bluuebunny/crossref_metadata_2025_split huggingface dataset:
MET overexpression contributes to STAT4-PD-L1 signaling activation associated with tumor-associated, macrophages-mediated immunosuppression in primary glioblastomas
Authors: Wang Qiang-Wei , Sun Li-Hua , Zhang Ying , Wang Zheng , Zhao Zheng , Wang Zhi-Liang , Wang Kuan-Yu , Li Guan-Zhang , Xu Jian-Bao , Ren Chang-Yuan , Ma Wen-Ping , Wang Hong-Jun , Li Shou-Wei , Zhu Yong-Jian , Jiang Tao , Bao Zhao-Shi 
Published: October 2021

BackgroundDysregulated receptor tyrosine kinases, such as the mesenchymal-epidermal transition factor (MET), have pivotal role in gliomas. MET and its interaction with the tumor microenvironment have been previously implicated in secondary gliomas. However, the contribution of MET gene to tumor cells’ ability to escape immunosurveillance checkpoints in primary gliomas, especially in glioblastoma (GBM), which is a WHO grade 4 glioma with the worst overall survival, is still poorly understood.MethodsWe investigated the relationship between MET expression and glioma microenvironment by using multiomics data and aimed to understand the potential implications of MET in clinical practice through survival analysis. RNA expression data from a total of 1243 primary glioma samples (WHO grades 2–4) were assembled, incorporating The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and GSE16011 data sets.ResultsPearson’s correlation test from the three data sets indicated that MET showed a robust correlation with programmed death-ligand 1 (PD-L1) and STAT pathways. Western blot analysis revealed that in GBM cell lines (N33 and LN229), PD-L1 and phosphorylated STAT4 were upregulated by MET activation treatment with hepatocyte growth factor and were downregulated on MET suppression by PLB-1001. Tumor tissue microarray analysis indicated a positive correlation between MET and PD-L1 and macrophage-associated markers. Chromatin immunoprecipitation-PCR assay showed enrichment of STAT4 in the PD-L1 DNA. Transwell co-culture and chemotaxis assays revealed that knockdown of MET in GBM cells inhibited macrophage chemotaxis. Moreover, we performed CIBERSORTx and single-cell RNA sequencing data analysis which revealed an elevated number of macrophages in glioma samples with MET overexpression. Kaplan-Meier survival analysis indicated that activation of the MET/STAT4/PD-L1 pathway and upregulation of macrophages were associated with shorter survival time in patients with primary GBM.ConclusionsThese data indicated that the MET-STAT4-PD-L1 axis and tumor-associated macrophages might enforce glioma immune evasion and were associated with poor prognosis in GBM samples, suggesting potential clinical strategies for targeted therapy combined with immunotherapy in patients with primary GBM.
Avelumab for platinum-ineligible/refractory recurrent and/or metastatic squamous cell carcinoma of the head and neck: phase Ib results from the JAVELIN Solid Tumor trial
Authors: Guigay Joël , Lee Keun-Wook , Patel Manish R , Daste Amaury , Wong Deborah J , Goel Sanjay , Gordon Michael S , Gutierrez Martin , Balmanoukian Ani , Le Tourneau Christophe , Mita Alain , Vansteene Damien , Keilholz Ulrich , Schöffski Patrick , Grote Hans Juergen , Zhou Dongli , Bajars Marcis , Penel Nicolas 
Published: October 2021

BackgroundRecurrent and/or metastatic (R/M) disease develops in approximately 65% of patients with squamous cell carcinoma of the head and neck (SCCHN) and is associated with a poor prognosis. Immune checkpoint inhibitors have proven effective in multiple tumor types, including R/M SCCHN. We report the efficacy and safety of avelumab (antiprogrammed death ligand 1 antibody) in an expansion cohort of patients with platinum-refractory/ineligible R/M SCCHN enrolled in the phase I JAVELIN Solid Tumor trial (NCT01772004).MethodsEligible patients with R/M SCCHN were aged ≥18 years and had received ≥1 line of platinum-based chemotherapy with disease progression or recurrence within 6 months of the last dose or were ineligible for platinum-based chemotherapy. All patients received avelumab 10 mg/kg every 2 weeks. Tumor assessments were carried out by a blinded independent review committee (IRC) and investigators according to Response Evaluation Criteria in Solid Tumors V.1.1 (RECIST 1.1). Key endpoints included best overall response, duration of response (DOR) and progression-free survival (PFS) assessed by IRC and investigator per RECIST 1.1, overall survival (OS), and safety.ResultsBetween April 24, 2015, and November 13, 2015, 153 patients were enrolled. Patients had a median of two prior lines of therapy for metastatic or locally advanced disease (range 0–6); 12 patients (7.8%) were not eligible for platinum-based chemotherapy. At data cut-off (December 31, 2017), the confirmed objective response rate was 9.2% (95% CI 5.1% to 14.9%) assessed by IRC and 13.1% (95% CI 8.2% to 19.5%) assessed by investigator. Median DOR was not reached (95% CI 4.2 to not estimable) based on IRC assessment. Median PFS was 1.4 months (95% CI 1.4 to 2.6) assessed by IRC and 1.8 months (95% CI 1.4 to 2.7) assessed by investigator; median OS was 8.0 months (95% CI 6.5 to 10.2). Any-grade treatment-related adverse events (TRAEs) occurred in 83 patients (54.2%) and were grade ≥3 in 10 patients (6.5%). The most common TRAEs were fatigue (n=19, 12.4%), fever (n=14, 9.2%), pruritus (n=12, 7.8%), and chills (n=11, 7.2%), and there were no treatment-related deaths.ConclusionAvelumab showed clinical activity and was associated with a low rate of grade ≥3 TRAEs in heavily pretreated patients with platinum-refractory/ineligible R/M SCCHN.
Clinical profile of fatal familial insomnia: phenotypic variation in 129 polymorphisms and geographical regions
Authors: Zhang Jing , Chu Min , Tian ZiChen , Xie KeXin , Cui Yue , Liu Li , Meng JiaLi , Yan HaiHan , Ji Yang-Mingyue , Jiang Zhuyi , Xia Tian-Xinyu , Wang Dongxin , Wang Xin , Zhao Ye , Ye Hong , Li Junjie , Wang Lin , Wu Liyong 
Published: October 2021

ObjectiveElucidate the core clinical and genetic characteristics and identify the phenotypic variation between different regions and genotypes of fatal familial insomnia (FFI).MethodsA worldwide large sample of FFI patients from our case series and literature review diagnosed by genetic testing were collected. The prevalence of clinical symptoms and genetic profile were obtained, and then the phenotypic comparison between Asians versus non-Asians and 129Met/Met versus 129Met/Val were conducted.ResultsIn total, 131 cases were identified. The age of onset was 47.51±12.53 (range 17–76) years, 106 patients died and disease duration was 13.20±9.04 (range 2–48) months. Insomnia (87.0%) and rapidly progressive dementia (RPD; 83.2%) occurred with the highest frequency. Hypertension (33.6%) was considered to be an objective indicator of autonomic dysfunction. Genotype frequency at codon 129 was Met/Met (84.7%) and Met/Val (15.3%), and allele frequency was Met (92.4%) and Val (7.6%).129 Met was a risk factor (OR: 3.728, 95% CI: 2.194 to 6.333, p=0.000) for FFI in the non-Asian population. Comparison of Asians and non-Asians revealed clinical symptoms and genetic background to show some differences (p<0.05). In the comparison of 129 polymorphisms, a longer disease duration was found in the 129 MV group, with alleviation of some clinical symptoms (p<0.05). After considering survival probability, significant differences in survival time between genotypes remained (p<0.0001).ConclusionsInsomnia, RPD and hypertension are representative key clinical presentations of FFI. Phenotypic variations in genotypes and geographic regions were documented. Prion protein gene 129 Met was considered to be a risk factor for FFI in the non-Asian population, and 129 polymorphisms could modify survival duration.
Sensitivity of brain MRI and neurological examination for detection of upper motor neurone degeneration in amyotrophic lateral sclerosis
Authors: Nitert Abram D , Tan Harold HG , Walhout Renée , Knijnenburg Nienke L , van Es Michael A , Veldink Jan H , Hendrikse Jeroen , Westeneng Henk-Jan , van den Berg Leonard H 
Published: October 2021

ObjectivesTo investigate sensitivity of brain MRI and neurological examination for detection of upper motor neuron (UMN) degeneration in patients with amyotrophic lateral sclerosis (ALS).MethodsWe studied 192 patients with ALS and 314 controls longitudinally. All patients visited our centre twice and underwent full neurological examination and brain MRI. At each visit, we assessed UMN degeneration by measuring motor cortex thickness (CT) and pyramidal tract fibre density (FD) corresponding to five body regions (bulbar region and limbs). For each body region, we measured degree of clinical UMN and lower motor neuron (LMN) symptom burden using a validated scoring system.ResultsWe found deterioration over time of CT of motor regions (p≤0.0081) and progression of UMN signs of bulbar region and left arm (p≤0.04). FD was discriminative between controls and patients with moderate/severe UMN signs (all regions, p≤0.034), but did not change longitudinally. Higher clinical UMN burden correlated with reduced CT, but not lower FD, for the bulbar region (p=2.2×10−10) and legs (p≤0.025). In the arms, we found that severe LMN signs may reduce the detectability of UMN signs (p≤0.043). With MRI, UMN degeneration was detectable before UMN signs became clinically evident (CT: p=1.1×10−10, FD: p=6.3×10−4). Motor CT, but not FD, deteriorated more than UMN signs during the study period.ConclusionsMotor CT is a more sensitive measure of UMN degeneration than UMN signs. Motor CT and pyramidal tract FD are discriminative between patients and controls. Brain MRI can monitor UMN degeneration before signs become clinically evident. These findings promote MRI as a potential biomarker for UMN progression in clinical trials in ALS.
Leptospirosis. Do you consider the diagnosis?
Authors: Rudland S. V. 
Published: October 2021

AbstractPatients with Leptospirosis, usually a water borne zoonotic disease, are likely to present themselves to Royal Naval primary health carers, who deal with a young active population, frequently participating in watersports.Leptospira, which belong to the order Spirochaetaceae, comprise of two distinct species. Within each species there are a number of serologically different serovars (serotypes), arranged in related serogroups.L. interrogans var Icterohaemorrhagiae and L. interrogans var Hebdomadis serovar hardjo are the most commonly reported organisms in Great Britain. Traditionally water and sewage workers have been amongst those most frequently infected, but with improved health care awareness this group has been overtaken by farmworkers, and a growing group of people engaged in aquatic sports.Symptoms of Leptospiral infection vary in severity from a mild flu-like illness to symptoms resulting from severe renal, hepatic or meningeal involvement.Mild symptoms respond to oral penicillin, erythromycin or tetracyclines, whilst more serious illness requires i.v. penicillin and supportive nursing. Spirochaetes can be detected in culture using darkground microscopy, and sero-conversion detected by IgM specific dot ELISA techniques. Suspected sera should be sent to PHLS Leptospira Reference Unit, County Hospital, Hereford. HR1 2ER. (Tel: 0432 277117).
Experiences with ureteroscopy
Authors: Spalding T. J. W. 
Published: October 2021

AbstractThirty-nine patients underwent 44 ureteroscopic procedures between January 1985 and August 1988 for diagnostic and therapeutic purposes. Twenty six procedures were undertaken on 23 patients for extraction of ureteric calculi and were successful on the initial attempt in 14 (61%). Four stones not removed on the first attempt were however disimpacted and subsequently passed spontaneously, and three more were removed at a second ureteroscopy. The overall success rate therefore was 91%. Only two patients required ureterolithotomy.Ureteroscopic stone extraction is therefore an effective technique with minimal morbidity and allows rapid return of servicemen to high category medical fitness.
Space Motion Sickness
Authors: Pingree B. J. W. 
Published: October 2021

AbstractSpace Motion Sickness (SMS) is the malady which frequently occurs shortly after attainment of sustained exposure to hypogravity. It is characterised by a variety of symptoms, which may proceed to nausea and eventually vomiting. Natural adaptation usually occurs if exposure to hypogravity is maintained. The condition appears to be the manifestation of motion sickness that is specific to hypogravity. It is associated with otolith-canal and otolith-eye conflict. SMS may have operational significance in impairing the performance of spacecraft crews. The condition is likely to be amenable to treatment with anti-motion sickness drugs. It may be possible to reduce any operational effects of SMS by suitable crew selection and training procedures.
The Effect of Clothing on the initial Responses to Cold Water Immersion in man
Authors: Tipton M. J. , Stubbs D. A. , Elliott D. H. 
Published: October 2021

AbstractThe protection provided by three clothing assemblies against the cold shock response was investigated. Nine healthy male volunteers each undertook three two minute head-out immersions into stirred water at 10°C. The subjects wore a different clothing assembly for each immersion, these were:
(a)Swimming trunks only;(b)Conventional clothing (equivalent to RN No 8s);(c)Conventional clothing plus windproof/showerproof clothing (RN foul-weather clothing Mk III).The cardiac, ventilatory and thermal responses of the subjects were examined before and during the immersions.No significant differences were found between the magnitude of the responses recorded on immersion when conventional clothing or foul-weather clothing were worn. Mean skin temperature was lower (P<0.05) and respiratory frequency and minute ventilation were higher (P<0.05) on immersion in swimming trunks compared to the other two conditions.It is concluded that when policies for the use of immersion protective clothing are being formulated, consideration should be given to all of the potentially hazardous responses associated with cold water immersion.
Ventilation with isoflurane in the Triservice anaesthetic apparatus: a comparison with halothane and trichlorethylene
Authors: Roberts D. R. D. , Pethybridge R. J. 
Published: October 2021

AbstractRecovery from anaesthesia using the Triservice anaesthetic apparatus with either isoflurane alone or halothane and trichlorethylene, was assessed by measurement of reaction time. There was no statistically significant improvement in recovery between patients who received low concentrations of isoflurane and those who received halothane and trichlorethylene.The mean profiles of systolic pressure and heart rate were significantly greater in the isoflurane group (P<0.05) than in the halothane/trichlorethylene group. Cardiovascular stability was maintained into the recovery period. The benefits of low concentrations of isoflurane as sole agent in the Triservice anaesthetic apparatus and their extrapolation to a shocked casualty in a military setting are discussed.
The hazards of operational diving in heavily oil-polluted water
Authors: Peterson K. A. , Portouw S. J. 
Published: October 2021

AbstractThe war in the Gulf and the resultant massive oil spill has prompted an assessment of the health hazards to naval divers operating in oil-fouled environments. A review of current literature and discussions with experts in the field was undertaken to assess these hazards. With the assistance of Kuwait Petroleum, an assay of the content of average Kuwait crude was obtained. The risks of contact with crude oil and its vapours via the skin, inhalation and ingestion have been assessed. Contact dermatitis is the most likely sequel. A chemical pneumonitis from oil inhalation is possible but extremely unlikely. A health risk from ingestion of crude oil is equally unlikely since no toxic effect is thought to occur below a consumption of 5 ml/kg (350 ml for an average diver). Trace metals were found to be at a level of less than 1/10 of the minimal toxic dose for all but vanadium. No increased risk of skin cancer can be found in animal studies of crude oil. Epidemiological studies have recorded no increased risk of bladder or thyroid cancer in petroleum workers, but an increase in lung, nasal cavity, sinus and skin cancer has been shown following chronic exposure to low levels of petroleum vapour. No medical indication was found for modification of existing operational procedures, although, since the toxicity of some components of crude oil is unknown, the use of improved equipment to avoid contact should be studied.
Laryngeal mask airway and tracheal tube insertion by unskilled personnel
Authors: Davies P. R. F. , Tighe S. Q. M. , Greenslade G. L. , Evans G. H. 
Published: October 2021

AbstractAfter a short training programme 11 naval medical trainees inserted a laryngeal mask airway (LMA) and a tracheal tube (ETT) in random order in a total of 110 anaesthetized patients. They were allowed 40 seconds for each attempt. Success was defined as the detection of expired carbon dioxide within 40 seconds of Guedel airway removal which subsequently rose to an end-tidal value of at least 4 kPa, together with satisfactory lung expansion and ventilation, without other airway intervention by the anaesthetist. One hundred and four LMA insertions were successful compared with 56 ETTs (p<0.01). All first attempts at LMA insertion were successful, whereas satisfactory ETT placement was progressive. Insertion was also quicker with the LMA (20 seconds) than with the ETT (35 seconds) (p<0.01). Further studies are indicated to assess the value of the LMA in emergencies.
Medical audit: A Well Woman Clinic in the Royal Naval training practice, Gibraltar
Authors: Westwood P. R. 
Published: October 2021

AbstractIn order to assess the effectiveness of patient self-selection, and the value of dedicating surgery time to a specific clinic, attendances at a Well Woman Clinic were compared with attendances for the same reasons at other times. During the nine month audit period the opportunity was also taken to overhaul the Age/Sex Register, and assess the uptake of Cervical Screening at the Garrison Medical Centre. This unit is part of the Royal Naval Training Practice in Gibraltar.
Advanced Trauma Life Support aboard RFA Argus
Authors: Greenslade G. L. , Taylor R. H. 
Published: October 2021

SummaryThe Advanced Trauma Life Support (ATLS) system was adopted for casualty reception and resuscitation. ATLS permitted well-informed triage decisions to be made, coupled with appropriate initial, possibly life-saving, treatment. The training given on board has continued to benefit patients treated by ex-Argus staff in their peacetime roles.
Primary Casualty Reception Ship: the hospital within—Operation Granby
Authors: Dewar E. P. 
Published: October 2021

SummaryAs the build-up of Operation Granby forces developed in the Gulf, casualty estimates indicated the need for a 100-bed hospital facility to care for the possible maritime casualties. RFA Argus, the Air Training Ship, was identified as the potential Primary Casualty Reception Ship (PCRS) and at the end of September 1990 plans were drawn up to convert the forward hangar into a two-storey 100-bed hospital in collective protection (COLPRO).In the three weeks prior to deployment, the hospital was designed, built, equipped and staffed.Argus arrived in the Gulf in mid-November as the PCRS with, all in COLPRO, a 10-bed intensive care unit (ICU), a 14-bed high dependency unit (HDU), a 76-bed low dependency unit (LDU) plus four operating tables in two theatres with full support services.The hospital was staffed by a medical team of 136 personnel and supported by the Air department with four casualty evacuation helicopters, an RN Party and the staff of the RFA.One hundred and five patients were treated of which 78 were returned to duty. Argus as PCRS spent longer in the northern Persian Gulf than any other ship, UK or US.
Immersion fatalities: Hazardous responses and dangerous discrepancies
Authors: Tipton M. J. 
Published: October 2021

AbstractIn this paper the following question is addressed: ‘Why, given the plethora of standards, specifications and guidelines for immersion protective equipment, are lives still being lost at sea and fatal accident enquiries questioning the quality of such equipment?’In attempting to answer this question, consideration is given to the extent to which both the possible prevailing environmental conditions, and the physiological responses they evoke, are recognised in the design, selection and evaluation of immersion protective equipment. The hazardous responses associated with immersion in cold water are briefly reviewed and the value and relevance of some of the existing tests of immersion protective clothing are considered.It is concluded that: i. when standards, policies and tests for the selection and use of immersion protective clothing are being formulated, consideration should be given to all of the hazardous responses associated with immersion; ii. it should be recognised that the performance of immersion protective equipment during an accident may be significantly inferior to that predicted by routine testing for certification.
Repeated pseudo-obstruction, mental subnormality – and serious snags
Authors: Guy R. J. , Barker C. P. G. 
Published: October 2021

SummaryChronic intestinal pseudo-obstruction has certain identifiable causes but many cases remain idiopathic. The majority of patients are managed successfully by conservative means with the avoidance of surgery. A case is presented where diagnosis was made difficult by autism and which was complicated by perforation of a gastric ulcer. Management of pseudo-obstruction is discussed and emphasis placed on an awareness of alternative life-threatening pathologies at re-presentation.
Investigating Gulf Veterans’ Health Concerns
Authors: Graham J. T. 
Published: October 2021

AbstractIn order to answer the questions arising from the health concerns of Gulf veterans, the Defence Medical Services have collated relevant health data so that they may be systematically analysed. However, data coverage is limited and there are concerns about its quality. Intramural studies alone will not be robust enough to determine if veterans are experiencing an excess of ill-health so a programme of epidemiological studies will be commissioned in collaboration with the Medical Research Council.
Fortune favours the Brave - The Capture of Guadeloupe 1815
Authors: Agnew R. A. L. 
Published: October 2021

AbstractIn August 1815, Sir Philip Durham and Sir James Leith, with the help of the French Royalist Comte de Vaugiraud from Martinique, landed a body of troops on the island of Guadeloupe. After a skirmish, in which the British army lost 16 killed and about 50 wounded, the Comte Linois struck his flag and surrendered the island. Afterwards he was, along with his adjutant-general, conveyed to France under the terms of the articles of the capitulation treaty. The Commander in Chief of the Leeward Islands Squadron at that time, Admiral Sir Philip Durham KCB, and his Secretary, Surgeon John Forbes, played important roles in the recapture of the island.