bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the guided online cognitive behavioral therapy for insomnia “i-Sleep youth” improve sleep of adolescents and young adults with insomnia after childhood cancer? (MICADO-study): study protocol of a randomized controlled trial
Authors: Peersmann Shosha H. M. , van Straten Annemieke , Kaspers Gertjan J. L. , Thano Adriana , van den Bergh Esther , Grootenhuis Martha A. , van Litsenburg Raphaële R. L.
Published: April 2021

Background

Adolescents and young adults who had childhood cancer are at increased risk for insomnia, due to being critically ill during an important phase of their life for the development of good sleep habits. Insomnia is disabling and prevalent after childhood cancer (26–29%) and negatively impacts quality of life, fatigue, pain, and general functioning and is often associated with other (mental) health problems. Insomnia and a history of childhood cancer both increase the risk of adverse health outcomes, posing a double burden for adolescents who had childhood cancer. The first-line treatment for insomnia is cognitive behavioral therapy for insomnia (CBT-I). However, access to this type of care is often limited. The guided online CBT-I treatment “i-Sleep” has been developed to facilitate access via online care. i-Sleep is shown effective in adult (breast cancer) patients, but it is unknown if iCBT-I is effective in pediatric oncology.

Methods/design

We developed a youth version of i-Sleep. Our aim is to evaluate its effectiveness in a national randomized-controlled clinical trial comparing iCBT-I to a waiting-list control condition at 3 and 6 months (n = 70). The intervention group will be also assessed at 12 months to see whether the post-test effects are maintained. Adolescents and young adults aged 12–30 years with insomnia, diagnosed with (childhood) cancer, currently at least 6 months since their last cancer treatment will be eligible. Outcomes include sleep efficiency (actigraphic), insomnia severity (self-report), sleep and circadian activity rhythm parameters, fatigue, health-related quality of life, perceived cognitive functioning, chronic distress, depressive and anxiety symptoms, and intervention acceptability.

Discussion

Insomnia is prevalent in the pediatric oncology population posing a double health burden for adolescents and young adults who had childhood cancer. If guided iCBT-I is effective, guidelines for insomnia can be installed to treat insomnia and potentially improve quality of life and the health of adolescents and young adults who had childhood cancer.

Trial registration

NL7220(NTR7419; Netherlands Trial register). Registered on 2 August 2018
Whole-genome sequencing of phenotypically distinct inflammatory breast cancers reveals similar genomic alterations to non-inflammatory breast cancers
Authors: Li Xiaotong , Kumar Sushant , Harmanci Arif , Li Shantao , Kitchen Robert R. , Zhang Yan , Wali Vikram B. , Reddy Sangeetha M. , Woodward Wendy A. , Reuben James M. , Rozowsky Joel , Hatzis Christos , Ueno Naoto T. , Krishnamurthy Savitri , Pusztai Lajos , Gerstein Mark
Published: April 2021

Background

Inflammatory breast cancer (IBC) has a highly invasive and metastatic phenotype. However, little is known about its genetic drivers. To address this, we report the largest cohort of whole-genome sequencing (WGS) of IBC cases.

Methods

We performed WGS of 20 IBC samples and paired normal blood DNA to identify genomic alterations. For comparison, we used 23 matched non-IBC samples from the Cancer Genome Atlas Program (TCGA). We also validated our findings using WGS data from the International Cancer Genome Consortium (ICGC) and the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We examined a wide selection of genomic features to search for differences between IBC and conventional breast cancer. These include (i) somatic and germline single-nucleotide variants (SNVs), in both coding and non-coding regions; (ii) the mutational signature and the clonal architecture derived from these SNVs; (iii) copy number and structural variants (CNVs and SVs); and (iv) non-human sequence in the tumors (i.e., exogenous sequences of bacterial origin).

Results

Overall, IBC has similar genomic characteristics to non-IBC, including specific alterations, overall mutational load and signature, and tumor heterogeneity. In particular, we observed similar mutation frequencies between IBC and non-IBC, for each gene and most cancer-related pathways. Moreover, we found no exogenous sequences of infectious agents specific to IBC samples. Even though we could not find any strongly statistically distinguishing genomic features between the two groups, we did find some suggestive differences in IBC: (i) The MAST2 gene was more frequently mutated (20% IBC vs. 0% non-IBC). (ii) The TGF β pathway was more frequently disrupted by germline SNVs (50% vs. 13%). (iii) Different copy number profiles were observed in several genomic regions harboring cancer genes. (iv) Complex SVs were more frequent. (v) The clonal architecture was simpler, suggesting more homogenous tumor-evolutionary lineages.

Conclusions

Whole-genome sequencing of IBC manifests a similar genomic architecture to non-IBC. We found no unique genomic alterations shared in just IBCs; however, subtle genomic differences were observed including germline alterations in TGFβ pathway genes and somatic mutations in the MAST2 kinase that could represent potential therapeutic targets.
Increased collateral flow by rescue femorofemoral bypass dissolved residual thrombus in implanted iliofemoral artery stents: a case report
Authors: Haraki Tatsuo , Kondo Taichi , Kamei Izaya , Tanabe Takahiro
Published: April 2021

Background

Failed aortofemoral and femoropopliteal bypass grafts in the lower extremity artery usually result in acute limb ischemia. Endovascular treatment and surgical revascularization have been reported for limb salvage.

Case presentation

A 72-year-old Japanese man was admitted with acute limb ischemia due to failed aortofemoral and femoropopliteal bypass grafts. Endovascular treatment with balloon angioplasty, thrombectomy, and stent implantation in the long chronic total occlusion from the right common iliac artery to the superficial femoral artery did not result in efficient flow due to thrombus transfer from a failed aortofemoral bypass graft. However, a rescue femorofemoral bypass (the left femoral to the right deep femoral artery) improved his symptoms, and implanted in-stent flow was gradually recovered. Lower extremity angiography performed 5 months later confirmed the patency of the iliofemoral in-stent flow. However, the femorofemoral bypass graft was unfortunately occluded due to the progression of left external iliac artery stenosis. The patency of the iliofemoral in-stent flow was confirmed at 1 year by ultrasonography.

Conclusions

Improvement of the deep femoral artery flow plays an important role in the treatment of acute limb ischemia due to failed aortofemoral and femoropopliteal bypass grafts. Thus, increased collateral circulation to the periphery through the deep femoral artery dissolved the remaining in-stent thrombus in the iliofemoral artery.
Sustained oxygenation improvement after first prone positioning is associated with liberation from mechanical ventilation and mortality in critically ill COVID-19 patients: a cohort study
Authors:   The ICU-RER COVID-19 Collaboration, Scaramuzzo Gaetano , Gamberini Lorenzo , Tonetti Tommaso , Zani Gianluca , Ottaviani Irene , Mazzoli Carlo Alberto , Capozzi Chiara , Giampalma Emanuela , Bacchi Reggiani Maria Letizia , Bertellini Elisabetta , Castelli Andrea , Cavalli Irene , Colombo Davide , Crimaldi Federico , Damiani Federica , Fusari Maurizio , Gamberini Emiliano , Gordini Giovanni , Laici Cristiana , Lanza Maria Concetta , Leo Mirco , Marudi Andrea , Nardi Giuseppe , Papa Raffaella , Potalivo Antonella , Russo Emanuele , Taddei Stefania , Consales Guglielmo , Cappellini Iacopo , Ranieri Vito Marco , Volta Carlo Alberto , Guerin Claude , Spadaro Savino
Published: April 2021

Background

Prone positioning (PP) has been used to improve oxygenation in patients affected by the SARS-CoV-2 disease (COVID-19). Several mechanisms, including lung recruitment and better lung ventilation/perfusion matching, make a relevant rational for using PP. However, not all patients maintain the oxygenation improvement after returning to supine position. Nevertheless, no evidence exists that a sustained oxygenation response after PP is associated to outcome in mechanically ventilated COVID-19 patients. We analyzed data from 191 patients affected by COVID-19-related acute respiratory distress syndrome undergoing PP for clinical reasons. Clinical history, severity scores and respiratory mechanics were analyzed. Patients were classified as responders (≥ median PaO2/FiO2 variation) or non-responders (< median PaO2/FiO2 variation) based on the PaO2/FiO2 percentage change between pre-proning and 1 to 3 h after re-supination in the first prone positioning session. Differences among the groups in physiological variables, complication rates and outcome were evaluated. A competing risk regression analysis was conducted to evaluate if PaO2/FiO2 response after the first pronation cycle was associated to liberation from mechanical ventilation.

Results

The median PaO2/FiO2 variation after the first PP cycle was 49 [19–100%] and no differences were found in demographics, comorbidities, ventilatory treatment and PaO2/FiO2 before PP between responders (96/191) and non-responders (95/191). Despite no differences in ICU length of stay, non-responders had a higher rate of tracheostomy (70.5% vs 47.9, P = 0.008) and mortality (53.7% vs 33.3%, P = 0.006), as compared to responders. Moreover, oxygenation response after the first PP was independently associated to liberation from mechanical ventilation at 28 days and was increasingly higher being higher the oxygenation response to PP.

Conclusions

Sustained oxygenation improvement after first PP session is independently associated to improved survival and reduced duration of mechanical ventilation in critically ill COVID-19 patients.
Joint UAV channel modeling and power control for 5G IoT networks
Authors: Fu Xiuhua , Ding Tian , Peng Rongqun , Liu Cong , Cheriet Mohamed
Published: April 2021

This paper studies the communication problem between UAVs and cellular base stations in a 5G IoT scenario where multiple UAVs work together. We are dedicated to the uplink channel modeling and the performance analysis of the uplink transmission. In the channel model, we consider the impact of 3D distance and multi-UAVs reflection on wireless signal propagation. The 3D distance is used to calculate the path loss, which can better reflect the actual path loss. The power control factor is used to adjust the UAV's uplink transmit power to compensate for different propagation path losses, so as to achieve precise power control. This paper proposes a binary exponential power control algorithm suitable for 5G networked UAV transmitters and presents the entire power control process including the open-loop phase and the closed-loop phase. The effects of power control factors on coverage probability, spectrum efficiency and energy efficiency under different 3D distances are simulated and analyzed. The results show that the optimal power control factor can be found from the point of view of energy efficiency.
A new upper bound for the largest growth rate of linear Rayleigh–Taylor instability
Authors: Dou Changsheng , Wang Jialiang , Wang Weiwei
Published: April 2021

We investigate the effect of (interface) surface tensor on the linear Rayleigh–Taylor (RT) instability in stratified incompressible viscous fluids. The existence of linear RT instability solutions with largest growth rate Λ is proved under the instability condition (i.e., the surface tension coefficientϑis less than a threshold$\vartheta _{\mathrm{c}}$ϑc) by the modified variational method of PDEs. Moreover, we find a new upper bound for Λ. In particular, we directly observe from the upper bound that Λ decreasingly converges to zero asϑgoes from zero to the threshold$\vartheta _{\mathrm{c}}$ϑc.
The performance of some machine learning approaches and a rich context model in student answer prediction
Authors: Lincke Alisa , Jansen Marc , Milrad Marcelo , Berge Elias
Published: April 2021

Web-based learning systems with adaptive capabilities to personalize content are becoming nowadays a trend in order to offer interactive learning materials to cope with a wide diversity of students attending online education. Learners’ interaction and study practice (quizzing, reading, exams) can be analyzed in order to get some insights into the student’s learning style, study schedule, knowledge, and performance. Quizzing might be used to help to create individualized/personalized spaced repetition algorithm in order to improve long-term retention of knowledge and provide efficient learning in online learning platforms. Current spaced repetition algorithms have pre-defined repetition rules and parameters that might not be a good fit for students’ different learning styles in online platforms. This study uses different machine learning models and a rich context model to analyze quizzing and reading records from e-learning platform called Hypocampus in order to get some insights into the relevant features to predict learning outcome (quiz answers). By knowing the answer correctness, a learning system might be able to recommend personalized repetitive schedule for questions with maximizing long-term memory retention. Study results show that question difficulty level and incorrectly answered previous questions are useful features to predict the correctness of student’s answer. The gradient-boosted tree and XGBoost models are best in predicting the correctness of the student’s answer before answering a quiz. Additionally, some non-linear relationship was found between the reading learning material behavior in the platform and quiz performance that brings added value to the accuracy for all used models.
Maternal nutrition and its intergenerational links to non-communicable disease metabolic risk factors: a systematic review and narrative synthesis
Authors: Wilkins Elizabeth , Wickramasinghe Kremlin , Pullar Jessie , Demaio Alessandro R. , Roberts Nia , Perez-Blanco Karla-Maria , Noonan Katharine , Townsend Nick
Published: April 2021

Background

Non-communicable diseases (NCDs) are the leading cause of death and disability globally, while malnutrition presents a major global burden. An increasing body of evidence suggests that poor maternal nutrition is related to the development of NCDs and their risk factors in adult offspring. However, there has been no systematic evaluation of this evidence.

Methods

We searched eight electronic databases and reference lists for primary research published between 1 January 1996 and 31 May 2016 for studies presenting data on various dimensions of maternal nutritional status (including maternal exposure to famine, maternal gestational weight gain (GWG), maternal weight and/or body mass index (BMI), and maternal dietary intake) during pregnancy or lactation, and measures of at least one of three NCD metabolic risk factors (blood pressure, blood lipids and blood glucose) in the study population of offspring aged 18 years or over. Owing to high heterogeneity across exposures and outcomes, we employed a narrative approach for data synthesis (PROSPERO= CRD42016039244, CRD42016039247).

Results

Twenty-seven studies from 10 countries with 62,607 participants in total met our inclusion criteria. The review revealed considerable heterogeneity in findings across studies. There was evidence of a link between maternal exposure to famine during pregnancy with adverse blood pressure, blood lipid, and glucose metabolism outcomes in adult offspring in some contexts, with some tentative support for an influence of adult offspring adiposity in this relationship. However, the evidence base for maternal BMI, GWG, and dietary intake of specific nutrients during pregnancy was more limited and revealed no consistent support for a link between these exposures and adult offspring NCD metabolic risk factors.

Conclusion

The links identified between maternal exposure to famine and offspring NCD risk factors in some contexts, and the tentative support for the role of adult offspring adiposity in influencing this relationship, suggest the need for increased collaboration between maternal nutrition and NCD sectors. However, in view of the current scant evidence base for other aspects of maternal nutrition, and the overall heterogeneity of findings, ongoing monitoring and evaluation using large prospective studies and linked data sets is a major priority.
An enhanced approach to simulation-based mastery learning: optimising the educational impact of a novel, National Postgraduate Medical Boot Camp
Authors: Scahill Emma L. , Oliver Nathan G. , Tallentire Victoria R. , Edgar Simon , Tiernan James F.
Published: April 2021

Background

Simulation-based mastery learning (SBML) is an effective, evidence-based methodology for procedural skill acquisition, but its application may be limited by its resource intensive nature. To address this issue, an enhanced SBML programme has been developed by the addition of both pre-learning and peer learning components. These components allowed the enhanced programme to be scaled up and delivered to 106 postgraduate doctors participating in a national educational teaching programme.

Methods

The pre-learning component consisted of an online reading pack and videos. The peer learning component consisted of peer-assisted deliberate practice and peer observation of assessment and feedback within the SBML session. Anonymised pre- and post-course questionnaires were completed by learners who participated in the enhanced programme. A mixture of quantitative and qualitative data was obtained.

Results

Questionnaires were distributed to and completed by 50 learners. Both sections of the pre-learning component were highly rated on the basis of a seven-point Likert scale. The peer learning component was also favourably received following a Likert scale rating. Peer observation of the performance and assessment process was rated similarly by first and second learners.

The thematic analysis of the reasons for which peer-assisted deliberate practice was considered useful showed that familiarisation with equipment, the rehearsal of the procedure itself, the exchange of experiences and sharing of useful tips were important. The thematic analysis of the reasons why peer observation during ‘performance, assessment and feedback’ was useful highlighted that an ability to compare a peer’s performance to their own and learning from observing a peer’s mistakes were particularly helpful.

Conclusion

The SBML programme described has been enhanced by the addition of pre-learning and peer learning components which are educationally valued and allow its application on a national scale.
SMARCA4-deficient thoracic tumor detected by [18F]FDG PET/CT
Authors: Okazaki Tsubasa , Yokoyama Kota , Tsuchiya Jyunichi , Honda Takayuki , Ishikawa Yuya , Kirimura Susumu , Miyazaki Yasunari , Tateishi Ukihide
Published: April 2021

Background

SMARCA4-deficient thoracic tumor (SMARCA4-DTT) is a distinct entity of undifferentiated thoracic malignancies newly introduced in 2015. Due to its unique clinical characteristic with aggressive thoracic tumor mostly observed in heavy smoker man with emphysema, with poor prognosis, many physicians are becoming increasingly aware of the disease; however, reports on 2-deoxy-2-[18F] fluoroglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) have been limited; thus, this disease is not yet widely known to nuclear medicine clinicians. As a first step in discussing the usefulness of [18F]FDG PET/CT for this disease, we present a case in which [18F]FDG PET/CT played a clinically important role.

Case

A 74-year-old heavy smoker man with an anamnesis of severe emphysema characterized by pleural thickening and abnormal enhancement in CT underwent 18F-FDG PET/CT for further examination. [18F]FDG-avid pleural nodules infiltrating into the chest wall were detected and pathologically diagnosed as SMARCA4-DTT with biopsy.

Conclusion

SMARCA4-deficient thoracic tumor should be considered in a [18F]FDG-avid aggressive thoracic tumor in heavy smoker men with emphysema.
Decolorization of Malachite green dye by Stenotrophomonas maltophilia a compost bacterium
Authors: Alaya Vasudhaudupa , Kodi Rajesh Kumar , Ninganna Earanna , Gowda Balakrishna , Shivanna M. B.
Published: April 2021

Background

The release of triphenylmethane dyes, like malachite green (MG) and crystal violet (CV), into the environment is a cause of concern due to its toxicity, mutagenicity and carcinogenicity.

Result

A bacterial strain that is capable of decolorizing both dyes was isolated from the composted neem oil-seed cake. The strain was characterized asStenotrophomonas maltophiliabased on the 16S rRNA gene sequence and designated as isolate TPMD-1. The kinetic study of the dye degradation revealed the efficiency of the above isolate to degrade MG. The effect of substrate concentration, pH, temperature, and agitation on the decolorization of MG by the isolate was also studied. The MG degradation rate was slightly more in neutral pH at 28–30 °C and 150 rpm. The UV-spectroscopy, HPLC, and FTIR analyses of the dye sample before and after bacterial treatment revealed the high ability ofS. maltophiliaTPDM-1 in the removal of MG from the media. The genetic snapshot of the isolate by PCR amplification and sequencing showed the presence of genes 'lac’and ‘tmr’that codes for laccase and triphenylmethane reductase.

Conclusion

This study presented the first report ofStenotrophomonas maltophiliain the degradation and detoxification of MG dye by oxidoreduction, which could be used for the bioremediation of aquatic environments contaminated by MG.
Aversion to Off-label Prescribing in Clinical Pediatric Weight Management: The Quintessential Double Standard
Authors: San Giovanni Christine B , Sweeney Brooke , Skelton Joseph A , Kelsey Megan M , Kelly Aaron S
Published: April 2021

Context

Pediatric obesity is now recognized as a chronic disease; yet few treatment options exist besides lifestyle modification therapy and bariatric surgery. We describe the limited availability of United States Food and Drug Administration (FDA)–approved antiobesity medications for adolescents and compare this to what is available for adults. We offer a rationale for off-label prescribing to assist with lifestyle modification therapy. We also highlight the need for more pharmacotherapy options and additional research into novel treatments for pediatric obesity.

Case Description

We describe a patient who is struggling with managing her weight and starting to develop complications of obesity. We offer a framework in which off-label prescribing may be beneficial to patients who have been engaging in lifestyle modification therapy yet fail to see improvement.

Conclusion

Lifestyle modification therapy is necessary but often insufficient in stimulating clinically meaningful weight loss when used alone in children and adolescents who struggle with weight management. Until more FDA-approved antiobesity medications are available, pediatricians may be able to help more patients achieve weight reduction goals by familiarizing themselves with the responsible use of off-label medications and implementing these tools to improve clinical outcomes. There is a critical need for more pharmacotherapy options to help pediatric patients in managing their weight and preventing or improving the insidious complications resulting from untreated obesity.
Some Experiments on Sea-urchin Eggs with Desoxynucleic Acids from Sea-urchin Sperms
Authors: Hörstadius Sven
Published: April 2021

Dr. I.Joanlorch, of King’s College, London, and I have made some experiments on sea-urchin eggs with desoxynucleic acids (DNA) prepared from sperms of several sea-urchin species by Professor Erwin Chargaff, of Columbia University, New York.
Radiation Malformations Belonging to the Cyclopia–Arrhinencephalia–Otocephalia Group in the Mouse Foetus
Authors: Murakami Ujihiro , Kameyama Yoshiro , Majima Akio , Sakurai Tsuneyoshi
Published: April 2021

Mice were subjected to a single whole-body X-radiation of 200 r. on the 9th day of pregnancy and embryos and foetuses derived from them were examined from the 13th to 19th day of pregnancy. Besides some exencephalias, hydrocephaluses, harelips and cleft-palates, a spectrum of malformations grossly classified into the following three groups was observed at comparatively high frequencies (over 32 per cent.). The first group : an apparently univentricular telencephalon accompanied by a beak-like appearance of the snout and eyes approaching the median. The second group : a reduction in the size of the telencephalon associated with a tapering of the snout and a tendency to synophthalmia. The third group : the tapering snout which may be accompanied by fusing nostrils. Besides, two cases of microtia were found. Microscopic findings suggest that these three groups present a spectrum of malformations belonging to the cyclopia-arrhinencephalia-otocephalia group. However, no typical cyclopias were detected. During the most sensitive developmental stage, the 9th day of pregnancy, 3-5 brain vesicles are formed and the anterior neuropore is closed. That this phase of basic morphogenesis of the nervous system is most sensitive to teratogenic influences is in harmony with both the results of experimental embryologists employing lower vertebrates and those of human pathologists.
Teratological Changes in the Offspring of Chicken Embryos Treated with Tyrode or with Tyrode plus DNA
Authors: Martinovitch Petar N. , Kanazir Dušan T. , Kneževitch Zoran A. , Simitch Marta M.
Published: April 2021

Tyrode salt solution when injected into the blood-stream of young chicken embryos will cause the appearance of malformed embryos in the 1st and 2nd filial generation derived from the recipient birds. The frequency of malformed embryos appears to be correlated with the amount of substance injected. The rate of the appearance of malformations at least in the 1st filial generation is increased when DNA dissolved in Tyrode is injected into the recipient embryo. It also appears that the percentage of malformed embryos rises if the amount of DNA is increased by repeated intermittent injections. The recipient embryos themselves do not develop malformations unless relatively high doses are given to them by repeated injections. Tyrode solution has a definite injurious effect on the gonad of recipient female birds and on the gonads of their Fx progeny, which is expressed in a number of ways. The same effect has been observed in the recipients of both the F1 and F2 from DNA-treated birds.
Carbonic Anhydrase Activity in Early Developing Chick Embryos
Authors: Shepard Thomas H.
Published: April 2021

The wet weight of developing Heisdorf and Nelson chick embryos was found to be comparable to that of other types of chick embryos. Unexpectedly high amounts of protein were observed in homogenates of chick embryos up to the 5th day of development. The total nitrogen values of similar preparations increased steadily and were in keeping with the findings of others. The specific activity of carbonic anhydrase (units/mg. nitrogen or protein) of whole embryos increased abruptly between the 4th and 5th days. The increase occurred in both the anterior and posterior portion of the embryo and was not due solely to accumulation in the retinae. After days of development intracellular localization of carbonic anhydrase activity appeared in the soluble fraction. By the techniques used there was no change between the 1st and 5th day in the percentage distribution of protein or nitrogen in the centrifuged fractions.
The Development of an Inherited Tooth Defect in the Mouse
Authors: Grewal M. S.
Published: April 2021

Absence of third molars occurs in some inbred strains of mice (CBA and A) in which these teeth are small, and in the mutant Crooked-tail (Cd/Cd) in which all the molars and the lower incisors are reduced in size. Both in CBA and in Cd/Cd mice, the teeth which will later be absent are represented by tooth germs at first. On the 6th and 5th day after birth respectively, these tooth germs are arrested in the ‘cap’ stage or a little before. They do not invaginate to form a ‘bell’ and ultimately regress. The mechanism of this regression has not been elucidated.
The Effect of Chlorpromazine on the Embryonic Development of the Axolotl (Ambystoma mexicanum)
Authors: Eyal-Giladi Hefzibah , Eyal Zwi
Published: April 2021

Axolotl embryos at various stages of development were placed in different concentrations of chlorpromazine for varying periods of time. The embryos were then reared up to stage 46 and examined with a binocular microscope. The deleterious effect of CPZ on the embryos was found to be greater the higher the concentration and the longer the time of treatment. The following degrees in the potency of the effect were noted: (a) almost immediate stoppage of development followed by death and cytolysis; (b) development up to stage 37–38, followed by cessation of development and degeneration; (c) development to the final stage (46) accompanied by microcephaly and pronounced defects in the eyes, gills, pigmentation, and axial organs, as judged by the external appearance of the larvae; (d) development to the final stage (46) of normal larvae with a tendency to a reduced amount of melanin in the melanophores of certain parts of the body (particularly the top of the head); (e) the development of larvae which appeared to be completely normal. In the discussion an attempt was made to coordinate the arrest of development at stages 37–38 with Løvtrup and Werdinius’s respiration curve of developing axolotl embryos. It was found that these critical stages correspond to the second period of constant oxygen consumption prior to a rapid rise in respiration. The assumption was formulated that as a result of the effect of CPZ the embryos are unable to increase their respiratory rate in subsequent stages, with resultant cessation of development followed by degeneration. A comparison stressing both similarities and differences between the effects of CPZ and other teratogenic substances was made.
Increase in Cell Number as a Factor in the Growth of the Organs and Tissues of the Young Male Rat
Authors: Enesco M. , Leblond C. P.
Published: April 2021

While the organs and tissues of the young rat are known to increase in size with age (Donaldson, 1924), little is known of the role played by the component cells in this increase. There is evidence that cells enlarge (Levi, 1906; Plenk, 1911) and new cells are added (Strasburger, 1893), but we do not know to what extent the enlargement and proliferation of the cells cause the growth of organs and tissues. The present work is an attempt to clarify this problem.
Transfer of Primordial Germ-cells between Two Subspecies of Xenopus laevis
Authors: Blackler A. W.
Published: April 2021

In Anura the primordial germ-cells are discernible in the dorsal crest endoderm of tail-bud stages of development and may be traced from this position throughout their migration into the undifferentiated gonadal rudiment. These facts have been established by the descriptive studies of a number of workers (see review by Johnston, 1951), the cells being recognizable by their large size, the retention of yolk platelets long after their disappearance in neighbouring cells, the sharply defined and often kidney-shaped nuclear membrane, and the poor staining affinity of the nuclear contents.
Cell polarity during wound healing in an insect epidermis
Authors: Nubler-Jung K. , Bonitz R. , Sonnenschein M.
Published: April 2021

The insect integument displays uniform posterior orientation of cuticular denticles or bristles formed by the epidermal cells. We want to understand how cell polarities become uniformly oriented in the plane of the epidermal sheet.

Here we test whether directed cell migration disturbs the orientation of denticles. Burning a circular area of epidermal cells beneath the cuticle causes cells to migrate into the resulting wound and the cuticle pattern observed after the subsequent moult depends on the time interval between burning and ecdysis. After a short wound-healing period cuticular protrusions tend to point away from the wound. With increasing wound healing periods they tend to point more and more towards the wound centre. These results suggest that the migrating cells tend to orient cuticular protrusions in the direction of cell movement while continued cell movement will bend nascent cuticular protrusions outwards. Cell shape may also determine denticle orientation.

I propose that the asymmetric localization of cell components known to determine the . orientation of cell migration may also determine denticle orientation in insect epidermal cells.
Tissue polarity in an insect segment: denticle patterns resemble spontaneously forming fibroblast patterns
Authors: NüBler-Jung K.
Published: April 2021

The insect integument displays planar tissue polarity in the uniform posterior orientation of denticles and bristles. How do cell polarities become uniformly oriented in the plane of the epidermal sheet? We have already shown that it is possible to disturb uniform denticle orientation in abdominal segments of Dysder-cus (Nübler-Jung, 1987). Here I report that abnormally oriented denticles tend to form small arrays with uniform orientation. Adjacent arrays with divergent orientations realize a small repertory of characteristic pattern elements. We obtain these pattern elements by orthogonal transformation of pattern elements that form spontaneously in confluent fibroblast cultures, which rely on autonomous cell behaviour, and which later simplify into patterns predicted by specific boundary conditions (Elsdale & Wasoff, 1976); the only additional parameter required is planar cell polarity. The abnormal patterns in Dysdercus may thus also form spontaneously and may also rely on autonomous cell behaviour. The normal pattern is predicted by the parallel segment boundaries.

I propose that the characteristic pattern elements in the larval epidermis may arise because elongated epidermal cells tend to arrange in parallel arrays and to orient in the same direction. The normal posterior orientation of cell polarities may result from orienting cues provided by the anterior and by the posterior intersegmental regions.
The relationship between intracellular calcium levels and limb bud chondrogenesis in vitro
Authors: Bee James A. , Jeffries Ros
Published: April 2021

Under standard culture conditions, chondrogenic expression by stage-21 embryonic chick limb bud mesenchyme is dependent upon high cell plating densities. Alternatively, when cultured in suspension aggregating limb bud cells differentiate exclusively as cartilage. We have previously demonstrated that the aggregation of prechondrogenic limb bud cells is specifically mediated by a Ca2+-dependent mechanism. In the present paper, we examine the involvement of calcium cations in chondrogenic expression in vitro. During cartilage differentiation, we demonstrate that limb bud cells elevate their intracellular Ca2+ levels to achieve a conserved plateau level. This increase in intracellular Ca2+ levels does not occur in sparse cell cultures, which also fail to demonstrate cartilage differentiation. Although elevation of extracellular Ca2+ concentration effects precocious chondrogenesis, ultimately this is substantially lower than in control cultures. In contrast, elevation of intracellular Ca2+ levels by the addition of 0·1 μM-A23187 readily stimulates precocious and extensive cartilage differentiation. 0· μM-A23187 initially elevates intracellular Ca2+ levels to that required for cartilage differentiation but this then continues to increase concomitant with a reduction in cartilage nodule size. 10 μM-retinoic acid completely inhibits chondrogenesis in vitro and elevates intracellular Ca2+ to particularly high levels. Our data indicate the central role of controlled intracellular Ca2+ levels to normal chondrogenic expression. Deviation from this level by cells that either fail to achieve or that exceed it inhibits subsequent cartilage development, and can cause a loss of phenotypic expression by differentiated cartilage.
Calcium: a regulation system emerges in plant cells
Authors: Gilroy S. , Blowers D. P. , Trewavas A. J.
Published: April 2021

Calcium occupies a pre-eminent place in the cellular control systems of animals (Campbell, 1983). Because of the cytotoxic effects of calcium, cells pay very particular attention to keeping cytoplasmic calcium levels very much lower than the normal extra-cellular 10−3M level; usually it is in the range 10−8–10−6M. This is accomplished using a variety of calcium-pumping systems located both in the plasma membrane and organelles and together these operate a very efficient calcium-stat system. But, in addition, cells use the temporary elevation of cytoplasmic calcium to between 10−6 and 10−5 M that may follow plasma membrane perturbation and alteration of calcium channel activity, as signals, eliciting a variety of predetermined responses. The concentration of cytoplasmic calcium is sensed by calcium-binding proteins, most notably calmodulin, and the calcium/calmodulin complex in turn modulates the activity of numerous enzymes and proteins. Calcium is also associated with other signalling systems such as IP3 and cyclic AMP.
Segmentally repeated pattern of expression of a cell surface glycoprotein inDrosophilaembryos
Authors: Gauger Ann , Glicksman Marcie A. , Salatino Richard , Condie John M. , Schubiger Gerold , Brower Danny L.
Published: April 2021

We report here that a previously described cell surface antigen (Brower, Smith & Wilcox, 1980) is expressed in a segmentally repeating pattern of stripes in the epidermis and nervous system of segmented Drosophila embryos. We also report that the antigenic activity is found on two closely related cell surface glycoproteins. The pattern of expression of this antigen is reminiscent of the expression of some segmentation genes and is affected by mutation of at least two of these genes, fushi tarazu and paired. Thus these glycoproteins are candidates for cell surface molecules involved in carrying out the patterning processes controlled by segmentation genes.
The growth rate of sensory nerve fibres in the mammalian embryo
Authors: Davies Alun M.
Published: April 2021

I have used a novel quantitative electron microscopic method to determine the rate at which nerve fibres grow towards their targets during development. The rate of recruitment of nerve fibres to the maxillary nerve of the mouse embryo was determined by counting the number of axon profiles in the nerve sectioned close to its emergence from the trigeminal ganglion at closely staged intervals throughout its early development. The rate of change of fibre number with distance along this nerve was determined by counting the number of axon profiles at intervals along the nerve at stages during the period that fibres are growing to their targets. From these two parameters, both of which were linear functions during the mid-period of fibre recruitment to the nerve, it has been possible to calculate that embryonic sensory nerve fibres grow to their peripheral targets at the surprisingly slow rate of just over 20μmh−1.
Cytogenetic analysis of first cleavage fertilized mouse eggs following in vivo exposure to ethanol shortly before and at the time of conception
Authors: O’Neill G. T. , Kaufman M. H.
Published: April 2021

In this study, the chromosome constitution of mouse eggs exposed in vivo to a dilute solution of ethanol during specific stages of the first and second meiotic divisions was determined at the first cleavage mitosis. Exposure to ethanol prior to the completion of the second meiotic division induced an incidence (7-10 %) of aneuploidy involving only one chromosome in 98 % of malsegregation events. This investigation provides indirect evidence that ethanol may induce aneuploidy by disrupting the functioning of the meiotic spindle. Karyological analyses of chromosome spreads prepared at the first cleavage metaphase suggest that only a small proportion of the total chromosome complement may be induced to undergo malsegregation.
Monoclonal antibodies against components of the myoplasm of eggs of the ascidian Ciona intestinalis partially block the development of muscle-specific acetylcholinesterase
Authors: Nishikata Takahito , Mita-Miyazawa Izumi , Deno Takuya , Satoh Noriyuki
Published: April 2021

The myoplasm of Ciona intestinalis eggs, believed to contain cytoplasmic determinants responsible for muscle cell differentiation in ascidian embryos, emits weak pale-blue autonomous fluorescence. Utilizing this feature as a marker, the cytoplasm was isolated according to the method described by Jeffery (1985ft). Electron microscopy showed that the isolated cytoplasm contained mitochondria, pigment granules, yolk particles and fine granular materials; these are ultrastructural components of the myoplasm of the intact egg. Monoclonal antibodies were prepared against the isolated cytoplasm. Twelve monoclonal antibodies, identified by indirect immunofluorescence, stained the myoplasmic region. When unfertilized eggs were centrifuged, stratifying their mitochondria and some other cytoplasmic components, components identified by several antibodies, for example IIG6B2, remained at the peripheral cytoplasm of the egg. Other antibodies recognized components stratified as the mitochondrial layer. Four representative antibodies were microinjected into fertilized eggs in order to examine their inhibitory effects on the muscle differentiation; the IIG6B2 antibody blocked the development of muscle-specific acetylcholinesterase in more than 80 % of the embryos tested.
An analysis of proliferative activity in innervated and denervated forelimb regenerates of the newt, Notophthalmus viridescens
Authors: Goldhamer David J. , Tassava Roy A.
Published: April 2021

Pulse and continuous labelling with [3H]thymidine combined with mitotic index determinations provided data on the kinetics of cell cycling in innervated and denervated early and mid-bud forelimb blastemas of the adult newt, Notophthalmus viridescens. Most or all blastema cells cycle during regeneration and are thus part of the proliferative fraction. At any given moment, however, only 26 % of the blastema cells are actively progressing through the cell cycle, with the remainder being in a state of transient quiescence (TQ). The small size of the actively cycling (AC) population may in part explain the relatively slow rate of regeneration exhibited by the adult newt. The pulse-labelling index and mitotic index of denervated blastemas paralleled control values for 48 h following nerve withdrawal, but both parameters were significantly reduced by 72 h. By 5 days postdenervation, cell cycle activity was essentially zero. The combined pulse and continuous labelling data suggest that nerves may be primarily involved in the entry of TQ cells into the AC population, with subsequent progression through the cell cycle being less dependent on innervation. Relative to controls, no early postdenervation increases in TCA-precipitable [3H]thymidine incorporation, pulse-labelling index or mitotic index were observed.
Trophectoderm surface expression of the cell adhesion molecule cell-CAM 105 on rat blastocysts
Authors: Svalander Peter C. , Odin Per , Nilsson B. Ove , Öbrink Björn
Published: April 2021

A variety of cellular interactions is involved in the process of implantation of the mammalian embryo into the uterine tissue. Recent discoveries have demonstrated that intercellular recognition and adhesive events are governed by a class of cell surface molecules known as cell adhesion molecules (CAMs). In the present report, we have investigated the occurrence of the well-characterized cell adhesion molecule cell-CAM 105 on the surface of rat pre- and periimplantation embryos of various stages. This was carried out by indirect immunofluorescence microscopy employing affinity-purified rabbit antibodies against cell-CAM 105. The embryonal stages investigated comprised morulae, normal day-4 blastocysts, and delayed and adhesive blastocysts obtained by using the method of experimentally delayed implantation. Cell-CAM 105 was absent in the early-morula stage, but in normal day-4 blastocysts and delayed blastocysts a specific staining for cell-CAM 105 was seen on the entire surface. However, adhesive-stage blastocysts exhibited a marked polarity with staining of the polar trophoblast cells. Scanning electron microscopy of adhesive-stage blastocysts revealed that the stronger staining of the polar region was not due to a greater number of microvilli on the polar trophoblast cells. Thus, it seems as if cell-CAM 105 is lost or masked from the surface of the mural trophoblast cells of adhesive-stage rat blastocysts. Since the mural trophoblast cells are the first to adhere to the uterine luminal epithelium during the onset of implantation and subsequently invade the uterine stroma, we suggest that the apparent downregulation of cell-CAM 105 in the mural trophoblast cells might be linked to the acquisition of trophoblast invasiveness.
The effect of pancreatic mesenchyme on the differentiation of endocrine cells from gastric endoderm
Authors: Kramer Beverley , Andrew Ann , Rawdon B. B. , Becker P.
Published: April 2021

To determine whether mesenchyme plays a part in the differentiation of gut endocrine cells, proventricular endoderm from 4- to 5-day chick or quail embryos was associated with mesenchyme from the dorsal pancreatic bud of chick embryos of the same age. The combinations were grown on the chorioallantoic membranes of host chick embryos until they reached a total incubation age of 21 days. Proventricular or pancreatic endoderm of the appropriate age and species reassociated with its own mesenchyme provided the controls.

Morphogenesis in the experimental grafts corresponded closely to that in proventricular controls, i.e. the pancreatic mesenchyme supported the development of proventricular glands from proventricular endoderm. Insulin, glucagon and somatostatin cells and cells with pancreatic polypeptide-like immunoreactivity differentiated in the pancreatic controls. The latter three endocrine cell types, together with neurotensin and bombesin/gastrin-releasing polypeptide (GRP) cells, developed in proventricular controls and experimental grafts. The proportions of the major types common to proventriculus and pancreas (somatostatin and glucagon cells) were in general similar when experimental grafts were compared with proventricular controls but different when experimental and pancreatic control grafts were compared. Hence pancreatic mesenchyme did not materially affect the proportions of these three cell types in experimental grafts, induced no specific pancreatic (insulin) cell type and allowed the differentiation of the characteristic proventricular endocrine cell types, neurotensin and bombesin/GRP cells. However, an important finding was a significant reduction in the proportion of bombesin/GRP cells, attributable in part to a decrease in their number and in part to an increase in the numbers of endocrine cells of the other types. This indicates that mesenchyme may well play a part in determining the regional specificity of populations of gut endocrine cells.