bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Trial of Cediranib in Combination With Cisplatin and Pemetrexed in Chemotherapy-Naïve Patients With Unresectable Malignant Pleural Mesothelioma (SWOG S0905)
Authors: Tsao Anne S. , Miao Jieling , Wistuba Ignacio I. , Vogelzang Nicholas J. , Heymach John V. , Fossella Frank V. , Lu Charles , Velasco Mario R. , Box-Noriega Brandy , Hueftle James G. , Gadgeel Shirish , Redman Mary W. , Gandara David R. , Kelly Karen 
Published: August 2019

PURPOSE Antiangiogenic agents combined with chemotherapy have efficacy in the treatment of unresectable malignant pleural mesothelioma (MPM). Cediranib (AstraZeneca, Cheshire, United Kingdom), a vascular endothelial growth factor receptor and platelet-derived growth factor receptor inhibitor, demonstrated therapeutic potential in a prior phase I trial. We evaluated a phase II trial for efficacy. PATIENTS AND METHODS SWOG S0905 (ClinicalTrials.gov identifier: NCT01064648 ) randomly assigned cediranib or placebo with platinum-pemetrexed for six cycles followed by maintenance cediranib or placebo in unresectable chemotherapy-naïve patients with MPM of any histologic subtype. Primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 progression-free survival (PFS). Secondary end points included overall survival, PFS by modified RECIST v1.1, response (modified RECIST and RECIST v1.1), disease control, and safety/toxicity. The trial was designed to detect a difference in RECIST v1.1 PFS at the one-sided 0.1 level using a stratified log-rank test. RESULTS Ninety-two eligible patients were enrolled (75% epithelioid and 25% biphasic or sarcomatoid). The cediranib arm had more grade 3 and 4 diarrhea, dehydration, hypertension, and weight loss. Cediranib improved PFS by RECIST v1.1 (hazard ratio, 0.71; 80% CI, 0.54 to 0.95; P = .062; 7.2 months v 5.6 months) and increased modified RECIST v1.1 response (50% v 20%; P = .006). By modified RECIST v1.1, cediranib numerically increased PFS (hazard ratio, 0.77; 80% CI, 0.59 to 1.02; P = .12; median, 6.9 months v 5.6 months). No significant difference in overall survival was observed. CONCLUSION The addition of cediranib to platinum-pemetrexed improved PFS by RECIST v1.1 and response rate by modified RECIST in patients with unresectable MPM. Whereas adding antiangiogenics to chemotherapy has been a successful strategy for some patients, the cediranib toxicity profile and small incremental survival benefit precludes additional development in MPM.
Maintaining Outstanding Outcomes Using Response- and Biology-Based Therapy for Intermediate-Risk Neuroblastoma: A Report From the Children’s Oncology Group Study ANBL0531
Authors: Twist Clare J. , Schmidt Mary Lou , Naranjo Arlene , London Wendy B. , Tenney Sheena C. , Marachelian Araz , Shimada Hiroyuki , Collins Margaret H. , Esiashvili Natia , Adkins E. Stanton , Mattei Peter , Handler Michael , Katzenstein Howard , Attiyeh Edward , Hogarty Michael D. , Gastier-Foster Julie , Wagner Elizabeth , Matthay Katherine K. , Park Julie R. , Maris John M. , Cohn Susan L. 
Published: August 2019

PURPOSE The primary objective of the Children’s Oncology Group study ANBL0531 (ClinicalTrials.gov identifier: NCT00499616 ) was to reduce therapy for subsets of patients with intermediate-risk neuroblastoma using a biology- and response-based algorithm to assign treatment duration while maintaining a 3-year overall survival (OS) of 95% or more for the entire cohort. PATIENTS AND METHODS Children younger than age 12 years with intermediate-risk stage 2A/2B or stage 3 tumors with favorable histology; infants younger than age 365 days with stage 3, 4 or 4S disease; and toddlers from 365 to younger than 547 days with favorable histology, hyperdiploid stage 4, or unfavorable histology stage 3 tumors were eligible. Patients with MYCN-amplified tumors were excluded. Patients were assigned to initially receive two (group 2), four (group 3), or eight (group 4) cycles of chemotherapy with or without surgery on the basis of prognostic markers, including allelic status of chromosomes 1p and 11q; ultimate duration of therapy was determined by overall response. RESULTS Between 2007 and 2011, 404 evaluable patients were enrolled. Compared with legacy Children’s Oncology Group studies, subsets of patients had a reduction in treatment. The 3-year event-free survival and OS rates were 83.2% (95% CI, 79.4% to 87.0%) and 94.9% (95% CI, 92.7% to 97.2%), respectively. Infants with stage 4 tumors with favorable biology (n = 61) had superior 3-year event-free survival compared with patients with one or more unfavorable biologic features (n = 47; 86.9% [95% CI, 78.3% to 95.4%] v 66.8% [95% CI, 53.1% to 80.6%]; P = .02), with a trend toward OS advantage (95.0% [95% CI, 89.5% to 100%] v 86.7% [95% CI, 76.6% to 96.7%], respectively; P = .08). OS for patients with localized disease was 100%. CONCLUSION Excellent survival was achieved with this treatment algorithm, with reduction of therapy for subsets of patients. More-effective treatment strategies still are needed for infants with unfavorable biology stage 4 disease.
Immune-Related Adverse Events Requiring Hospitalization: Spectrum of Toxicity, Treatment, and Outcomes
Authors: Balaji Aanika , Zhang Jiajia , Wills Beatriz , Marrone Kristen A. , Elmariah Hany , Yarchoan Mark , Zimmerman Jacquelyn W. , Hajjir Khalid , Venkatraman Deepti , Armstrong Deborah K. , Laheru Daniel A. , Mehra Ranee , Ho Won Jin , Reuss Joshua E. , Heng Joseph , Vellanki Paz , Donehower Ross C. , Holdhoff Matthias , Naidoo Jarushka 
Published: August 2019

PURPOSE: Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs). The proportion of patients who are hospitalized for irAEs and their spectrum, management, and outcomes are not well described. METHODS: We report the proportion of hospitalized patients in an academic center who were treated with ICIs from May to December 2017. Patient characteristics, toxicities, management, and outcomes for confirmed irAE admissions are reported. Associations between patient features and irAE hospitalizations are examined. RESULTS: Twenty-three percent (n = 100) of 443 patients who were admitted to an academic oncology center over 6 months had ever received ICIs. Of these patients, 41% were admitted for suspected irAEs and 23% were confirmed irAEs. IrAEs accounted for 5% of all oncology hospitalizations (n = 23). Ninety-one percent of patients with confirmed irAEs prompted a medicine subspecialist consultation, most commonly gastroenterology (22%). Fifteen patients (65%) had their irAEs improve/resolve, seven (30%) had worsening irAEs, and three (13%) died of their irAEs. The majority of patients (n = 20; 87%) discontinued ICIs after discharge. Among ICI-treated patients who required admission, an increased likelihood of irAE-related hospitalization was associated with patient age older than 65 years (odds ratio, 5.4; 95% CI, 1.6 to 17.8) and receipt of combination immunotherapy (OR, 6.8; 95% CI, 2.0 to 23.2). CONCLUSION: A notable proportion of ICI-treated patients are hospitalized for irAEs, and these patients have a high demand for multidisciplinary management. Older age and combination ICI treatment were associated with an increased risk of irAE-related hospitalization. Whereas these data are from an academic center and include patients in clinical trials, with expanding use of ICIs, these data have important implications for inpatient service planning and risk stratification.
The zebrafish subcortical social brain as a model for studying social behavior disorders
Authors: Geng Yijie , Peterson Randall T. 
Published: August 2019

ABSTRACT
Social behaviors are essential for the survival and reproduction of social species. Many, if not most, neuropsychiatric disorders in humans are either associated with underlying social deficits or are accompanied by social dysfunctions. Traditionally, rodent models have been used to model these behavioral impairments. However, rodent assays are often difficult to scale up and adapt to high-throughput formats, which severely limits their use for systems-level science. In recent years, an increasing number of studies have used zebrafish (Danio rerio) as a model system to study social behavior. These studies have demonstrated clear potential in overcoming some of the limitations of rodent models. In this Review, we explore the evolutionary conservation of a subcortical social brain between teleosts and mammals as the biological basis for using zebrafish to model human social behavior disorders, while summarizing relevant experimental tools and assays. We then discuss the recent advances gleaned from zebrafish social behavior assays, the applications of these assays to studying related disorders, and the opportunities and challenges that lie ahead.
During Cycling What Limits Maximum Mechanical Power Output at Cadences above 120 rpm?
Authors: HODSON-TOLE EMMA F. , BLAKE OLLIE M. , WAKELING JAMES M. 
Published: August 2019

ABSTRACT

Purpose
A key determinant of muscle coordination and maximum power output during cycling is pedaling cadence. During cycling, the neuromuscular system may select from numerous solutions that solve the task demands while producing the same result. For more challenging tasks, fewer solutions will be available. Changes in the variability of individual muscle excitations (EMG) and multimuscle coordination, quantified by entropic half-life (EnHL), can reflect the number of solutions available at each system level. We, therefore, ask whether reduced variability in muscle coordination patterns occur at critical cadences and if they coincide with reduced variability in excitations of individual muscles.

Methods
Eleven trained cyclists completed an array of cadence–power output conditions. The EnHL of EMG intensity recorded from 10 leg muscles and EnHL of principal components describing muscle coordination were calculated. Multivariate adaptive regressive splines were used to determine the relationships between each EnHL and cycling condition or excitation characteristics (duration, duty cycle).

Results
Muscle coordination became more persistent at cadences up to 120 rpm, indicated by increasing EnHL values. Changes in EnHL at the level of the individual muscles differed from the changes in muscle coordination EnHL, with longer EnHL occurring at the slowest (<80 rpm) and fastest (>120 rpm) cadences. The EnHL of the main power producing muscles, however, reached a minimum by 80 rpm and did not change across the faster cadences studied.

Conclusions
Muscle coordination patterns, rather than the contribution of individual muscles, are key to power production at faster cadences in trained cyclists. Reductions in maximum power output at cadences above 120 rpm could be a function of the time available to coordinate orientation and transfer of forces to the pedals.
Response of Liver Metabolic Pathways to Ketogenic Diet and Exercise Are Not Additive
Authors: HUANG TAI-YU , GOLDSMITH FELICIA R. , FULLER SCOTT E. , SIMON JACOB , BATDORF HEIDI M. , SCOTT MATTHEW C. , ESSAJEE NABIL M. , BROWN JOHN M. , BURK DAVID H. , MORRISON CHRISTOPHER D. , BURKE SUSAN J. , COLLIER J. JASON , NOLAND ROBERT C. 
Published: August 2019

ABSTRACT

Purpose
Studies suggest ketogenic diets (KD) produce favorable outcomes (health and exercise performance); however, most rodent studies have used a low-protein KD, which does not reflect the normal- to high-protein KD used by humans. Liver has an important role in ketoadaptation due to its involvement in gluconeogenesis and ketogenesis. This study was designed to test the hypothesis that exercise training (ExTr) while consuming a normal-protein KD (NPKD) would induce additive/synergistic responses in liver metabolic pathways.

Methods
Lean, healthy male C57BL/6J mice were fed a low-fat control diet (15.9% kcal protein, 11.9% kcal fat, 72.2% kcal carbohydrate) or carbohydrate-deficient NPKD (16.1% protein, 83.9% kcal fat) for 6 wk. After 3 wk on the diet, half were subjected to 3-wk treadmill ExTr (5 d·wk−1, 60 min·d−1, moderate-vigorous intensity). Upon conclusion, metabolic and endocrine outcomes related to substrate metabolism were tested in liver and pancreas.

Results
NPKD-fed mice had higher circulating β-hydroxybutyrate and maintained glucose at rest and during exercise. Liver of NPKD-fed mice had lower pyruvate utilization and greater ketogenic potential as evidenced by higher oxidative rates to catabolize lipids (mitochondrial and peroxisomal) and ketogenic amino acids (leucine). ExTr had higher expression of the gluconeogenic gene, Pck1, but lower hepatic glycogen, pyruvate oxidation, incomplete fat oxidation, and total pancreas area. Interaction effects between the NPKD and ExTr were observed for intrahepatic triglycerides, as well as genes involved in gluconeogenesis, ketogenesis, mitochondrial fat oxidation, and peroxisomal markers; however, none were additive/synergistic. Rather, in each instance the interaction effects showed the NPKD and ExTr opposed each other.

Conclusions
An NPKD and an ExTr independently induce shifts in hepatic metabolic pathways, but changes do not seem to be additive/synergistic in healthy mice.
Multi-imaging study in a patient with cerebrotendinous xanthomatosis: radiology, clinic and pathology correlation of a rare condition
Authors: Dell'Aversano Orabona Giuseppina , Dato Clemente , Oliva Mariano , Ugga Lorenzo , Dotti Maria Teresa , Fratta Mario , Gisonni Pietro 
Published: August 2019

Cerebrotendinous xanthomatosis (CTX) is a rare metabolic disease with autosomal recessive inheritance. It is caused by mutations of the CYP27A1 gene, which codifies for sterol 27-hydroxylase, an enzyme that is responsible for the synthesis of cholic acids. In CTX, cholic acid synthesis is impaired, leading to accumulation of the precursor chenodessossicholic acid) in various organs and tissues. The clinical manifestations of CTX include chronic diarrhea, early-onset cataracts, tendon xanthomas and neurological disturbances. Therapy with oral chenodessossicholic acid has been shown to provide significantly better outcomes for affected individuals; therefore, recognition of this disease and awareness of its suggestive instrumental signs is extremely important. In this study, we describe the imaging findings in a 43-years-old male who was diagnosed with CTX and studied through ultrasound, CT and MRI. It is important that the neurology and radiology communities are aware of this multi-imaging findings: recognition of them is important, as due to the high variability of the manifestation of this disease; it could impact on early diagnosis of a condition rarely seen, but manageable.
Interventional radiology training: where will technology take us?
Authors: Mashar Meghavi , Nanapragasam Andrew , Haslam Philip 
Published: August 2019

Interventional radiology is a relatively young specialty, and it is undergoing a period of considerable growth. The benefits of a minimally invasive approach are clear, with smaller incisions, less pain, and faster recovery times being the principal benefits compared to surgical alternatives. Trainees need to acquire the technical skills and the clinical acumen to accurately deliver targeted treatment and safely follow up patients after the procedure. The need to maintain an efficient interventional radiology service whilst also giving sufficient time for trainee education is a challenge. In order to compensate for this, novel technologies like virtual reality (VR), augmented reality (AR), cadaveric simulation, and three-dimensional (3D) printing have been postulated as a means of supplementing training. In this article, we outline the main features of these innovative strategies and discuss the evidence base behind them. Benefits of these techniques beyond pure clinical training include the standardization of educational cases, access to training at any time, and less risk to patients. The main disadvantage is the large financial outlay required. Therefore, before widespread uptake can be recommended, further research is needed to confirm the educational benefit of these novel techniques, both in and of themselves and in comparison to existing clinical-based education.
Determining the caregivers’ burden in caregivers of patients with mental illness
Authors: Siddiqui Salma , Khalid Javeria 
Published: August 2019

Objective: To examine the factors associated with caregivers’ burden in individuals providing care to family members suffering from serious mental illness.
Methods: This Cross Sectional Study was carried out at Armed Forces Institute of Mental Health, Rawalpindi, from May 2015 to December 2015. A purposive sample of 120 family caregivers (60 males and 60 females, age range= 18-65) who were taking care of patients with serious mental illness (i.e. Major Depressive Disorder, Bipolar Disorder & Schizophrenia) for at least one year were recruited from the hospital and assessed through Zarit Burden Interview (ZBI) and Brief COPE inventory. The decline in functional status, and diminished physical capacity compromising the independent living of the care recipient was assessed through Katz Index of Independence in Activities of daily living (ADL) and Lawton Instrumental activities of daily living (IADL).
Results: The results suggest that the longer the duration of illness (F=25.71, p < 0.01), with increased impairments of care-recipients, (decline in functional status, F=21.33, p < 0.001; diminished physical capacity F =32.41, p < 0.001) the more the burden experienced by the caregivers. Moreover, caregivers who were married (t=-2.98, p < 0.01), less educated (t =5.48, p < 0.01), lived in rural area (t = -7.99, p < 0.01), had lower monthly income (t = -4.95, p < 0.01) provide longer hours of caregiving (F=19.12, p < 0.001) and used avoidant coping behavior (F= 56.37, p < 0.001) reported significantly higher caregiver burden than caregivers who were unmarried, more educated, lived in urban area and had better income.
Conclusion: The results of study demonstrate that caring for family members with serious mental illness impacts the caregivers’ wellbeing. It, therefore, highlights the need for support and counseling services for the caregivers to reduce the burden of caring.
doi: https://doi.org/10.12669/pjms.35.5.720
How to cite this:Siddiqui S, Khalid J. Determining the caregivers’ burden in caregivers of patients with mental illness. Pak J Med Sci. 2019;35(5):1329-1333. doi: https://doi.org/10.12669/pjms.35.5.720
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.
Polycystic Ovarian Syndrome: Correlation between clinical hyperandrogenism, anthropometric, metabolic and endocrine parameters
Authors: Khan Ayesha , Karim Nasim , Ainuddin Jahan Ara , Faheem Muhammad Faisal 
Published: August 2019

Objective: To evaluate the correlation between clinical hyperandrogenism-hirsutism assessed by modified Ferriman-Gallwey (F-G) score, anthropometric, metabolic and endocrine parameters among PCOS infertile women.
Methods: This observational study after approval of FRC & ERC of BUMDC was conducted from September 2018-March 2019. It included seventy women aged 20-40 years who presented in infertility clinic of a local Hospital in Karachi. After written informed consent participants were enrolled as per the inclusion criteria of the study and evaluated for cyclical pattern (oligomenorrhoea, amenorrhoea, polymenorrhea), physical (weight, height, BMI), anthropometric, (waist circumference, hip circumference, waist to hip ratio, hirsutism), metabolic (carbohydrate, lipid & protein) and endocrine parameters (serum FSH, LH, LH/FSH ratio, serum testosterone, prolactin and progesterone level). Hirsutism was assessed by visual method through modified F-G score and Pearson correlation was determined between hirsutism and other study parameters.
Results: A positive Pearson correlation is found between hirsutism and body weight, BMI, waist and hip circumference, waist to hip ratio (WHR), very low density lipoprotein, cholesterol, triglycerides and testosterone levels.
Conclusion: Hirsutism has correlation with anthropometric, metabolic and hyperandrgenic disorders in PCOS infertile women as assessed by modified F-G score.
doi: https://doi.org/10.12669/pjms.35.5.742
How to cite this:Khan A, Karim N, Ainuddin JA, Fahim MF. Polycystic Ovarian Syndrome: Correlation between clinical hyperandrogenism, anthropometric, metabolic and endocrine parameters. Pak J Med Sci. 2019;35(5):1227-1232. doi: https://doi.org/10.12669/pjms.35.5.742
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.
Gender based differences in clinical and Angiographic characteristics and outcomes of Acute Coronary Syndrome (ACS) in Asian population
Authors: Altaf Afrasyab , Shah Hammad , Salahuddin Momin 
Published: August 2019

Objective: There is very limited data about gender based differences in Acute Coronary Syndrome (ACS) in Asian population. This study was therefore aimed to ascertain gender based differences in clinical and angiographic characteristics and clinical outcomes in patient admitted with ACS.
Methods: This was a cross sectional, observational study including patients admitted with diagnosis of ACS. Patients were divided into two groups (Males and Females) and their clinical characteristics were noted. Gender based assessment was done following coronary angiography.
Results: A total of 386 patients were included, with 210 males and 176 females. Anterior wall myocardial infarction (AWMI) was present in 177(45.86%) patients. Mean age was 72.8±12.9 years in females and 66.8±11.2 years in males. Diabetes was present in 38.1% females and 31% males. Patients from rural population were 225(58.3%), while from urban 161(41.7%). Mean ejection fraction was 43.9±7.9% in women and 38.2±8.68% in males.
Conclusion: ACS was more common in males, rural population and AWMI was most common cause. Women were more elderly and had more adverse events as compared to males. Impaired renal dynamics were more commonly observed in males. Women were less aggressively treated with coronary interventions and radial approach was better tolerated regardless of gender.
doi: https://doi.org/10.12669/pjms.35.5.743
How to cite this:Altaf A, Shah H, Salahuddin M. Gender based differences in clinical and Angiographic characteristics and outcomes of Acute Coronary Syndrome (ACS) in Asian population. Pak J Med Sci. 2019;35(5):1349-1354. doi: https://doi.org/10.12669/pjms.35.5.743
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.