bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting human leukocyte antigen G with chimeric antigen receptors of natural killer cells convert immunosuppression to ablate solid tumors
Authors: Jan Chia-Ing , Huang Shi-Wei , Canoll Peter , Bruce Jeffrey N , Lin Yu-Chuan , Pan Chih-Ming , Lu Hsin-Man , Chiu Shao-Chih , Cho Der-Yang 
Published: October 2021

BackgroundImmunotherapy against solid tumors has long been hampered by the development of immunosuppressive tumor microenvironment, and the lack of a specific tumor-associated antigen that could be targeted in different kinds of solid tumors. Human leukocyte antigen G (HLA-G) is an immune checkpoint protein (ICP) that is neoexpressed in most tumor cells as a way to evade immune attack and has been recently demonstrated as a useful target for chimeric antigen receptor (CAR)-T therapy of leukemia by in vitro studies. Here, we design and test for targeting HLA-G in solid tumors using a CAR strategy.MethodsWe developed a novel CAR strategy using natural killer (NK) cell as effector cells, featuring enhanced cytolytic effect via DAP12-based intracellular signal amplification. A single-chain variable fragment (scFv) against HLA-G is designed as the targeting moiety, and the construct is tested both in vitro and in vivo on four different solid tumor models. We also evaluated the synergy of this anti-HLA-G CAR-NK strategy with low-dose chemotherapy as combination therapy.ResultsHLA-G CAR-transduced NK cells present effective cytolysis of breast, brain, pancreatic, and ovarian cancer cells in vitro, as well as reduced xenograft tumor growth with extended median survival in orthotopic mouse models. In tumor coculture assays, the anti-HLA-G scFv moiety promotes Syk/Zap70 activation of NK cells, suggesting reversal of the HLA-G-mediated immunosuppression and hence restoration of native NK cytolytic functions. Tumor expression of HLA-G can be further induced using low-dose chemotherapy, which when combined with anti-HLA-G CAR-NK results in extensive tumor ablation both in vitro and in vivo. This upregulation of tumor HLA-G involves inhibition of DNMT1 and demethylation of transporter associated with antigen processing 1 promoter.ConclusionsOur novel CAR-NK strategy exploits the dual nature of HLA-G as both a tumor-associated neoantigen and an ICP to counteract tumor spread. Further ablation of tumors can be boosted when combined with administration of chemotherapeutic agents in clinical use. The readiness of this novel strategy envisions a wide applicability in treating solid tumors.
Influenza B, Q Fever and the consequences of febrile illness occurring during Jungle Warfare Training: a clinical and serological study
Authors: Wale M. C. J. 
Published: October 2021

AbstractSeventy-one Royal Marines undergoing jungle warfare training were studied clinically and serologically to determine the incidence and consequences of febrile illness. During acclimatisation and the early part of the deployment the incidence of illness having an impact on training was low; during the latter part an outbreak of influenza B occurred, with 25 cases diagnosed clinically. Only 12 of these were confirmed serogically, probably because the outbreak was still in progress when the second samples were taken. A further four subclinical cases were uncovered by the serological study.Five cases of heat exhaustion occurred, one Marine suffering two episodes. Four patients required casevac from the jungle. Three Marines were found to have serological evidence of previous acute Q fever, including the patient who had two episodes of heat exhaustion. This incidence is higher than expected, and warrants further investigation.
Von Recklinghausen’s disease of nerves: A modern day social response
Authors: Hett D. A. , Mather S. , Dewar E. P. 
Published: October 2021

AbstractWe describe a patient with von Recklinghausen’s Disease of Nerves whose appearance provoked an emotive reaction in the close community of an RN ship akin to that reported in the case of Sir Frederick Treves’ “Elephant Man”. The RN divisional system provided a valuable contribution to the resolution of the problems created.
Meningioma as an incidental finding in an intensive care unit
Authors: Tighe S. Q. M. , Turner G. A. 
Published: October 2021

SummaryA report on two hypotensive episodes secondary to post-operative haemorrhage is presented. Recovery was complicated by prolonged coma and a frontal meningioma was eventually discovered. The possible aetiology of this coma is discussed. Intracranial pathology should be suspected when coma persists on the intensive care unit.
Changing trends in dental restorative treatment needs of Naval Recruits 1987–1989—Disease or Diagnosis?
Authors: Alexander D. C. C. , Pethybridge R. J. 
Published: October 2021

AbstractThe restorative treatment needs of 9960 young men and women who entered the Naval Service at HMS Raleigh between January 1987 and April 1989 are summarised. A marked increase in the numbers of fillings required and a decrease in the proportion considered to be dentally fit occurred in May 1988 and has continued as a trend thereafter. Weighted non-orthogonal analysis of variances have been conducted to assess the significance of clinical and period variables upon the changes.
The diary of Assistant Surgeon Henry Piers, HMS Investigator, 1850–54
Authors: Savours Ann M. 
Published: October 2021

SummaryFrom the 16th to the mid 19th century, many voyages were made from England to discover a North West Passage between the Atlantic and the Pacific oceans. The Investigator was one of some 40 vessels that searched for the lost North West Passage expedition of 1845–48 under the command of Sir John Franklin in HM Ships Erebus and Terror, which became beset among what are now known as the Canadian Arctic Islands. The “Investigators” found no trace of Franklin, but were the first to traverse the North West Passage, although their ship had to be abandoned in Mercy Bay on Banks Island after two winters there. The diary of Assistant Surgeon Henry Piers, from the manuscript collection of the National Maritime Museum, Greenwich, is here examined. Reference is also made to the narrative and report published by the senior surgeon of the Investigator, Dr Alexander Armstrong.
Operating at Sea in an Aircraft Carrier
Authors: Hett D. A. , Dewar E. P. 
Published: October 2021

SummaryThe policy of the Medical Officers serving in HMS Ark Royal between January 1988 and June 1989 with regard to surgery and anaesthesia at sea is described.The skills and equipment available, techniques used, operations performed and complications that resulted are outlined.The advantages and disadvantages of an active operating policy are discussed and the postulate ventured that in order to achieve maximum efficiency within the medical department of an aircraft carrier such a policy is justified.Finally, in the light of present day litigious trends, the question of the propriety of the policy is posed.
NBCI—Another threat to Operational Effectiveness?
Authors: Dewar E. P. , Taylor R. B. , Jones J. , Hett D. A. 
Published: October 2021

AbstractBattle casualties are well recognised as a threat to Operational Effectiveness (OE) at times of conflict. Less well appreciated is that naturally occurring illnesses and injuries—Non-Battle Casualties and Injuries (NBCI)—continue to present at such times and will add to the problems of fighting the ship. This prospective study showed that NBCI resulted in a total of 1369 man days of lost personnel effectiveness among some 1738 RN servicemen during a 180 day deployment. That is just 0.42% of the possible man working days. This represents a loss of 4.3 man days per 1000 at risk per day in terms of fitness for Full Duties or 2.74/1000/day excluding those able to perform Light Duties. It is unlikely that such rates would affect the OE of the fighting units but they do represent a significant challenge to the Royal Naval Medical Service to continue to maintain the rates at such low levels, so that when aggregated to the numbers of battle casualties, OE is maintained as far as possible.
Haematological and biochemical screening of potential Royal Naval aircrew
Authors: Sheard S. C. 
Published: October 2021

AbstractThe objective of this study was to determine which, if any, of a small range of haematological and biological tests would be of value in detecting disease risk factors as an addition to the Initial Flying Medical when screening potential Royal Naval aircrew. A retrospective review of results of haematological and biochemical profiles of 200 candidates screened at the Central Air Medical Board was used. Ninety nine candidates (49.5%) were found to have profiles outside the normal range on initial testing. Many of these were found to be normal on repeat testing or further investigation. One candidate was made permanently unfit to fly and three others had certain conditions put on their training or careers. It is concluded that most of the screening carried out serves only a limited function. It is recommended that screening should be stopped; however, should screening still be considered necessary only four tests are required, ie, fasting blood glucose, fasting total cholesterol and triglycerides, liver function test and full blood count.
The retrograde tunnel: a method for the fixation of central venous catheters in the military environment
Authors: Wheeler R. A. , Spalding T. J. W. , Thomas J. A. , Carss G. A. 
Published: October 2021

AbstractCentral venous catheters (CVCs) are prone to accidental removal during patient transportation. Of the casualties who require transfer between medical facilities, those with CVC in situ require additional vigilance to prevent loss of the CVC, which continues to occur despite various methods of fixation. The fashioning of a subcutaneous tunnel has become an integral part of the placement of central venous catheters. Several methods have been described, but the long-term CVCs in paediatric practice pose special problems, particularly that of the patients continually testing the CVCs fixation. Using a new polyurethane CVC, a retrograde tunnelling technique has been developed which affords immediate and secure fixation. We propose that this CVC, together with the technique of retrograde tunnelling, is the solution to inadvertent central venous line removal during patient transfer.
Changes in selected parameters of health and physical fitness following a sixteen-week deployment at sea
Authors: King-Lewis P. W. , Allsopp A. J. 
Published: October 2021

AbstractThe effects of 16 weeks at sea upon selected parameters of health and physical fitness were investigated in 30 male volunteers (from a total crew of 48 men) prior to, and immediately following deployment.The 30 subjects were assigned to either an exercise group, ‘Ex’ (n=12), or a non-exercising group, ‘Nilex’ (n=18), according to their reported participation in vigorous training or sports.Body mass index (BMI), calculated from height and weight, revealed that prior to deployment 13 of the 30 subjects (two in the Ex group) had a BMI over 25 kg.m−2 (i.e. overweight), and a further three subjects (all ‘non-exercisers’) had values of 30 kg.m−2 or more (obese). In addition, the diastolic blood pressure of two subjects was in excess of 95 mmHg and five subjects had resting heart rates above 89 beats per minute. Retrospective comparisons between the Ex and Nilex groups revealed a significantly lower percentage body fat (P<0.01) and a faster rate of cardiac recovery (P<0.05) following a standardised bout of exercise in the Ex group, albeit that these individuals were significantly younger (mean age of 24 years) than those in the Nilex group (32 years).Following deployment, in the Nilex group, comparison of pre- and post values showed that resting heart rate was elevated (P<0.01) on return from sea. Similarly, in the Nilex group heart rate while performing the standardised exercise about was also elevated (P<0.05) on the second test occasion. In the Ex group, heart rate measures during and following exercise indicated a significantly slower rate of recovery (P<0.05) on the second test occasion.It is concluded that: firstly, these rudimentary measures suggest a poor level of physical fitness among some members of the crew who reported not to take regular physical exercise; secondly, changes in cardiac responses to exercise consistent with a reduction in cardiovascular fitness were observed following the 16 week deployment.
Medicine and the Master′s Degree Business Administration
Authors: James C. M. 
Published: October 2021

AbstractThis article provides a personal view of the Masters Degree in Business Administration (MBA) and its utility for a clinician. It outlines the principles behind the course and describes the details of one MBA provider, the Open Business School. Four examples are used to illustrate the value of the qualification and some conclusions are drawn as to its usefulness in modern healthcare.
Tuberculous epididymitis presenting as acute hydrocele
Authors: Guy R. J. 
Published: October 2021

Abstract>A case of tuberculous epididymitis which presented as an acute hydrocele is reported and the relevant literature reviewed. The patient had undergone contralateral orchidectomy 20 years previously for the same condition associated with pulmonary tuberculosis. The most recent episode followed unrelated illness; the diagnosis was confirmed after surgical intervention and cure was achieved with adjuvant chemotherapy. Although rare, genital tuberculosis should still be considered in cases of scrotal swelling when there is a history of previous tuberculous disease or exposure.
Rationale and design of the preserved versus reduced ejection fraction biomarker registry and precision medicine database for ambulatory patients with heart failure (PREFER-HF) study
Authors: Abboud Andrew , Nguonly Austin , Bean Asher , Brown Kemar J , Chen Roy F , Dudzinski David , Fiseha Neyat , Joice Melvin , Kimaiyo Davis , Martin Mackenzie , Taylor Christy , Wei Kevin , Welch Megan , Zlotoff Daniel A , Januzzi James L , Gaggin Hanna K 
Published: October 2021

IntroductionPatients with heart failure (HF) are classically categorised by left ventricular ejection fraction (LVEF). Efforts to predict outcomes and response to specific therapy among LVEF-based groups may be suboptimal, in part due to the underlying heterogeneity within clinical HF phenotypes. A multidimensional characterisation of ambulatory patients with and without HF across LVEF groups is needed to better understand and manage patients with HF in a more precise manner.Methods and analysisTo date, the first cohort of 1313 out of total planned 3000 patients with and without HF has been enroled in this single-centre, longitudinal observational cohort study. Baseline and 1-year follow-up blood samples and clinical characteristics, the presence and duration of comorbidities, serial laboratory, echocardiographic data and images and therapy information will be obtained. HF diagnosis, aetiology of disease, symptom onset and clinical outcomes at 1 and 5 years will be adjudicated by a team of clinicians. Clinical outcomes of interest include all-cause mortality, cardiovascular mortality, all-cause hospitalisation, cardiovascular hospitalisation, HF hospitalisation, right-sided HF and acute kidney injury. Results from the Preserved versus Reduced Ejection Fraction Biomarker Registry and Precision Medicine Database for Ambulatory Patients with Heart Failure (PREFER-HF) trial will examine longitudinal clinical characteristics, proteomic, metabolomic, genomic and imaging data to better understand HF phenotypes, with the ultimate goal of improving precision medicine and clinical outcomes for patients with HF.Ethics and disseminationInformation gathered in this research will be published in peer-reviewed journals. Written informed consent for PREFER-HF was obtained from all participants. All study procedures were approved by the Mass General Brigham Institutional Review Board in Boston, Massachusetts and performed in accordance with the Declaration of Helsinki (Protocol Number: 2016P000339).Trial registration numberPREFER-HF ClinicalTrials.gov identifier:NCT03480633.
Long-term follow-up and sex differences in adults operated for tetralogy of Fallot
Authors: Quattrone Alessia , Lie Oyvind H , Nestaas Eirik , de Lange Charlotte , Try Kirsti , Lindberg Harald L , Skulstad Helge , Erikssen Gunnar , Edvardsen Thor , Haugaa Kristina , Estensen Mette E 
Published: October 2021

ObjectiveAdults operated for tetralogy of Fallot (TOF) have high risk of ventricular arrhythmias (VA). QRS duration >180 ms is an established risk factor for VA. We aimed to investigate heart function, prevalence of arrhythmias and sex differences in patients with TOF at long-term follow-up.MethodsWe included TOF-operated patients≥18 years from our centre’s registry. We reviewed medical records and the most recent echocardiographic exam. VA was recorded on ECGs, 24-hour Holter registrations and from implantable cardioverter defibrillator.ResultsWe included 148 patients (age 37±10 years). Left ventricular global longitudinal strain (LV GLS, −15.8±3.1% vs −18.8±3.2%, p=0.001) and right ventricular (RV) GLS (−15.8±3.9% vs −19.1±4.1%, p=0.001) were lower in men at all ages compared with women. Higher RV D1 (4.3±0.5 cm vs 4.6±0.6 cm, p=0.01), lower ejection fraction (55%±8% vs 50%±9%, p=0.02), lower RV GLS (−18.1±4.0 ms vs −16.1±4.8 ms, p=0.04) and N-terminal pro-brain natriuretic peptide (NT-proBNP) over reference range (n=27 (23%) vs n=8 (77%), p<0.001) were associated with higher incidence of VA. QRS duration was longer in men (151±30 ms vs 128±25 ms, p<0.001). No patients had QRS duration >180 ms. QRS duration did not differ in those with and without VA (143±32 ms vs 137±28 ms, p=0.06).ConclusionsOur results confirmed reduced RV function in adults operated for TOF. Male patients had impaired LV and RV function expressed by lower LV and RV GLS values at all ages. Reduced cardiac function and elevated NT-proBNP were associated with higher incidence of VA and may be important in risk assessment.
Effect of cigarette smoking on smoking biomarkers, blood pressure and blood lipid levels among Sri Lankan male smokers
Authors: Herath Prasanna , Wimalasekera Savithri , Amarasekara Thamara , Fernando Manoj , Turale Sue 
Published: October 2021

AbstractStudy purposeThe aim of this study was to determine the fractional exhaled nitric oxide (FeNO) levels, exhaled breath carbon monoxide (eCO) levels, blood pressure, blood lipid levels between smokers and non-smokers and to determine the association of smoking intensity with the above parameters.MethodsThis descriptive study was conducted in selected periurban areas of the Colombo District, Sri Lanka. Adult male current tobacco smokers (n=360), aged between 21 and 60 years were studied and compared with anthropometrically matched male non-smokers (n=180). Data were collected by interviewer-administered questionnaire, clinical assessment and measurement of FeNO by FENO monitor and eCO by Smokerlyser.ResultsSmokers had significantly lower mean FeNO levels and higher mean eCO values compared with non-smokers. Presentation of palpitations was higher among the smokers and a significantly positive correlation was identified between palpitations and eCO levels. There was a significantly positive correlation between the systolic blood pressure of smokers with the duration of smoking (DS), Brinkman Index (BI), Body Mass Index (BMI) and there was a significantly negative correlation with FeNO levels. The mean arterial pressure was positively correlated with the DS, BI and BMI. There was a significantly negative correlation between FeNO and the number of cigarettes smoked per day, DS and BI of smokers. Significantly higher total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), very LDL-C, TC: HDL ratio and low high density lipoprotein cholesterol (HDL-C) level was observed among smokers compared with the non-smokers.ConclusionsTobacco smoking was found to impact blood pressure and serum lipid levels thus enhancing the cardiovascular risk among smokers. The levels of eCO and FeNO are useful biomarkers for determining the intensity of smoking. The results indicate the necessity for urgent measures to stop cigarette smoking in Sri Lanka.
Cardiovascular outcomes in systemic sclerosis with abnormal cardiovascular MRI and serum cardiac biomarkers
Authors: Dumitru Raluca B , Bissell Lesley-Anne , Erhayiem Bara , Kidambi Ananth , Dumitru Ana-Maria H , Fent Graham , Abignano Giuseppina , Donica Helena , Burska Agata , Greenwood John P , Biglands John , Schlosshan Dominik , del Galdo Francesco , Plein Sven , Buch Maya H 
Published: October 2021

ObjectivesTo explore the prognostic value of subclinical cardiovascular (CV) imaging measures and serum cardiac biomarkers in systemic sclerosis (SSc) for the development of CV outcomes of primary heart involvement (pHI).MethodsPatients with SSc with no clinical SSc-pHI and no history of heart disease underwent cardiovascular magnetic resonance (CMR) imaging, and measurement of serum high-sensitivity-troponin I (hs-TnI) and N-terminal-pro-brain natriuretic peptide (NT-proBNP). Follow-up clinical and CV outcome data were recorded. CV outcomes were defined as myocarditis, arrhythmia and/or echocardiographic functional impairment including systolic dysfunction and/or diastolic dysfunction.ResultsSeventy-four patients with a median (IQR) age of 57 (49, 63) years, 32% diffuse cutaneous SSc, 39% interstitial lung disease, 30% Scl70+ were followed up for median (IQR) 22 (15, 54) months. Ten patients developed CV outcomes, comprising one patient with myocarditis and systolic dysfunction and nine arrhythmias: three non-sustained ventricular tachycardia and six supraventricular arrhythmias. The probability of CV outcomes was considerably higher in those with NT-proBNP >125 pg/mL versus normal NT-proBNP (X2=4.47, p=0.035). Trend for poorer time-to-event was noted in those with higher extracellular volume (ECV; indicating diffuse fibrosis) and hs-TnI levels versus those with normal values (X2=2.659, p=0.103; X2=2.530, p=0.112, respectively). In a predictive model, NT-proBNP >125 pg/mL associated with CV outcomes (OR=5.335, p=0.040), with a trend observed for ECV >29% (OR=4.347, p=0.073).ConclusionThese data indicate standard serum cardiac biomarkers (notably NT-proBNP) and CMR indices of myocardial fibrosis associate with adverse CV outcomes in SSc. This forms the basis to develop a prognostic model in larger, longitudinal studies.