bluuebunny/crossref_metadata_2025_split huggingface dataset:
Change of cortical foot activation following 70 days of head-down bed rest
Authors: Yuan Peng , Koppelmans Vincent , Reuter-Lorenz Patricia , De Dios Yiri , Gadd Nichole , Riascos Roy , Kofman Igor , Bloomberg Jacob , Mulavara Ajitkumar , Seidler Rachael D. 
Published: February 2018

Head-down tilt bed rest (HDBR) has been used as a spaceflight analog to study some of the effects of microgravity on human physiology, cognition, and sensorimotor functions. Previous studies have reported declines in balance control and functional mobility after spaceflight and HDBR. In this study we investigated how the brain activation for foot movement changed with HDBR. Eighteen healthy men participated in the current HDBR study. They were in a 6° head-down tilt position continuously for 70 days. Functional MRI scans were acquired to estimate brain activation for foot movement before, during, and after HDBR. Another 11 healthy men who did not undergo HDBR participated as control subjects and were scanned at four time points. In the HDBR subjects, the cerebellum, fusiform gyrus, hippocampus, and middle occipital gyrus exhibited HDBR-related increases in activation for foot tapping, whereas no HDBR-associated activation decreases were found. For the control subjects, activation for foot tapping decreased across sessions in a couple of cerebellar regions, whereas no activation increase with session was found. Furthermore, we observed that less HDBR-related decline in functional mobility and balance control was associated with greater pre-to-post HDBR increases in brain activation for foot movement in several cerebral and cerebellar regions. Our results suggest that more neural control is needed for foot movement as a result of HDBR. NEW & NOTEWORTHY Long-duration head-down bed rest serves as a spaceflight analog research environment. We show that brain activity in the cerebellum and visual areas during foot movement increases from pre- to post-bed rest and then shows subsequent recovery. Greater increases were seen for individuals who exhibited less decline in functional mobility and balance control, suggestive of adaptive changes in neural control with long-duration bed rest.
Selective modulation of visual sensitivity during fixation
Authors: Scholes Chris , McGraw Paul V. , Roach Neil W. 
Published: February 2018

During periods of steady fixation, we make small-amplitude ocular movements, termed microsaccades, at a rate of 1–2 every second. Early studies provided evidence that visual sensitivity is reduced during microsaccades—akin to the well-established suppression associated with larger saccades. However, the results of more recent work suggest that microsaccades may alter retinal input in a manner that enhances visual sensitivity to some stimuli. Here we parametrically varied the spatial frequency of a stimulus during a detection task and tracked contrast sensitivity as a function of time relative to microsaccades. Our data reveal two distinct modulations of sensitivity: suppression during the eye movement itself and facilitation after the eye has stopped moving. The magnitude of suppression and facilitation of visual sensitivity is related to the spatial content of the stimulus: suppression is greatest for low spatial frequencies, while sensitivity is enhanced most for stimuli of 1–2 cycles/°, spatial frequencies at which we are already most sensitive in the absence of eye movements. We present a model in which the tuning of suppression and facilitation is explained by delayed lateral inhibition between spatial frequency channels. Our data show that eye movements actively modulate visual sensitivity even during fixation: the detectability of images at different spatial scales can be increased or decreased depending on when the image occurs relative to a microsaccade. NEW & NOTEWORTHY Given the frequency with which we make microsaccades during periods of fixation, it is vital that we understand how they affect visual processing. We demonstrate two selective modulations of contrast sensitivity that are time-locked to the occurrence of a microsaccade: suppression of low spatial frequencies during each eye movement and enhancement of higher spatial frequencies after the eye has stopped moving. These complementary changes may arise naturally because of sluggish gain control between spatial channels.
White Matter Damage in 4,725 Term-Born Infants Is Determined by Head Circumference at Birth: The Missing Link
Authors: Jensen Arne , Holmer Bert 
Published: February 2018

Background. White matter damage (WMD) is a prime risk factor for cerebral palsy, in part occurring unexplained. Though primarily a problem of preterm infants, there is growing evidence that in large newborns cephalopelvic disproportion and prolonged labor are involved. Objective. To explore both incidence of and morphometric risk factors for WMD in term-born infants. Study Design. We related growth variables and risk factors of term-born infants to WMD (61/4,725) using odds ratios of z-score bands. Results. The key result is the novel observation that head circumference is a prime and unique index for WMD in term-born neonates over the whole range of centiles (U-shaped; WMD (%) = 3.1168–0.12797∗HC (centile) + 0.0014741∗HC2; p<0.0001). This suggests different mechanisms for WMD in the lowest and highest z-score band. In the latter, cephalic pressure gradients and prolonged labor with preserved neonatal vitality prevail, whereas in the previous one, acute and chronic oxygen deprivation with reduced vitality predominate. Conclusions. The fact that seemingly healthy term-born neonates are not screened by head imaging, in spite of both large head circumference and prolonged labor, is considered to be the missing link between the insult that escapes diagnosis and the development of unexplained developmental delay and cerebral palsy in childhood.Dedicated to Lawrence D. Longo (1926–2016)
Predictive Gene Signatures Determine Tumor Sensitivity to MDM2 Inhibition
Authors: Ishizawa Jo , Nakamaru Kenji , Seki Takahiko , Tazaki Koichi , Kojima Kensuke , Chachad Dhruv , Zhao Ran , Heese Lauren , Ma Wencai , Ma Man Chun John , DiNardo Courtney , Pierce Sherry , Patel Keyur P. , Tse Archie , Davis R. Eric , Rao Arvind , Andreeff Michael 
Published: February 2018

Abstract
Early clinical trials using murine double minute 2 (MDM2) inhibitors demonstrated proof-of-concept of p53-induced apoptosis by MDM2 inhibition in cancer cells; however, not all wild-type TP53 tumors are sensitive to MDM2 inhibition. Therefore, more potent inhibitors and biomarkers predictive of tumor sensitivity are needed. The novel MDM2 inhibitor DS-3032b is 10-fold more potent than the first-generation inhibitor nutlin-3a. TP53 mutations were predictive of resistance to DS-3032b, and allele frequencies of TP53 mutations were negatively correlated with sensitivity to DS-3032b. However, sensitivity to DS-3032b of TP53 wild-type tumors varied greatly. We thus used two methods to create predictive gene signatures. First, by comparing sensitivity to MDM2 inhibition with basal mRNA expression profiles in 240 cancer cell lines, a 175-gene signature was defined and validated in patient-derived tumor xenograft models and ex vivo human acute myeloid leukemia (AML) cells. Second, an AML-specific 1,532-gene signature was defined by performing random forest analysis with cross-validation using gene expression profiles of 41 primary AML samples. The combination of TP53 mutation status with the two gene signatures provided the best positive predictive values (81% and 82%, compared with 62% for TP53 mutation status alone). In addition, the top-ranked 50 genes selected from the AML-specific 1,532-gene signature conserved high predictive performance, suggesting that a more feasible size of gene signature can be generated through this method for clinical implementation. Our model is being tested in ongoing clinical trials of MDM2 inhibitors.
Significance: This study demonstrates that gene expression profiling combined with TP53 mutational status predicts antitumor effects of MDM2 inhibitors in vitro and in vivo. Cancer Res; 78(10); 2721–31. ©2018 AACR.
Loss of Pax5 Exploits Sca1-BCR-ABLp190 Susceptibility to Confer the Metabolic Shift Essential for pB-ALL
Authors: Martín-Lorenzo Alberto , Auer Franziska , Chan Lai N. , García-Ramírez Idoia , González-Herrero Inés , Rodríguez-Hernández Guillermo , Bartenhagen Christoph , Dugas Martin , Gombert Michael , Ginzel Sebastian , Blanco Oscar , Orfao Alberto , Alonso-López Diego , Rivas Javier De Las , García-Cenador Maria B. , García-Criado Francisco J. , Müschen Markus , Sánchez-García Isidro , Borkhardt Arndt , Vicente-Dueñas Carolina , Hauer Julia 
Published: February 2018

Abstract
Preleukemic clones carrying BCR-ABLp190 oncogenic lesions are found in neonatal cord blood, where the majority of preleukemic carriers do not convert into precursor B-cell acute lymphoblastic leukemia (pB-ALL). However, the critical question of how these preleukemic cells transform into pB-ALL remains undefined. Here, we model a BCR-ABLp190 preleukemic state and show that limiting BCR-ABLp190 expression to hematopoietic stem/progenitor cells (HS/PC) in mice (Sca1-BCR-ABLp190) causes pB-ALL at low penetrance, which resembles the human disease. pB-ALL blast cells were BCR-ABL–negative and transcriptionally similar to pro-B/pre-B cells, suggesting disease onset upon reduced Pax5 functionality. Consistent with this, double Sca1-BCR-ABLp190+Pax5+/− mice developed pB-ALL with shorter latencies, 90% incidence, and accumulation of genomic alterations in the remaining wild-type Pax5 allele. Mechanistically, the Pax5-deficient leukemic pro-B cells exhibited a metabolic switch toward increased glucose utilization and energy metabolism. Transcriptome analysis revealed that metabolic genes (IDH1, G6PC3, GAPDH, PGK1, MYC, ENO1, ACO1) were upregulated in Pax5-deficient leukemic cells, and a similar metabolic signature could be observed in human leukemia. Our studies unveil the first in vivo evidence that the combination between Sca1-BCR-ABLp190 and metabolic reprogramming imposed by reduced Pax5 expression is sufficient for pB-ALL development. These findings might help to prevent conversion of BCR-ABLp190 preleukemic cells.
Significance: Loss of Pax5 drives metabolic reprogramming, which together with Sca1-restricted BCR-ABL expression enables leukemic transformation. Cancer Res; 78(10); 2669–79. ©2018 AACR.
Divine Embodiment in Philo of Alexandria
Authors: Forger Deborah 
Published: February 2018

AbstractBecause later polemics established Jews and Christians as binary opposites, distinguished largely by their views on God’s body, scholars have not sufficiently explored how other Jews in the early Roman period, who stood outside the Jesus movement, conceived of how the divine could become embodied on earth. The first-century Jewish philosopher Philo of Alexandria often operates as the quintessential representative of a Jew who stressed God’s absolute incorporeality. Here I demonstrate how Philo also presents a means by which a part of Israel’s God could become united with human materiality, showing how the patriarchs and Moses function as his paradigms. This evidence suggests that scholarship on divine embodiment has been limited by knowledge of later developments in Christian theology. Incarnational formulas, like that found in John 1:14 were not the only way that Jews in the first and second centuryCEunderstood that God could become united with human form.
SEIMC's and the Teacher of Children with Learning Disabilities: A Useful Partnership
Authors: McCarthy James J. 
Published: February 2018

1. The present state of affairs in the field of learning disabilities suggests that a practitioner in this area be eclectic. 2. Being eclectic requires an intimate knowledge of what is currently available for use with children having learning disabilities, along with a skill in experimenting with various approaches in the classroom. Moreover, eclecticism is not in accord with the unitheoretical preservice work that many of today's practitioners have received. Accordingly, it is not without some effort that one accepts this view, for eclecticism requires a change in the manner of doing business. 3. SEIMC's and their local branches are in a position to assist in (a) making a wide variety of materials available, and (b) advising the practitioner on directions for use, applicability, and effectiveness. In-service training sessions are, or will be, available to the practitioner; hopefully the substance of these sessions will feed back into preservice training. The inextricable bond between materials and methods suggests that both be carefully considered in the educational act. The birth and development of SEIMC's have given new impetus to exploring the contributions of materials to this act, and have thereby opened up many questions about research and professional training in special education. SEIMC's in time may have a profound influence on the fiber of special education. The newest and most ambiguous categorical area of special education is learning disabilities. Its practitioners can probably profit more than most special educators from a close and continuous contact with the SEIMC's because of (a) the present ambiguity of their field, and (b) the rather intimate way that materials relate to their teaching act. In terms of long range goals, the field of learning disabilities and the SEIMC's overlap and appear to be mutually enhancing.
Chlamydia Trachomatis and Inflammatory Bowel Disease - a Coincidence?
Authors: Orda R , Samra Z , Levy Y , Shperber Y , Scapa E 
Published: February 2018

Serological tests of 35 patients suffering from inflammatory bowel disease were compared to those of 35 healthy controls. The tests were performed using the indirect immunoperoxidase assay. Ninety-three per cent of 15 patients with Crohn's disease had IgG antibodies against Chlamydia, compared to 26% in the control group. In the 20 patients with ulcerative colitis, 45% had IgG antibodies against Chlamydia, compared to 10% in the control group. High serum titres of IgG antibodies were found in most of the patients with inflammatory bowel disease, mainly with Crohn's disease, while weak reactions appeared in most of the controls in which antibodies were detected. These results suggest a high incidence of Chlamydia infection in the studied patients with inflammatory bowel disease, especially in those with Crohn's disease. The possible association between Chlamydia trachomatis and inflammatory bowel disease is discussed.
Pharmacocavernometry in the Assessment of Erectile Impotence
Authors: Eardley I , Vale J , Holmes S , Patel A , Kirby R S , Lumley J S P 
Published: February 2018

Thirty-three impotent men underwent pharmacocavernometry and cavernography. Ten patients had a good clinical response to 60 mg papaverine, nine had a moderate clinical response and in 14, the response was judged to be a poor one. Twelve patients had evidence of abnormal venous leakage from the corpora. Subsequent investigation with isotope phallography showed six patients to have arterial insufficiency and in three of these patients this was amenable to reconstructive vascular surgery. We conclude that pharmacocavernometry provides a useful, cheap and reliable method for the investigation of impotent men which may be performed on an outpatient basis.
Pathological Lesions of the External Auditory Meatus: A Review
Authors: Friedmann I 
Published: February 2018

A closer study of the pathology of the external auditory meatus shows that there are various nonneoplastic and neoplastic diseases of local origin which are of great clinico-pathological importance. These include Kimura's disease and angiolymphoid hyperplasia with eosinophilia; progressive necrotizing (or malignant) external otitis. Osteoma and ceruminoma are typical neoplasms of the external auditory meatus which is also the site of polypoid granulomatous or neoplastic structures arising from the middle ear cleft. These so-called ‘aural polyps’ often dismissed as of little or no diagnostic importance, may contain significant clues to a serious underlying infection or to a malignant neoplasm. Profuse bleeding may ensue on removal of such polyps. The histopathological features and their significance are described and discussed.
Open Access Exercise Electrocardiography: Does it Improve the Management of Cardiovascular Disease in the Community?
Authors: Paul V E , Sulke A N , Norris A D C 
Published: February 2018

In this study the use of exercise electrocardiography, by 47 general practitioners in South East Kent has been evaluated. Of 110 consecutive requests the majority (88%) were for diagnostic purposes, while only 7% were for prognostic assessment. Many of those referred were young or had non-cardiac chest pain and in 59% of cases the test result was unlikely to alter the clinical assessment of the probability of ischaemic heart disease (IHD). The test result influenced patient management in 85% of cases. Only 15% of patients were subsequently referred to the district general hospital although all had been considered for referral prior to the test. Although referral for invasive investigation of six patients was expedited by the provision of stress testing, in five patients general practitioners failed to consider any further investigation despite the patient having a strongly positive test. General practitioners use exercise electrocardiography primarily to exclude IHD in patients at low risk and provide reassurance. They rarely use the test as a means to guide management of those with known or probable IHD.
Long-Term Indwelling Silastic Central Venous Catheters: Clinical Audit Leading to Improved Surgical Technique
Authors: Dennis M J S , Hunter Ann E , Ryan J J 
Published: February 2018

A retrospective audit of the surgical insertion and clinical outcome of silastic venous catheters on our Haematology Unit was performed for the period 1985 to 1988. Twenty-three (58%) of the 40 lines had complications, and analysis showed that many were due to problems related to the surgical technique used. This altered our clinical practice, and over a 12 month period (January 1989 to January 1990) 26 central venous catheters have been placed in 24 patients by a dedicated surgical team using a standardized, altered technique. This has been to place all catheters via the right internal jugular vein and to confirm line position by on-table radiographic screening. A significant improvement in results is presented.
A Camera that Directly Measures Physical Parameters
Authors: Ahmed R , Vernon S A 
Published: February 2018

Accurate measurement of physical parameters is essential for the practice of modern medicine and ophthalmology in particular. A measuring device is presented that combines a single lens reflex (SLR) camera body incorporating two aligned in-camera grids with a calibrated macrozoom attachment. The device has multiple applications wherever accurate measurements are required. The ability to measure and record physical parameters in both health and disease is essential to modern medical practice. This is particularly so in ophthalmology. Despite the relative accessibility of external structures, the clinician's measuring equipment often takes the form of a clear plastic ruler with the ever present possibility of inaccuracy from parallax and perspective1. Indeed, even in the hands of expert observers, the results from the commercially produced Hertel exophthalmometer are prone to significant variation2. Various photographic methods of measurement have been described using a fixed focal length lens system3,4, and recently evaluated5. These, however, require processing of the photographs before measurements can be taken. We present a simple, relatively inexpensive multipurpose device which can measure physical parameters directly and record photographic evidence of these measurements. In essence, the device consists of a single lens reflex (SLR) camera fitted with two carefully aligned grids, linked to a calibrated macrozoom lens.
An Audit of Surgical Treatment of Ovarian Cancer in a Metropolitan Health Region
Authors: Hudson C N , Potsides P , Curling O M 
Published: February 2018

The varied application of surgery to the initial treatment of 908 cases of primary ovarian cancer is analysed. In patients with advanced disease (FIGO Stages IIb, III and IV) 256 (46%) of 555 women achieved minimal residual disease status by primary surgery and this proportion fell to 24% when only stages III and IV were considered; of these cases 7% underwent adjunctive intestinal resection or urinary tract surgery. Although not in a clinical trial situation the women achieving minimal residual disease status before chemotherapy survived better in the short term, although long-term survival remained disappointing. In early disease 3% of young women have been subjected to hysterectomy and removal of both ovaries. By contrast, in 16% of women over the age of 40 years with early ovarian cancer bilateral oophorectomy was not carried out.
Psychomotor and Clinical Assessment of Flumazenil as an Antagonist of Midazolam
Authors: Bill K M , Fee J P H , Clarke R S J 
Published: February 2018

The benzodiazepine antagonist flumazenil (0.01 mg/kg) has been compared with doxapram (1 mg/kg) and saline for the reversal of anaesthesia with intravenous midazolam, alfentanil, nitrous oxide in oxygen and isoflurane. The completeness of reversal was assessed by means of a four-choice reaction time test, 1 and 3 h following the antagonist. In addition, the level of sedation was graded using a five-point scale. Psychomotor testing showed that 60 min after administration of the antagonist, there were marked increases in reaction times (P < 0.05) both in the control and doxapram groups, but not in those receiving flumazenil. At 180 min, however, reaction times in all groups had returned to baseline values. In contrast, there was a significant difference in the sedation scores between the saline and flumazenil groups throughout the study period (P < 0.05). During the 4 h following midazolam, there was no evidence of re-sedation in any of the groups despite the relatively high midazolam dosage.
Self-Help, Mutual Aid and Chronic Patients' Clubs in Croatia, Yugoslavia: Discussion Paper
Authors: Kulčar Z 
Published: February 2018

This paper describes the clubs for patients with hypertension which have operated effectively in parts of Croatia and Slovenia (Yugoslavia) for more than 15 years, with many thousands of patients enrolling voluntarily. Based on the principle of self-help, yet involving the regular participation of members of a patient's own primary health team, they increase compliance with long-term treatment regimens and improve the quality of life. Such programmes are capable of reducing the amount of time devoted by a medical practitioner while increasing the effectiveness of treatments. If they are to succeed, it is essential to ensure regular club meetings, social activities and encouragement to each individual member to find a role and to continue attending for as long as possible. A new life style and consequent benefits to health are obtained only through long membership.