bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotherapy for Muscle-Invasive Bladder Cancer: Better Late Than Never?
Authors: Sonpavde Guru , Gordetsky Jennifer B. , Lockhart Mark E. , Nix Jeffrey W. 
Published: January 2016

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 64-year-old man with a history of cigarette smoking but no significant comorbidities presented with hematuria and dysuria. Computed tomography scans demonstrated a mass and thickening of the bladder wall and no evidence of metastasis. His laboratory evaluation showed normal blood cell counts and comprehensive metabolic panel with a calculated creatinine clearance of more than 60 mL per minute. A transurethral resection of the bladder tumor and biopsy identified transitional cell carcinoma or urothelial carcinoma invading the muscularis propria of the bladder. On the basis of the bladder-confined mass on computed tomography scan, the tumor was assigned a clinical stage of cT2N0. The patient was advised to undergo neoadjuvant chemotherapy followed by radical cystectomy (RC). The patient had multiple concerns regarding neoadjuvant chemotherapy, particularly toxicities, especially the possibility of chronic neurologic and renal toxicities, and the potential harm from delay of RC, especially if the bladder cancer was resistant to chemotherapy. After a discussion of approximately 1 hour, he elected to proceed with upfront RC and extended lymph node dissection in conjunction with construction of a neobladder. Pathology revealed pathologic extravesical urothelial carcinoma, with disease in one of 25 lymph nodes removed (ypT3N1). Four weeks after RC, he returned to discuss further management with the medical oncologist. He exhibited an Eastern Cooperative Oncology Group performance status of 0, normal blood cell counts, and a calculated creatinine clearance of more than 60 mL per minute.
Trends in the Aggressiveness of End-of-Life Cancer Care in the State of Qatar
Authors: Hassan Azza A. , Mohsen Hassan , Allam Ayman A. , Haddad Pascale 
Published: January 2016

Purpose Quality of end-of-life (EOL) care is a key component of excellence in cancer care, and monitoring indicators for quality of EOL cancer care is crucial to providing excellent care. The aim of the current study is to describe the relative aggressiveness of EOL cancer care in the state of Qatar and to compare it with international figures. Methods We analyzed all deaths from cancer in Qatar between January 1, 2009 and December 31, 2013. A total of 784 eligible patients were studied to assess aggressiveness of cancer care at EOL. Results The average number of intensive care unit admissions per person decreased from 0.44 to 0.22 (P < .001) over the period of study. In addition, patients spent fewer days in the intensive care unit (2.79 to 1.82 days; P = .006) and made fewer visits to the emergency department (1.00 to 0.52 visits; P < .001) in the last 30 days of life. Fewer patients had at least one aggressive treatment measure at EOL during the 5-year period (82.3% to 71.0%; P = .038). The mean composite score for aggressiveness of EOL care decreased from 2.24 to 1.92 (P < .01). Conclusion The aggressiveness of EOL cancer care has significantly decreased over time in Qatar; however, despite this decrease, the rate is still higher than that reported internationally. The integration of community palliative care services in Qatar may further decrease the aggressiveness of cancer care at EOL.
Icam5 Expression Exhibits Sex Differences in the Neonatal Pituitary and Is Regulated by Estradiol and Bisphenol A
Authors: Eckstrum Kirsten S. , Weis Karen E. , Baur Nicholas G. , Yoshihara Yoshihiro , Raetzman Lori T. 
Published: January 2016

Abstract
Endocrine-disrupting chemicals are prevalent in the environment and can impair reproductive success by affecting the hypothalamic-pituitary-gonadal axis. The developing pituitary gland is sensitive to exposure to endocrine-disrupting chemicals, such as bisphenol A (BPA), and sex-specific effects can occur. However, effects on the critical window of neonatal pituitary gland development in mice have not been explored. Therefore, this study determined baseline gene expression in male and female pituitaries and consequences of environmental exposure to 17β-estradiol (E2) and BPA on transcription of genes exhibiting sex differences during the neonatal period. Through microarray and quantitative RT-PCR analysis of pituitaries at postnatal day (PND)1, 3 genes were differentially expressed between males and females: Lhb, Fshb, and intracellular adhesion molecule-5 (Icam5). To see whether E2 and BPA exposure regulates these genes, pituitaries were cultured at PND1 with 10−8M E2 or 4.4 × 10−6M BPA. E2 decreased expression of Lhb, Fshb, and Icam5 mRNA in females but only significantly decreased expression of Icam5 in males. BPA decreased expression of Icam5 similarly to E2, but it did not affect Lhb or Fshb. Importantly, in vivo exposure to 50-μg/kg · d E2 from PND0 to PND7 decreased expression of Lhb, Fshb, and Icam5 mRNA in both males and females, whereas 50-mg/kg · d BPA exposure during the same time frame decreased expression of Icam5 in females only. Overall, we have uncovered that genes differentially expressed between the sexes can be regulated in part by hormonal and chemical signals in vivo and directly at the pituitary and can be regulated in a sex-specific manner.
The Urine Iodine to Creatinine as an Optimal Index of Iodine During Pregnancy in an Iodine Adequate Area in China
Authors: Li Chenyan , Peng Shiqiao , Zhang Xiaomei , Xie Xiaochen , Wang Danyang , Mao Jinyuan , Teng Xiaochun , Shan Zhongyan , Teng Weiping 
Published: January 2016

AbstractContext:Iodine nutrition is a global event, especially for pregnant women.Objective:To develop applicable index of iodine intake for population during pregnancy.Design, Setting, and Participants:From 2012 to 2014, pregnant women at less than 8 weeks of gestation (n = 222) and reproductive-age women (n = 827) participated in this study. The pregnant women were evaluated at follow-up visits at 8, 12, 16, 20, 28, and 36 weeks of gestation and 3 and 6 months postpartum.Main Outcome Measures:Twenty-four-hour urine samples were collected at weeks 8 of gestation. Urine iodine (UI) and creatinine (Cr) and serum thyroglobulin were measured in all of the subjects. Circulatory iodine was measured using inductively coupled plasma-mass spectrometry at 8, 20, and 36 weeks of gestation and 6 months postpartum.Results:The median UI concentration decreased from 183.6 to 104.2 μg/L during pregnancy. The serum iodine (SI) changes were similar to the UI to creatinine ratio (UI/Cr). The SI level was lowest at the eighth week of gestation (60.5 μg/L), which rose significantly until 20 weeks (106.5 μg/L) and then began to decline (36 wk, 84.7 μg/L). The 24-hour UI excretion measurement was regarded as the gold standard. The area under the receiver-operating characteristic curve for UI/Cr was 0.92 for iodine deficiency diagnoses and 0.78 for SI. The area for SI was 0.82 for excessive iodine diagnoses and 0.75 for UI/Cr. The areas under these curves were significantly different (P &lt; .001). The areas under the receiver-operating characteristic curve for UI were 0.61 (P = .11) and 0.65 (P = .08) for iodine deficiency and excessive iodine diagnoses, respectively. Additionally, for thyroglobulin, these values were 0.54 (P = .53) and 0.53 (P = .74), respectively.Conclusions:Iodine intake, as assessed by spot UI concentration in pregnant women, is inaccurate and increases the prevalence of iodine deficiency. The UI/Cr better reflects the 24-hour iodine excretion and circulating iodine levels during pregnancy and the postpartum period.
Early and Sustained Changes in Bone Metabolism After Severe Burn Injury
Authors: Muschitz Gabriela Katharina , Schwabegger Elisabeth , Kocijan Roland , Baierl Andreas , Moussalli Hervé , Fochtmann Alexandra , Nickl Stefanie , Tinhofer Ines , Haschka Judith , Resch Heinrich , Rath Thomas , Pietschmann Peter , Muschitz Christian 
Published: January 2016

Abstract

Context:
Severe burn injury causes a massive stress response, consecutively heightened serum levels of acute phase proteins, cortisol, and catecholamines with accompanying disturbance in calcium metabolism.

Objective:
Evaluation of early and prolonged changes of serum bone turnover markers (BTMs) and regulators of bone metabolism.

Design:
Longitudinal observational design.

Setting:
University clinic.

Patients:
A total of 32 male patients with a median age of 40.5 years and a median burned total body surface area of 40% (83% patients with full thickness burn injury).

Interventions:
None.

Main Outcome Measures:
Comparison of changes of BTM/regulators of bone metabolism in the early (d 2–7) and prolonged (d 7–56) phases after trauma.

Results:
All investigated BTM/regulators significantly changed. During the early phase, pronounced increases were observed for serum type 1 collagen cross-linked C-telopeptide, intact N-terminal propeptide of type I procollagen, sclerostin, Dickkopf-1, bone-specific alkaline phosphatase, fibroblast growth factor 23, and intact parathyroid hormone levels, whereas 25-hydroxyvitamin D, albumin, serum, and ionized calcium levels decreased. Changes of osteoprotegerin, osteocalcin, and phosphate were less pronounced but remained significant. In the prolonged phase, changes of intact N-terminal propeptide of type I procollagen were most pronounced, followed by elevated sclerostin, osteocalcin, bone-specific alkaline phosphatase, and lesser changes for albumin levels. Calcium and ionized calcium levels tardily increased and remained within the limit of normal. In contrast, levels of intact parathyroid hormone, fibroblast growth factor 23, C-reactive protein, and to a lesser extent serum type 1 collagen cross-linked C-telopeptide and phosphate levels declined significantly during this phase of investigation.

Conclusions:
Ongoing changes of BTM and regulators of bone metabolism suggest alterations in bone metabolism with a likely adverse influence on bone quality and structure in male patients with severe burn injuries.
Cellular structural biology as revealed by cryo-electron tomography
Authors: Irobalieva Rossitza N. , Martins Bruno , Medalia Ohad 
Published: January 2016

ABSTRACT
Understanding the function of cellular machines requires a thorough analysis of the structural elements that underline their function. Electron microscopy (EM) has been pivotal in providing information about cellular ultrastructure, as well as macromolecular organization. Biological materials can be physically fixed by vitrification and imaged with cryo-electron tomography (cryo-ET) in a close-to-native condition. Using this technique, one can acquire three-dimensional (3D) information about the macromolecular architecture of cells, depict unique cellular states and reconstruct molecular networks. Technical advances over the last few years, such as improved sample preparation and electron detection methods, have been instrumental in obtaining data with unprecedented structural details. This presents an exciting opportunity to explore the molecular architecture of both individual cells and multicellular organisms at nanometer to subnanometer resolution. In this Commentary, we focus on the recent developments and in situ applications of cryo-ET to cell and structural biology.
Nonsense-mediated mRNA decay in humans at a glance
Authors: Kurosaki Tatsuaki , Maquat Lynne E. 
Published: January 2016

ABSTRACT
Nonsense-mediated mRNA decay (NMD) is an mRNA quality-control mechanism that typifies all eukaryotes examined to date. NMD surveys newly synthesized mRNAs and degrades those that harbor a premature termination codon (PTC), thereby preventing the production of truncated proteins that could result in disease in humans. This is evident from dominantly inherited diseases that are due to PTC-containing mRNAs that escape NMD. Although many cellular NMD targets derive from mistakes made during, for example, pre-mRNA splicing and, possibly, transcription initiation, NMD also targets ∼10% of normal physiological mRNAs so as to promote an appropriate cellular response to changing environmental milieus, including those that induce apoptosis, maturation or differentiation. Over the past ∼35 years, a central goal in the NMD field has been to understand how cells discriminate mRNAs that are targeted by NMD from those that are not. In this Cell Science at a Glance and the accompanying poster, we review progress made towards this goal, focusing on human studies and the role of the key NMD factor up-frameshift protein 1 (UPF1).
Neural control of lengthening contractions
Authors: Duchateau Jacques , Enoka Roger M. 
Published: January 2016

ABSTRACTA number of studies over the last few decades have established that the control strategy employed by the nervous system during lengthening (eccentric) differs from those used during shortening (concentric) and isometric contractions. The purpose of this review is to summarize current knowledge on the neural control of lengthening contractions. After a brief discussion of methodological issues that can confound the comparison between lengthening and shortening actions, the review provides evidence that untrained individuals are usually unable to fully activate their muscles during a maximal lengthening contraction and that motor unit activity during submaximal lengthening actions differs from that during shortening actions. Contrary to common knowledge, however, more recent studies have found that the recruitment order of motor units is similar during submaximal shortening and lengthening contractions, but that discharge rate is systematically lower during lengthening actions. Subsequently, the review examines the mechanisms responsible for the specific control of maximal and submaximal lengthening contractions as reported by recent studies on the modulation of cortical and spinal excitability. As similar modulation has been observed regardless of contraction intensity, it appears that spinal and corticospinal excitability are reduced during lengthening compared with shortening and isometric contractions. Nonetheless, the modulation observed during lengthening contractions is mainly attributable to inhibition at the spinal level.
Contribution of elastic tissues to the mechanics and energetics of muscle function during movement
Authors: Roberts Thomas J. 
Published: January 2016

ABSTRACTMuscle force production occurs within an environment of tissues that exhibit spring-like behavior, and this elasticity is a critical determinant of muscle performance during locomotion. Muscle force and power output both depend on the speed of contraction, as described by the isotonic force-velocity curve. By influencing the speed of contractile elements, elastic structures can have a profound effect on muscle force, power and work. In very rapid movements, elastic mechanisms can amplify muscle power by storing the work of muscle contraction slowly and releasing it rapidly. When energy must be dissipated rapidly, such as in landing from a jump, energy stored rapidly in elastic elements can be released more slowly to stretch muscle contractile elements, reducing the power input to muscle and possibly protecting it from damage. Elastic mechanisms identified so far rely primarily on in-series tendons, but many structures within muscles exhibit spring-like properties. Actomyosin cross-bridges, actin and myosin filaments, titin, and the connective tissue scaffolding of the extracellular matrix all have the potential to store and recover elastic energy during muscle contraction. The potential contribution of these elements can be assessed from their stiffness and estimates of the strain they undergo during muscle function. Such calculations provide boundaries for the possible roles these springs might play in locomotion, and may help to direct future studies of the uses of elastic elements in muscle.
Muscle memory and a new cellular model for muscle atrophy and hypertrophy
Authors: Gundersen Kristian 
Published: January 2016

ABSTRACTMemory is a process in which information is encoded, stored, and retrieved. For vertebrates, the modern view has been that it occurs only in the brain. This review describes a cellular memory in skeletal muscle in which hypertrophy is ‘remembered’ such that a fibre that has previously been large, but subsequently lost its mass, can regain mass faster than naive fibres. A new cell biological model based on the literature, with the most reliable methods for identifying myonuclei, can explain this phenomenon. According to this model, previously untrained fibres recruit myonuclei from activated satellite cells before hypertrophic growth. Even if subsequently subjected to grave atrophy, the higher number of myonuclei is retained, and the myonuclei seem to be protected against the elevated apoptotic activity observed in atrophying muscle tissue. Fibres that have acquired a higher number of myonuclei grow faster when subjected to overload exercise, thus the nuclei represent a functionally important ‘memory’ of previous strength. This memory might be very long lasting in humans, as myonuclei are stable for at least 15 years and might even be permanent. However, myonuclei are harder to recruit in the elderly, and if the long-lasting muscle memory also exists in humans, one should consider early strength training as a public health advice. In addition, myonuclei are recruited during steroid use and encode a muscle memory, at least in rodents. Thus, extending the exclusion time for doping offenders should be considered.
The sarcomeric cytoskeleton: from molecules to motion
Authors: Gautel Mathias , Djinović-Carugo Kristina 
Published: January 2016

ABSTRACT
Highly ordered organisation of striated muscle is the prerequisite for the fast and unidirectional development of force and motion during heart and skeletal muscle contraction. A group of proteins, summarised as the sarcomeric cytoskeleton, is essential for the ordered assembly of actin and myosin filaments into sarcomeres, by combining architectural, mechanical and signalling functions. This review discusses recent cell biological, biophysical and structural insight into the regulated assembly of sarcomeric cytoskeleton proteins and their roles in dissipating mechanical forces in order to maintain sarcomere integrity during passive extension and active contraction. α-Actinin crosslinks in the Z-disk show a pivot-and-rod structure that anchors both titin and actin filaments. In contrast, the myosin crosslinks formed by myomesin in the M-band are of a ball-and-spring type and may be crucial in providing stable yet elastic connections during active contractions, especially eccentric exercise.
Metabolic fuel kinetics in fish: swimming, hypoxia and muscle membranes
Authors: Weber Jean-Michel , Choi Kevin , Gonzalez Alex , Omlin Teye 
Published: January 2016

ABSTRACT
Muscle performance depends on the supply of metabolic fuels and disposal of end-products. Using circulating metabolite concentrations to infer changes in fluxes is highly unreliable because the relationship between these parameters varies greatly with physiological state. Quantifying fuel kinetics directly is therefore crucial to the understanding of muscle metabolism. This review focuses on how carbohydrates, lipids and amino acids are provided to fish muscles during hypoxia and swimming. Both stresses force white muscle to produce lactate at higher rates than it can be processed by aerobic tissues. However, lactate accumulation is minimized because disposal is also strongly stimulated. Exogenous supply shows that trout have a much higher capacity to metabolize lactate than observed during hypoxia or intense swimming. The low density of monocarboxylate transporters and their lack of upregulation with exercise explain the phenomenon of white muscle lactate retention. This tissue operates as a quasi-closed system, where glycogen stores act as an ‘energy spring’ that alternates between explosive power release during swimming and slow recoil from lactate in situ during recovery. To cope with exogenous glucose, trout can completely suppress hepatic production and boost glucose disposal. Without these responses, glycemia would increase four times faster and reach dangerous levels. The capacity of salmonids for glucoregulation is therefore much better than presently described in the literature. Instead of albumin-bound fatty acids, fish use lipoproteins to shuttle energy from adipose tissue to working muscles during prolonged exercise. Proteins may play an important role in fueling muscle work in fish, but their exact contribution is yet to be established. The membrane pacemaker theory of metabolism accurately predicts general properties of muscle membranes such as unsaturation, but it does not explain allometric patterns of specific fatty acids. Investigations of metabolic fuel kinetics carried out in fish to date have demonstrated that these ectotherms use several unique strategies to orchestrate energy supply to working muscles and to survive hypoxia.
Skeletal muscle mass and composition during mammalian hibernation
Authors: Cotton Clark J. 
Published: January 2016

ABSTRACTHibernation is characterized by prolonged periods of inactivity with concomitantly low nutrient intake, conditions that would typically result in muscle atrophy combined with a loss of oxidative fibers. Yet, hibernators consistently emerge from winter with very little atrophy, frequently accompanied by a slight shift in fiber ratios to more oxidative fiber types. Preservation of muscle morphology is combined with down-regulation of glycolytic pathways and increased reliance on lipid metabolism instead. Furthermore, while rates of protein synthesis are reduced during hibernation, balance is maintained by correspondingly low rates of protein degradation. Proposed mechanisms include a number of signaling pathways and transcription factors that lead to increased oxidative fiber expression, enhanced protein synthesis and reduced protein degradation, ultimately resulting in minimal loss of skeletal muscle protein and oxidative capacity. The functional significance of these outcomes is maintenance of skeletal muscle strength and fatigue resistance, which enables hibernating animals to resume active behaviors such as predator avoidance, foraging and mating immediately following terminal arousal in the spring.