural compounds against HNSCC. These compounds face additional challenges such as low bioavailability for systemic delivery, potential toxicities when consumed in pharmacologic doses, and acquired resistance. However, novel delivery vehicles and synthetic analogues have shown to overcome some of these challenges. This review covers 11 promising natural compounds in the chemoprevention of HNSCC including vitamin A, curcumin, isothiocyanate, green tea, luteolin, resveratrol, genistein, lycopene, bitter melon, withaferin A, and guggulsterone. The review discusses the therapeutic potential and associated challenges of these agents in the chemopreventive efforts against HNSCC. Cancer Prev Res; 11(8); 441–50. ©2018 AACR.
Evaluation of sample stability for a quantitative faecal immunochemical test and comparison of two sample collection approaches
Authors: Mellen Samantha , de Ferrars Maria , Chapman Claire , Bevan Sarah , Turvill James , Turnock Daniel 
Published: March 2018

Background Faecal immunochemical testing is increasingly being used to triage symptomatic patients for suspected colorectal cancer. However, there are limited data on the effect of preanalytical factors on faecal haemoglobin when measured by faecal immunochemical testing. The aim of this work was to evaluate the stability of faecal haemoglobin in faeces and to compare two methods of faecal haemoglobin sampling for faecal immunochemical testing. Methods Six patients provided faeces for faecal haemoglobin measurement which were transferred into specialized collection devices at baseline and at 1, 2, 3 and 7 days after storage at either room temperature or 4°C. A total of 137 patients returned both faeces transferred into the specialized collection device and faeces in a standard collection pot. A quantitative immunoturbidometric method was used to measure faecal haemoglobin and results were compared categorically. Discrepant results were assessed against diagnosis. Results Faecal haemoglobin concentration declined rapidly within a day of storage at room temperature but results remained ≥10 μg Hb/g faeces in 5/6 patients after two days. A faecal haemoglobin result ≥10 μg Hb/g faeces was obtained in 4/6 patients after storage for seven days at 4°C. Results obtained when patients used specialized collection devices were significantly different from results obtained when faeces was transferred into the specialized collection device in the laboratory. Conclusion There is considerable heterogeneity in the sample stability of faecal haemoglobin; therefore, samples should be transferred rapidly into specialized collection devices to prevent false-negative results. Use of collection devices by patients can lead to false-positive results compared with their use in a laboratory.
Development of a rapid liquid chromatography tandem mass spectrometry method for the quantitation of serum dexamethasone and its clinical verification
Authors: Hawley James M , Owen Laura J , Debono Miguel , Newell-Price John , Keevil Brian G 
Published: March 2018

Background Measurement of serum dexamethasone during the overnight dexamethasone-suppression test has been recommended to reduce false-positive results when investigating Cushing’s syndrome or increasingly commonly found adrenal incidentalomas. Despite this, there remains a paucity of well-validated dexamethasone methods currently available. Here, we describe the development of a rapid and sensitive liquid chromatography tandem mass spectrometry serum dexamethasone assay and verify its utility in a cohort of postmenopausal females. Method Isotopically labelled internal standard was added to samples prior to supported liquid extraction. Extracts were analysed using liquid chromatography tandem mass spectrometry in the positive electrospray ionization mode. Multiple reaction monitoring was used to detect dexamethasone and its corresponding internal standard transitions. Normal healthy postmenopausal women ( n = 95) were recruited and underwent an overnight dexamethasone suppression test, with serum dexamethasone and cortisol measurements at 09:00 after administration of oral dexamethasone 1 mg at 23:00 the night before. Results Mean intra- and inter-assay imprecision were 4.1% and 2.9%, respectively, for dexamethasone concentrations of 1.5, 6.0 and 12.0 nmol/L. Matrix effects were found to be negligible at 106–109% with recovery ranging from 96 to 100%. The limit of quantitation was 0.25 nmol/L, and structural analogue analysis proved the method to be robust against interferences. Applying a serum dexamethasone cut-off of >3.3 nmol/L was associated with a serum cortisol ≤50 nmol/L in 84/95 individuals. Conclusion We have developed a sensitive and robust liquid chromatography tandem mass spectrometry method for the quantitation of serum dexamethasone. The method can be used to identify false-positive results during the overnight dexamethasone suppression test or for pharmacokinetic studies.
Society and ‘good woman’: A critical review of gender difference in depression
Authors: Maji Sucharita 
Published: March 2018

Background: Worldwide, women are found to suffer from depression significantly more than men. This has puzzled the scientists since no biological explanation can completely resolve the matter. Method: Extant empirical work has been conducted to solve the mystery of the issue. However, most of the research has pivoted their attention to biology. Therefore, based on the previous literature from the disciplines of medicine, psychology and sociology, the author aimed at looking and reviewing the matter critically. Specifically, the present critical review aims at conceptualising the psychological, social and cultural factors in the context of gender difference in depression. Discussion: The work reveals that psychological variables such as women’s unique attachment patterns, relational self-construal, as well as a macro-level issue like power dynamics based on gender, and the skewed division of labour play an important role in gender difference in depression. The work also suggests that focusing solely on biological underpinnings may result in losing the entire scenario; therefore, social and cultural issues that place women in a socially disadvantaged position are equally important.
Nonsurgical Treatments of Patellar Tendinopathy: Multiple Injections of Platelet-Rich Plasma Are a Suitable Option: A Systematic Review and Meta-analysis
Authors: Andriolo Luca , Altamura Sante Alessandro , Reale Davide , Candrian Christian , Zaffagnini Stefano , Filardo Giuseppe 
Published: March 2018

Background: Patellar tendinopathy is a condition characterized by anterior knee activity–related pain. It has a high incidence among athletes engaged in jumping sports and may become a chronic condition. Nonoperative management is the first choice in these patients, and several nonsurgical treatment options have been proposed. Nonetheless, clear indications on the most effective approach to address patellar tendinopathy are still lacking. Purpose: To analyze the evidence on nonoperative options to treat chronic patellar tendinopathy through a systematic review of the literature and to perform a meta-analysis to identify the most effective nonsurgical option. Study Design: Systematic review and meta-analysis. Methods: The search was conducted with the PubMed and Cochrane databases on January 4, 2017. All clinical English-language reports of any level of evidence on nonsurgical treatment of patellar tendinopathy were included. The quality of each article was assessed by use of the Coleman score. A meta-analysis was performed on all articles reporting the Victorian Institute of Sport Assessment scale for patellar tendinopathy to evaluate the results of the most described treatments. Results: A total of 70 studies involving 2530 patients were included in the qualitative data synthesis. The Coleman score showed an overall poor study quality. The most described treatment groups that could be included in the meta-analysis were reported in 22 studies on eccentric exercise, extracorporeal shockwave therapy (ESWT), and platelet-rich plasma (PRP). Single and multiple PRP injections were evaluated separately. Eccentric exercise therapies obtained the best results ( P < .05) at short-term (<6 months, mean 2.7 ± 0.7 months). However, multiple injections of PRP obtained the best results ( P < .05), followed by ESWT and eccentric exercise, at long-term follow-up (≥6 months, mean 15.1 ± 11.3 months). Conclusion: The literature documents several nonsurgical approaches for the treatment of chronic patellar tendinopathy with important limitations in terms of study quality. The available evidence showed an overall positive outcome, but some differences have been highlighted. Eccentric exercises may seem the strategy of choice in the short-term, but multiple PRP injections may offer more satisfactory results at long-term follow-up and can be therefore considered a suitable option for the treatment of patellar tendinopathy.
Performance and Return to Sport After Tommy John Surgery Among Major League Baseball Position Players
Authors: Jack Robert A. , Burn Matthew B. , Sochacki Kyle R. , McCulloch Patrick C. , Lintner David M. , Harris Joshua D. 
Published: March 2018

Background: The anterior bundle of the medial ulnar collateral ligament (UCL) is the primary restraint to valgus stress at the elbow and is often injured among overhead throwing athletes. Despite prevention strategies, injuries to the elbow UCL are on the rise. Purpose: To determine (1) the return-to-sport (RTS) rate of Major League Baseball (MLB) position players after elbow medial UCL reconstruction, (2) postoperative career length and games per season, (3) pre- and postoperative performance, (4) postoperative performance versus matched control players, and (5) whether position players changed positions after UCL reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: MLB players who underwent elbow UCL reconstruction were identified (cases). Demographic and performance data were collected for each player. Matched controls were identified. RTS in MLB was defined as playing in at least 1 MLB game after UCL reconstruction. Comparisons between case and control groups and pre- and postoperative time points were made via paired samples Student t tests. Results: Thirty-three players (34 surgical procedures) were identified with a mean ± SD age of 30.2 ± 4.2 years and a mean experience in the MLB of 6.3 ± 3.9 years at the time of surgery. Twenty-eight players (84.8%) were able to RTS in MLB at a mean 336.9 ± 121.8 days. However, players ≥30 years old demonstrated a significantly lower RTS rate (53.3%) than players <30 years old (89.4%; P < .05). Catchers had a significantly shorter postoperative career length (2.8 ± 1.8 years) versus matched controls (6.1 ± 1.9 years; P < .05). Outfielders had a significantly lower wins above replacement postoperatively (0.8 ± 0.7) versus preoperatively (1.5 ± 1.1; P < .05). There were no performance differences between cases and matched controls. Twelve players (48%) returned to a different position postoperatively. Conclusion: The RTS rate for MLB position players after elbow UCL reconstruction is similar to that of pitchers. Catchers had a significantly shorter career length than that of matched controls. Outfielders performed worse postoperatively versus preoperatively. There is a high rate of position change after Tommy John surgery for infielders and outfielders.
Chemical Contaminants in Raw and Pasteurized Human Milk
Authors: Hartle Jennifer C. , Cohen Ronald S. , Sakamoto Pauline , Barr Dana Boyd , Carmichael Suzan L. 
Published: March 2018

Background: Environmental contaminants ranging from legacy chemicals like p,p’-dichlorodiphenyltrichloroethane (DDT) to emerging chemicals like phthalates are ubiquitous. Research aims/questions: This research aims to examine the presence and co-occurrence of contaminants in human milk and effects of pasteurization on human milk chemical contaminants. Methods: We analyzed human milk donated by 21 women to a milk bank for 23 chemicals, including the persistent organic pollutants (POPs) polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE) isomers that are known to sequester in adipose tissue, along with the current-use and nonpersistent pesticides chlorpyrifos and permethrin, phthalates, and bisphenol A (BPA). Human milk was analyzed raw and pasteurized for these chemicals using gas chromatography–tandem mass spectrometry for the POPs and high-performance liquid chromatography–tandem mass spectrometry for non-POPs. Results: Within the different chemical classes, PBDE47, PCB153, ppDDE, and MEHHP (phthalate metabolite) had the highest median concentrations and were observed in all samples. We also observed chlorpyrifos and BPA in all samples and permethrin in 90% of the samples tested. Only two chemicals, chlorpyrifos and permethrin, were susceptible to substantial degradation from pasteurization, a standard method for processing donated human milk. Conclusion: We detected 19 of 23 chemicals in all of our prepasteurized milk and 18 of 23 chemicals in all of our pasteurized milk. Pasteurization did not affect the presence of most of the chemicals. Future research should continue to explore human milk for potential chemical contamination and as a means to surveil exposures among women and children.
Effect of Ankle Position on Tibiotalar Motion With Screw Fixation of the Distal Tibiofibular Syndesmosis in a Fracture Model
Authors: Pallis Mark P. , Pressman David N. , Heida Kenneth , Nicholson Tyler , Ishikawa Susan 
Published: March 2018

Background: Anatomic reduction and fixation of the syndesmosis in traumatic injuries is paramount in restoring function of the tibiotalar joint. While overcompression is a potential error, recent work has called into question whether ankle position during fixation really matters in this regard. Our study aimed to corroborate more recent findings using a fracture model that, to our knowledge, has not been previously tested. Methods: Twenty cadaver leg specimens were obtained and prepared. Each was tested for tibiotalar motion under various conditions: intact syndesmosis, intact syndesmosis with lag screw compression, pronation external rotation type 4 (PER-4) ankle fracture with syndesmotic disruption, and single-screw syndesmotic fixation followed by plate and screw fracture and syndesmotic screw fixation. In each situation, the ankle was held in alternating plantarflexion and dorsiflexion when inserting the syndesmotic screw with the subsequent amount of maximal dorsiflexion being recorded following hand-tight lag screw fixation. Results: While ankle range of motion increased significantly with creation of the PER-4 injury, under no condition was there a statistically significant change in maximal dorsiflexion angle. Conclusion: Ankle position during distal tibiofibular syndesmosis fixation did not limit dorsiflexion of the ankle joint. Clinical Relevance: Our findings suggest that maximal dorsiflexion during syndesmotic screw fixation may not be necessary.
Comparison of Plantar Fasciitis Injected With Platelet-Rich Plasma vs Corticosteroids
Authors: Jain Sumit Kumar , Suprashant Kumar , Kumar Sanjeev , Yadav Arun , Kearns Stephen R. 
Published: March 2018

Background: Plantar fasciitis is one of the most common causes of heel pain. This prospective study compared the efficacy of local injection of corticosteroids vs platelet-rich plasma (PRP) in the treatment of plantar fasciitis. Methods: Patients were randomly allocated into 2 groups of 40 each (group A and group B). Patients were treated with local corticosteroid injection in group A and autologous PRP injection in group B. Clinical assessment was done prior to the injection and at 1 month, 3 months, and 6 months following the injection, which included visual analog pain scale, subjective rating using the modified Roles and Maudsley score, functional outcome score by the Foot and Ankle Outcome Instrument (FAI) core scale, and the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scale. Radiological assessment was done by measuring the thickness of the plantar fascia using ultrasonography. The mean age, sex, and body mass index of both groups were comparable. Results: Postinjection, there was significant improvement of visual analog score, modified Roles and Maudsley score, FAI core scale, AOFAS ankle-hindfoot score, and plantar fascia thickness in both the groups. However, with the numbers available, no significant difference in improvement could be detected between the above-mentioned variables in the 2 groups. Conclusion: We found that the treatment of plantar fasciitis with steroid or PRP injection was equally effective. Level of Evidence: Level II, prospective randomized comparative series.
The effect of bidialectalism on executive function
Authors: Poarch Gregory J , Vanhove Jan , Berthele Raphael 
Published: March 2018

Aims and objectives: We investigate how varying usage patterns in speakers of closely related language varieties might impact executive function. More specifically, bidialectals with more balanced usage were predicted to show better inhibitory control than less balanced bidialectals. Design: Thirty-four adult bidialectals of Standard German and Swabian German performed two executive function tasks (flanker and Simon). Data and analysis: The participants’ reaction times on the two executive function tasks were analysed using regression models. Data and R code are available online. Findings: Contrary to predictions, Swabian-dominant bidialectals showed smaller flanker and Simon effects than balanced German-Swabian bidialectals. Furthermore, contrary to some previous studies, executive function task performances correlated significantly. Originality: We discuss how bidialectal language usage patterns can be assessed and how arbitrary analytical decisions affect findings regarding the effects of bidialectalism on executive function. Significance: These findings shed a new light on the effects of bilingualism/bidialectalism on executive function.
The duration effect of head start enrolment on parents
Authors: Lee Kyunghee 
Published: March 2018

Summary In light of Head Start’s recent move toward longer program implementations, the current study examined whether the duration of Head Start enrollment impacts outcomes for parents: parental involvement in school, perceived helpfulness of social support, and use of formal social services. Findings Linear mixed model analyses examined whether parental outcomes differed depending on the number of years enrolled in Head Start. Parents whose child enrolled more years in Head Start were more likely to participate in their children’s schools and received more helpful social support than those whose child enrolled in fewer years of Head Start. No difference was found for formal social service use depending on longer duration of Head Start enrollment. Minority status, household risk factors, and non-English speaking were negatively associated with parental outcomes. Applications Early intervention programs, such as Head Start, should recruit eligible low-income families earlier for longer participation on family-focused programs.