bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial
Authors: Eyck Ben M. , van Lanschot J. Jan B. , Hulshof Maarten C. C. M. , van der Wilk Berend J. , Shapiro Joel , van Hagen Pieter , van Berge Henegouwen Mark I. , Wijnhoven Bas P. L. , van Laarhoven Hanneke W. M. , Nieuwenhuijzen Grard A. P. , Hospers Geke A. P. , Bonenkamp Johannes J. , Cuesta Miguel A. , Blaisse Reinoud J. B. , Busch Olivier R. , Creemers Geert-Jan M. , Punt Cornelis J. A. , Plukker John Th. M. , Verheul Henk M. W. , Spillenaar Bilgen Ernst J. , van der Sangen Maurice J. C. , Rozema Tom , ten Kate Fiebo J. W. , Beukema Jannet C. , Piet Anna H. M. , van Rij Caroline M. , Reinders Janny G. , Tilanus Hugo W. , Steyerberg Ewout W. , van der Gaast Ate ,   for the CROSS Study Group
Published: April 2021

PURPOSE Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen. METHODS From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses. RESULTS The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent ( P value for interaction, P = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% v 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13). CONCLUSION The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years.
Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39)
Authors: Moore Kathleen N. , Bookman Michael , Sehouli Jalid , Miller Austin , Anderson Charles , Scambia Giovanni , Myers Tashanna , Taskiran Cagatay , Robison Katina , Mäenpää Johanna , Willmott Lyndsay , Colombo Nicoletta , Thomes-Pepin Jessica , Liontos Michalis , Gold Michael A. , Garcia Yolanda , Sharma Sudarshan K. , Darus Christopher J. , Aghajanian Carol , Okamoto Aikou , Wu Xiaohua , Safin Rustem , Wu Fan , Molinero Luciana , Maiya Vidya , Khor Victor K. , Lin Yvonne G. , Pignata Sandro 
Published: April 2021

PURPOSE To evaluate the addition of the humanized monoclonal antiprogrammed death ligand-1 (PD-L1) antibody, atezolizumab, to platinum-based chemotherapy and bevacizumab in newly diagnosed stage III or IV ovarian cancer (OC). METHODS This multicenter placebo-controlled double-blind randomized phase III trial (ClinicalTrials.gov identifier: NCT03038100 ) enrolled patients with newly diagnosed untreated International Federation of Gynecology and Obstetrics (FIGO) stage III or IV OC who either had undergone primary cytoreductive surgery with macroscopic residual disease or were planned to receive neoadjuvant chemotherapy and interval surgery. Patients were stratified by FIGO stage, Eastern Cooperative Oncology Group performance status, tumor immune cell PD-L1 staining, and treatment strategy and randomly assigned 1:1 to receive 3-weekly cycles of atezolizumab 1,200 mg or placebo (day 1, cycles 1-22), with paclitaxel plus carboplatin (day 1, cycles 1-6) plus bevacizumab 15 mg/kg (day 1, cycles 2-22), omitting perioperative bevacizumab in neoadjuvant patients. The co-primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat and PD-L1–positive populations. RESULTS Between March 8, 2017, and March 26, 2019, 1,301 patients were enrolled. The median progression-free survival was 19.5 versus 18.4 months with atezolizumab versus placebo, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.07; stratified log-rank P = .28), in the intention-to-treat population and 20.8 versus 18.5 months, respectively (hazard ratio, 0.80; 95% CI, 0.65 to 0.99; P = .038), in the PD-L1–positive population. The interim (immature) overall survival results showed no significant benefit from atezolizumab. The most common grade 3 or 4 adverse events were neutropenia (21% with atezolizumab v 21% with placebo), hypertension (18% v 20%, respectively), and anemia (12% v 12%). CONCLUSION Current evidence does not support the use of immune checkpoint inhibitors in newly diagnosed OC. Insight from this trial should inform further evaluation of immunotherapy in OC.
Impaired Function and Altered Morphology in the Skeletal Muscles of Adult Men and Women With Type 1 Diabetes
Authors: Dial Athan G , Monaco Cynthia M F , Grafham Grace K , Patel Tirth P , Tarnopolsky Mark A , Hawke Thomas J 
Published: April 2021

Abstract

Context
Previous investigations on skeletal muscle health in type 1 diabetes (T1D) have generally focused on later stages of disease progression where comorbidities are present and are posited as a primary mechanism of muscle dysfunction.

Objective
To investigate skeletal muscle function and morphology across the adult lifespan in those with and without T1D.

Design
Participants underwent maximal contraction (MVC) testing, resting muscle biopsy, and venous blood sampling.

Setting
Procedures in this study were undertaken at the McMaster University Medical Centre.

Participants
Sixty-five healthy adult (18-78 years old) men/males and women/females (T1D = 34; control = 31) matched for age/biological sex/body mass index; self-reported physical activity levels were included.

Main Outcome Measures
Our primary measure in this study was MVC, with supporting histological/immunofluorescent measures.

Results
After 35 years of age (“older adults”), MVC declined quicker in T1D subjects compared to controls. Loss of strength in T1D was accompanied by morphological changes associated with accelerated aging. Type 1 myofiber grouping was higher in T1D, and the groups were larger and more numerous than in controls. Older T1D females exhibited more myofibers expressing multiple myosin heavy chain isoforms (hybrid fibers) than controls, another feature of accelerated aging. Conversely, T1D males exhibited a shift toward type 2 fibers, with less evidence of myofiber grouping or hybrid fibers.

Conclusions
These data suggest impairments to skeletal muscle function and morphology exist in T1D. The decline in strength with T1D is accelerated after 35 years of age and may be responsible for the earlier onset of frailty, which characterizes those with diabetes.
Leptin Decreases Energy Expenditure Despite Increased Thyroid Hormone in Patients With Lipodystrophy
Authors: Grover Andrew , Quaye Emmanuel , Brychta Robert J , Christensen John , Startzell Megan S , Meehan Cristina Adelia , Valencia Areli , Marshall Brandon , Chen Kong Y , Brown Rebecca J 
Published: April 2021

Abstract

Context
Leptin is an adipokine that signals energy sufficiency. In rodents, leptin deficiency decreases energy expenditure (EE), which is corrected following leptin replacement. In humans, data are mixed regarding leptin-mediated effects on EE.

Objective
To determine the effects of metreleptin on EE in patients with lipodystrophy.

Design, setting, and patients
Nonrandomized crossover study of 25 patients with lipodystrophy (National Institutes of Health, 2013-2018).

Intervention
The initiation cohort consisted of 17 patients without prior exposure to metreleptin, studied before and after 14 days of metreleptin. The withdrawal cohort consisted of 8 previously metreleptin-treated patients, studied before and after 14 days of metreleptin withdrawal.

Main outcomes
24-h total energy expenditure (TEE), resting energy expenditure (REE), autonomic nervous system activity [heart rate variability (HrV)], plasma-free triiodothyronine (T3), free thyroxine (T4), epinephrine, norepinephrine, and dopamine.

Results
In the initiation cohort, TEE and REE decreased by 5.0% (121 ± 152 kcal/day; P = 0.006) and 5.9% (120 ± 175 kcal/day; P = 0.02). Free T3 increased by 19.4% (40 ± 49 pg/dL; P = 0.01). No changes in catecholamines or HrV were observed. In the withdrawal cohort, free T3 decreased by 8.0% (P = 0.04), free T4 decreased by 11.9% (P = 0.002), and norepinephrine decreased by 34.2% (P = 0.03), but no changes in EE, epinephrine, dopamine, or HrV were observed.

Conclusions
Metreleptin initiation decreased EE in patients with lipodystrophy, but no changes were observed after metreleptin withdrawal. Thyroid hormone was higher on metreleptin in both initiation and withdrawal cohorts. Decreased EE after metreleptin in lipodystrophy may result from reductions in energy-requiring metabolic processes that counteract increases in EE via adipose tissue-specific neuroendocrine and adrenergic signaling.
Histolysis, Histogenesis, and Differentiation during Insect Metamorphosis in Relation to Metabolic Changes
Authors: Agrell Ivar 
Published: April 2021

ABSTRACT
The most obvious change in metabolism during the more advanced type of insect metamorphosis is the change in the integral metabolic activity. After pupation there is first a marked decrease and later an increase of, for instance, the oxygen consumption. The respiratory metabolic curve is U-shaped. The cause of this change is a corresponding variation in the activity of oxidative enzyme systems. If one compares the variation of the spontaneous Mb-reduction and of the oxygen consumption in the fly Calliphora, one finds that the two curves have almost the same course (Agrell, 1947b). This shows an important co-operation of the dehydrogenase systems. The cytochrome system also shows a similar U-shaped variation during the period of metamorphosis, according to Wolsky (1938), Williams (1948) and Sacktor (1950). One limiting factor is the protein part of the enzymes, which is first broken down and later rebuilt (Agrell, 1946). Another limiting factor is the prosthetic heme group in the cytochromes (Williams, 1951). According to Sandborn & Williams (1950) there is also a change over from a cytochrome X, possibly identical with Keilin’s cytochrome E, to cytochrome C at pupation.
An RNA-binding protein fromXenopusoocytes is associated with specific message sequences
Authors: Crawford Dana R. , Richter Joel D. 
Published: April 2021

ABSTRACTMonoclonal antibodies directed against an RNA-binding protein from Xenopus oocytes were used to immunoselect messenger ribonucleoprotein (mRNP) particles. RNA was extracted from both the immunoselected and nonselected fractions and was used to direct the synthesis of oligo (dT)-primed 32P-cDNA. These two cDNA preparations were then used to probe Xenopus stage-1 oocyte cDNA libraries to identify sequences that had been specifically coimmunoselected by the antibodies. Three cDNA clones were shown to be derived specifically from the antibody-selected mRNPs. During very early oogenesis (stage 1–2), the RNA-binding protein and the three coselected mRNAs sediment in the nontranslating mRNP region of a sucrose gradient. By oocyte stage 6, the binding protein concentration decreases by as much as 22-fold relative to polyadenylated RNA. At this stage of development, the three mRNAs are found predominantly in the polysome region of a sucrose gradient. These data demonstrate that Xenopus oocytes contain an RNA-binding protein which binds specific message sequences and may regulate their expression.
Exogenous basement-membrane-like matrix stimulates adrenergic development in avian neural crest cultures
Authors: Maxwell Gerald D. , Forbes M. Elizabeth 
Published: April 2021

ABSTRACTThe development of quail trunk neural crest cultures was dramatically altered when the cultures were overlaid with a gel of reconstituted basement membrane (RBM) components derived from the Engel-breth-Holm-Swarm sarcoma. In the presence of the RBM gel overlay, the number of catecholaminepositive (CA+) cells that developed was increased 50fold, while the final number of melanocytes and total cells was only half that seen in the control cultures. The presence of the RBM gel overlay did not alter the time of onset of differentiation of the CA+ cells or melanocytes. The stimulation of CA+ cell number was not observed with type IV collagen substrates, laminin substrates or type I collagen gel overlays with or without added laminin. The stimulation of CA+ cell development was dependent on initial plating density. The number of CAT cells that developed in the presence of the RBM gel was proportional to the initial plating density at 80–320 cells mm−2, whereas no CA+ cells were observed below 20 cells mm−2 and only a few CA+ cells were detected at 40 cells mm−2. There was, however, extensive cell division and differentiation of melanocytes and unpigmented cells at the lower initial plating densities. When the RBM gel was used as a substrate, rather than as an overlay, a striking rearrangement of cells into interconnected strands was observed. After several days in culture, melanocytes, CA+ cells and unpigmented cells were present in these strands. These results indicate that molecules associated with a reconstituted basementmembrane-like matrix are a potent stimulatory influence on adrenergic development and also act to inhibit the production of other cell types in neural crest cultures.
Genetic analysis of the human Y chromosome by chromosome-mediated gene transfer
Authors: Pritchard Catrin A. , Goodfellow Peter N. 
Published: April 2021

ABSTRACT
Chromosome-mediated gene transfer (CMGT) can be used to segregate fragments of human chromosomes in human-rodent hybrid cells. As with all somatic cell genetics methods, a selection technique is needed to isolate the hybrid cell lines produced by CMGT. Expression of the MIC2 gene product on the cell surface (the 12E7 antigen) provides an endogenous selectable marker for the human Y chromosome. Using chromosome transfer followed by separation of 12E7 antigen-positive cells on the fluorescence-activated cell sorter, a series of cell lines containing segregated fragments of the Y chromosome have been derived. The possibility of using these fragments to derive fine structural mapping data for the Y chromosome is considered in this review.
Gene Activity in Early Development
Authors: Davidson Eric H. , Scott Matthew P. 
Published: April 2021

Abstract
In 1925, Edmund Wilson published the now classic third edition of his book The Cell in Development and Heredity, in which he laid out most of the important questions about developmental biology that we are still attempting to answer. In 1986, Eric Davidson published the third edition of his book Gene Activity in Early Development, in which the progress toward answering Wilson’s questions is described. Wilson (1896) is quoted: “If chromatin be the idioplasm … in which inheres the sum total of hereditary forces, and if it be equally distributed at every cell division, how can its mode of action so vary in different cells as to cause diversity of structure, i.e. differentiation?” How indeed. It would be fascinating to hear Wilson’s responses after informing him of enhancers and RNA splicing. Davidson is clearly an admirer of Wilson, and like Wilson has a broad perspective on the field which brings to the new edition the strengths of a profound knowledge of classical developmental biology together with an appreciation of the power of the new molecular methods.
Development of the two-part pattern during regeneration of the head in hydra
Authors: Bode P. M. , Awad T. A. , Koizumi O. , Nakashima Y. , Grimmelikhuijzen C. J. P. , Bode H. R. 
Published: April 2021

Abstract
The head of a hydra is composed of two parts, a domed hypostome with a mouth at the top and a ring of tentacles below. When animals are decapitated a new head regenerates. During the process of regeneration the apical tip passes through a transient stage in which it exhibits tentacle-like characteristics before becoming a hypostome. This was determined from markers which appeared before morphogenesis took place. The first was a monoclonal antibody, TS-19, that specifically binds to the ectodermal epithelial cells of the tentacles. The second was an antiserum against the peptide Arg-Phe-amide (RFamide), which in the head of hydra is specific to the sensory cells of the hypostomal apex and the ganglion cells of the lower hypostome and tentacles. The TS-19 expression and the ganglion cells with RFamide-like immunoreactivity (RLI) arose first at the apex and spread radially. Once the tentacles began evaginating in a ring, both the TS-19 antigen and RLI+ ganglion cells gradually disappeared from the presumptive hypostome area and RLI+ sensory cells appeared at the apex. By tracking tissue movements during morphogenesis it became clear that the apical cap, in which these changes took place, did not undergo tissue turnover. The implications of this tentacle-like stage for patterning the two-part head are discussed.
Head and thoracic transformations caused by ectopic expression ofAntennapediaduringDrosophiladevelopment
Authors: Gibson Greg , Gehring Walter J. 
Published: April 2021

AbstractSegmental identity in Drosophila is controlled by the activities of the homeotic genes. One such gene is Antennapedia, which is required for the proper development of the thoracic segments. Alteration of Antennapedia expression either in mutants, or artificially using an inducible promoter, can lead to alterations of segmental identity. In this report, we present the consequences of ectopic expression of the Antennapedia gene under the control of a heat-shock promoter, at distinct stages throughout Drosophila development. In young embryos, up to the stage of germband retraction, the ubiquitous expression of the Antennapedia protein causes a range of effects throughout the embryo, including failure of head involution, induction of extra denticles on the dorsal surface of the head and disruption of the prothoracic denticle belts. In older embryos, it results in larval lethality. Heat shocks during larval development can lead to defects in leg formation, but no alterations in leg identity have been observed. However, clear transformations of head towards second (meso-) thoracic segment can be induced in early third instar larvae. There is a distal-to-proximal temporal response to ectopic Antennapedia expression in the antennal disc, as evidenced by successive transformations of the arista, third antennal segment, second antennal segment and occiput towards their corresponding leg and dorsal thoracic structures. Overproduction of Antennapedia protein during the pupal stage is generally lethal. Comparison of the homeotic transformations in, and Western analysis of, different lines suggests that a relatively large amount of Antennapedia protein is required to cause antenna-to-leg transformations, and further argues that, in general, developmental programmes in the insect are well buffered against the effects of ectopic homeotic gene expression. Immunodetection of Scr and Antp protein also allows us to interpret the results in light of the hypothesis that the various selector genes compete with one another to control not only their own expression, but also that of downstream genes. The role of Antennapedia in imaginai disc determination is also discussed.
Positional signals: evidence for a possible role in muscle fibre-type patterning of the embryonic avian limb
Authors: Butler J. , Cosmos E. , Cauwenbergs P. 
Published: April 2021

Abstract
Current evidence favours the hypothesis that avian muscle fibre-type differentiation is intrinsically programmed during early embryogenesis and proceeds independent of neuronal influences (for review, Miller & Stockdale, 1987; Sanes, 1987). Previous interspecific (chick/quail) and intraspecific (chick/chick) chimaeric studies, involving the heterotopic transplantation of unsegmented somitic mesoderm, indicate that the ability of premyogenic cells to form specific limb muscles is determined by positional cues operative in the host embryo. To determine if similar influences are associated with embryonic fibre-type differentiation, the limb musculature of intraspecific (chick/chick) chimaeras was assessed using differential myosin-ATPase activity. The limb musculature analysed histochemically was derived from donor unsegmented thoracic somitic mesoderm transplanted to replace extirpated brachial somites of a host embryo at 48 –52 h in ovo. Our results demonstrated that (1) the donor tissue formed, on schedule, an appropriate brachial musculature and (2) the experimental muscles duplicated the fibre-type patterning characteristic of control muscles. Thus, our data suggest that an extramyogenic, non-neural factor(s) operative in the host limb-forming region is associated with both muscle pattern formation and muscle fibre-type pattern formation. Whether or not the same putative factor(s) influences both processes remains to be determined.
Diploid mouse embryos constructed at the late 2-cell stage from haploid parthenotes and androgenotes can develop to term
Authors: Barra J. , Renard J.-P. 
Published: April 2021

Abstract
Male and female gamete nuclei are required to ensure the full-term development of the mouse embryo. Differential expression of the two genomes has been proposed as the basis for this requirement. In order to investigate whether some interactions between the paternal and the maternal genomes are essential before or at the time of the activation of the embryonic genome, we have constructed diploid embryos from haploid parthenotes and androgenotes at the late 2-cell stage. These embryos developed to term into normal offsprings. This shows that the male and the female genomes can be activated separately and are still able to ensure complete development when put together in cytoplasm synchronized with the nuclei. These experiments also show that the egg cytoplasm does not need any male contribution before the late 2-cell stage.