bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of Heat Strain by Immersing the Hands and Forearms in Water
Authors: House J. R. , Holmes Cathy , Allsopp A. J. 
Published: October 2021

AbstractThe effectiveness of hand immersion in water at 10°C, 20°C and 30°C as a technique for reducing heat strain in Royal Navy (RN) personnel has been investigated at the Institute of Naval Medicine (INM). Four subjects exercised at a moderate work rate, whilst wearing fire fighting clothing in an environmental chamber at 40°C. The subjects reached heat strain safety limits within 45 minutes of commencing work at which point they rested in the heat for 30 minutes whilst they underwent one of four experimental conditions: without intervention (control); or with their hands immersed in water at 10°C, 20°C or 30°C. The experiment was repeated on a further three days so that the subjects undertook each experimental condition in a balanced randomised order. During the control condition without hand immersion the subjects were unable to cool. Immersion of the hands in water (at 10°C, 20°C or 30°C) significantly (P<0.05) lowered body core (auditory canal) temperature within ten minutes. Assessing the effectiveness of this technique by the initial rates of core temperature reduction, revealed that immersion of the hands was more effective the colder the water. Following 20 minutes of hand immersion mean core temperature had dropped from 38.5C to: 36.9(standard deviation 0.19)°C, 37.3(0.18)°C, and 37.8(0.10)°C, in 10°C, 20°C and 30°C water respectively. Cooling powers estimated from changes in mean body temperature were 334, 307 and 113 watts using 10°C, 20°C and 30°C water respectively. These results indicate that hand immersion in water at a temperature of between 10°C and 30°C is an efficient means of cooling heat stressed personnel who have been exercising. This simple and effective technique may be applied to many industrial and military tasks to reduce heat strain, lower the risk of heat injury, and increase safe total work times in the heat. For the RN, hand immersion could be used in fire fighting, damage control and NBC operations where personnel alternately work and rest.
Aeromedical evacuation in Bosnia
Authors: Dashfield A. K. , Smith H. R. , Young P. C. 
Published: October 2021

AbstractThe objective of this study was to assess the value of aeromedical evacuation when compared to road ambulance transportation in predominantly trauma patients in a rural area. Uniquely, trauma was the most common presenting condition (75%), distances to secondary care facilities were long and road routes were poor with a risk of being mined. Data were collected of all British aeromedical flights in Multi-National Division Southwest, Bosnia-Herzegovina, over a six-month period, and benefit to the patient was assessed by a panel of experts when compared to calculated road ambulance evacuation. Sixty-nine patients were evacuated by air on 57 flights and transported to a secondary care facility for further management. The panel of experts found that only 15 of the 69 patients (22%) had benefited from aeromedical evacuation. This study again shows the low benefit to the patient from indiscriminate use of aeromedical evacuation, despite the air ambulance being operated in apparently ideal conditions of a high percentage of trauma, a rural setting and poor road communications. Crew safety and the high costs further highlight the need to devise a system that can screen out unnecessary flights and identify those patients who would benefit most.
The protective effect of apelin-13 on cardiorenal toxicity induced by cyclophosphamide
Authors: Kutlay Özden , Aktan Arzu Keskin , Aslan Esra 
Published: October 2021

Cyclophosphamide is a chemotherapeutic drug that is widely used in the clinic and can cause multi-organ toxicity. Apelin-13 is an endogenous adipocytokine with antioxidant properties. Therefore, this study investigated the possibility of apelin-13 being a potential therapeutic agent on cardiac toxicity and nephrotoxicity caused by cyclophosphamide. In this study, a total of four groups were formed with eight rats in each group. Group I: the control group was administered only saline (i.p.). Group II: cyclophosphamide, a single dose of 200 mg/kg (i.p.) on day 7. Group III: apelin-13 (15 μg/kg), for 7 days (i.p.). Group IV: administered apelin-13 (15 μg/kg) (i.p.) for 7 days and a single dose of cyclophosphamide (200 mg/kg) (i.p.) on day 7, the rats were sacrificed on day 8. Lactate dehydrogenase, cardiac troponin I (cTnI), creatine kinase MB (CK-MB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), malondialdehyde, creatinine, and blood urea nitrogen were found to be high in the cyclophosphamide group; however, these values were reduced with apelin-13 administration. Antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, and reduced glutathione (GSH) decreased in the cyclophosphamide group, and apelin-13 increased these enzyme activities. In addition, histopathological examinations also supported the results obtained. The findings of this study showed that apelin-13 has a protective effect against cardiorenal toxicity caused by cyclophosphamide.
Some Quot schemes in tilted hearts and moduli spaces of stable pairs
Authors: Rota Franco 
Published: October 2021

For a smooth projective variety [Formula: see text], we study analogs of Quot schemes using hearts of non-standard [Formula: see text]-structures of [Formula: see text]. The technical framework uses families of [Formula: see text]-structures as studied in A. Bayer, M. Lahoz, E. Macrì, H. Nuer, A. Perry and P. Stellari, Stability conditions in families, preprint (2019), arXiv:1902.08184. We provide several examples and suggest possible directions of further investigation, as we reinterpret moduli spaces of stable pairs, in the sense of M. Thaddeus, Stable pairs, linear systems and the Verlinde formula, Invent. Math. 117(2) (1994) 317–353; D. Huybrechts and M. Lehn, Stable pairs on curves and surfaces, J. Algebraic Geom. 4(1) (1995) 67–104, as instances of Quot schemes.
An Evaluation of Dose-Related HPV Vaccine Effectiveness Using Central Registries in Michigan
Authors: Gargano Julia W. , You Mei , Potter Rachel , Alverson Georgetta , Swanson Robert , Saraiya Mona , Markowitz Lauri E. , Copeland Glenn 
Published: October 2021

Abstract

Background:
Human papillomavirus (HPV) vaccine effectiveness (VE) evaluations provide important information for vaccination programs. We established a linkage between statewide central registries in Michigan to estimate HPV VE against in situ and invasive cervical lesions (CIN3+).

Methods:
We linked females in Michigan's immunization and cancer registries using birth records to establish a cohort of 773,193 women with known vaccination history, of whom 3,838 were diagnosed with CIN3+. Residential address histories from a stratified random sample were used to establish a subcohort of 1,374 women without CIN3+ and 2,900 with CIN3+ among continuous Michigan residents. VE and 95% confidence intervals (CI) were estimated using cohort and case–cohort methods for up-to-date (UTD) vaccination and incomplete vaccination with 1 and 2 doses, and stratified by age at vaccination.

Results:
Both analytic approaches demonstrated lower CIN3+ risk with UTD and non-UTD vaccination vs. no vaccination. The cohort analysis yielded VE estimates of 66% (95% CI, 60%–71%) for UTD, 33% (95% CI, 18%–46%) for 2 doses-not UTD, and 40% (95% CI, 27%–50%) for 1 dose. The case–cohort analysis yielded VE estimates of 72% (95% CI, 64%–79%) for UTD, 39% (95% CI, 10%–58%) for 2 doses-not UTD, and 48% (95% CI, 25%–63%) for 1 dose. VE was higher for vaccination at age &lt;20 than ≥20 years.

Conclusions:
The statewide registry linkage found significant VE against CIN3+ with incomplete HPV vaccination, and an even higher VE with UTD vaccination.

Impact:
Future VE evaluations by number of doses for women vaccinated at younger ages may further clarify dose-related effectiveness.
Inactivation of AMPK Leads to Attenuation of Antigen Presentation and Immune Evasion in Lung Adenocarcinoma
Authors: Gao Yajing , Päivinen Pekka , Tripathi Sushil , Domènech-Moreno Eva , Wong Iris P.L. , Vaahtomeri Kari , Nagaraj Ashwini S. , Talwelkar Sarang S. , Foretz Marc , Verschuren Emmy W. , Viollet Benoit , Yan Yan , Mäkelä Tomi P. 
Published: October 2021

Abstract

Purpose:
Mutations in STK11 (LKB1) occur in 17% of lung adenocarcinoma (LUAD) and drive a suppressive (cold) tumor immune microenvironment (TIME) and resistance to immunotherapy. The mechanisms underpinning the establishment and maintenance of a cold TIME in LKB1-mutant LUAD remain poorly understood. In this study, we investigated the role of the LKB1 substrate AMPK in immune evasion in human non—small cell lung cancer (NSCLC) and mouse models and explored the mechanisms involved.

Experimental Design:
We addressed the role of AMPK in immune evasion in NSCLC by correlating AMPK phosphorylation and immune-suppressive signatures and by deleting AMPKα1 (Prkaa1) and AMPKα2 (Prkaa2) in a KrasG12D-driven LUAD. Furthermore, we dissected the molecular mechanisms involved in immune evasion by comparing gene-expression signatures, AMPK activity, and immune infiltration in mouse and human LUAD and gain or loss-of-function experiments with LKB1- or AMPK-deficient cell lines.

Results:
Inactivation of both AMPKα1 and AMPKα2 together with Kras activation accelerated tumorigenesis and led to tumors with reduced infiltration of CD8+/CD4+ T cells and gene signatures associated with a suppressive TIME. These signatures recapitulate those in Lkb1-deleted murine LUAD and in LKB1-deficient human NSCLC. Interestingly, a similar signature is noted in human NSCLC with low AMPK activity. In mechanistic studies, we find that compromised LKB1 and AMPK activity leads to attenuated antigen presentation in both LUAD mouse models and human NSCLC.

Conclusions:
The results provide evidence that the immune evasion noted in LKB1-inactivated lung cancer is due to subsequent inactivation of AMPK and attenuation of antigen presentation.
DIRAS3: An Imprinted Tumor Suppressor Gene that Regulates RAS and PI3K-driven Cancer Growth, Motility, Autophagy, and Tumor Dormancy
Authors: Bildik Gamze , Liang Xiaowen , Sutton Margie N. , Bast Robert C. , Lu Zhen 
Published: October 2021

Abstract
DIRAS3 is an imprinted tumor suppressor gene that encodes a 26 kDa GTPase with 60% amino acid homology to RAS, but with a distinctive 34 amino acid N-terminal extension required to block RAS function. DIRAS3 is maternally imprinted and expressed only from the paternal allele in normal cells. Loss of expression can occur in a single “hit” through multiple mechanisms. Downregulation of DIRAS3 occurs in cancers of the ovary, breast, lung, prostate, colon, brain, and thyroid. Reexpression of DIRAS3 inhibits signaling through PI3 kinase/AKT, JAK/STAT, and RAS/MAPK, blocking malignant transformation, inhibiting cancer cell growth and motility, and preventing angiogenesis. DIRAS3 is a unique endogenous RAS inhibitor that binds directly to RAS, disrupting RAS dimers and clusters, and preventing RAS-induced transformation. DIRAS3 is essential for autophagy and triggers this process through multiple mechanisms. Reexpression of DIRAS3 induces dormancy in a nu/nu mouse xenograft model of ovarian cancer, inhibiting cancer cell growth and angiogenesis. DIRAS3-mediated induction of autophagy facilitates the survival of dormant cancer cells in a nutrient-poor environment. DIRAS3 expression in dormant, drug-resistant autophagic cancer cells can serve as a biomarker and as a target for novel therapy to eliminate the residual disease that remains after conventional therapy.
Overcoming Gemcitabine Resistance in Pancreatic Cancer Using the BCL-XL–Specific Degrader DT2216
Authors: Thummuri Dinesh , Khan Sajid , Underwood Patrick W. , Zhang Peiyi , Wiegand Janet , Zhang Xuan , Budamagunta Vivekananda , Sobh Amin , Tagmount Abderrahmane , Loguinov Alexander , Riner Andrea N. , Akki Ashwin S. , Williamson Elizabeth , Hromas Robert , Vulpe Christopher D. , Zheng Guangrong , Trevino Jose G. , Zhou Daohong 
Published: October 2021

Abstract
Pancreatic cancer is the third most common cause of cancer-related deaths in the United States. Although gemcitabine is the standard of care for most patients with pancreatic cancer, its efficacy is limited by the development of resistance. This resistance may be attributable to the evasion of apoptosis caused by the overexpression of BCL-2 family antiapoptotic proteins. In this study, we investigated the role of BCL-XL in gemcitabine resistance to identify a combination therapy to more effectively treat pancreatic cancer. We used CRISPR-Cas9 screening to identify the key genes involved in gemcitabine resistance in pancreatic cancer. Pancreatic cancer cell dependencies on different BCL-2 family proteins and the efficacy of the combination of gemcitabine and DT2216 (a BCL-XL proteolysis targeting chimera or PROTAC) were determined by MTS, Annexin-V/PI, colony formation, and 3D tumor spheroid assays. The therapeutic efficacy of the combination was investigated in several patient-derived xenograft (PDX) mouse models of pancreatic cancer. We identified BCL-XL as a key mediator of gemcitabine resistance. The combination of gemcitabine and DT2216 synergistically induced cell death in multiple pancreatic cancer cell lines in vitro. In vivo, the combination significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice compared with the individual agents in pancreatic cancer PDX models. Their synergistic antitumor activity is attributable to DT2216-induced degradation of BCL-XL and concomitant suppression of MCL-1 by gemcitabine. Our results suggest that DT2216-mediated BCL-XL degradation augments the antitumor activity of gemcitabine and their combination could be more effective for pancreatic cancer treatment.
Stability of maternal serum free β-hCG following whole blood sample transit: First trimester Down’s syndrome screening in Scotland
Authors: Ballantyne Angela , Rashid Lorna , Pattenden Rebecca 
Published: October 2021

Background Maternal serum free beta human chorionic gonadotrophin (free β-hCG) is used as a biomarker in first trimester screening for fetal Down’s syndrome. Production of free β-hCG can occur in vitro in a time- and temperature-dependent manner; thus, the current Scottish screening protocol states samples must be received by the laboratory within 72 h. To assess the validity of the protocol, an audit was conducted to determine the impact of transit time on maternal serum free β-hCG multiple of median (MoM) values in the Scottish screened population. Methods Corrected MoM values from antenatal screening carried out over one year (April 2017 to March 2018) were stratified according to sample transit time and compared. To investigate possible environmental temperature effects, the data were split according to season and maternal serum free β-hCG concentrations from summer and winter compared. Results Of the 28,368 samples included in the study, 24,368 were received on the day of phlebotomy or after one day in transit. Only 1.5% of samples were received after 3 days in transit. The difference in maternal serum free β-hCG MoM values due to transit time was not significant. No statistical difference was found between maternal serum free β-hCG concentrations from samples collected in summer and winter months. Conclusion The current sample receipt protocol in use by the Scottish Down’s syndrome screening programme is fit for purpose.
Effects of silane coupling agent modifications of hollow glass microspheres on syntactic foams with epoxy matrix
Authors: Li Rui , Fan Guisen , Wang Peng , Ouyang Xiao , Ma Ning , Wei Hao 
Published: October 2021

A syntactic foam was prepared from an epoxy resin matrix and modified hollow glass microsphere fillers. Modification by silane coupling agents with different molecular structures was analyzed, and the optimal content of the silane coupling agent was determined. The results demonstrated that all silane coupling agents enhanced the adhesion between the hollow glass microspheres and epoxy resin matrix, resulting in enhanced water absorption, compressive performance, tensile performance, and bending performance compared to those prepared using unmodified hollow glass microspheres. Among silane coupling agents with different end groups, the one with a sulfhydryl end group exhibited optimal modification for hollow glass microspheres. Among the silane coupling agents with different backbone structures, the one with silanol groups exhibited the optimal modification of hollow glass microspheres. Additionally, the performance of the syntactic foams was optimal when 6% of the silanol-containing coupling agent was used. The results demonstrated that syntactic foams prepared with hollow glass microspheres modified by silane coupling agents exhibited improvements in water absorption, compressive performance, tensile performance, and bending performance, compared with those prepared using unmodified hollow glass microspheres. Among silane coupling agents with different end structures, the one with a sulfhydryl group as end group showed the best modification effect on hollow glass microspheres. The water absorption was 0.35%, the compressive strength was 62.15 MPa, the tensile strength was 40.15 MPa, and the bending strength was 53.17 MPa. Among silane coupling agents with different backbone structures, the one with silanol groupsbonds showed the best results. Its compressive strength was up to 64.15 MPa, the tensile strength was 35.47 MPa, and the bending strength was 53.99 MPa.
Treatment Outcome in Bilateral Cleft lip and Palate Patients Evaluated With the Huddart-Bodenham Scoring System and the Bilateral Cleft lip and Palate Yardstick: A Systematic Review
Authors: Kuang Wenying , Aarts Miranda , Kuijpers-Jagtman Anne Marie , He Hong , Ongkosuwito Edwin M. 
Published: October 2021

Objectives To assess treatment outcome (transversal and sagittal dental arch relationships) and its determinants in complete bilateral cleft lip and palate (BCLP) evaluated with the modified Huddart-Bodenham scoring system and the BCLP Yardstick. Materials and methods Multiple electronic databases were searched without time limitation. Randomized clinical trials, cohort and case control studies using BCLP Yardstick and/or modified Huddart-Bodenham system to judge treatment outcome of patients with BCLP were included. The Risk of Bias in Nonrandomized Studies of Interventions tool and Grading of Recommendations, Assessment, Development, and Evaluation was used. Results Of the 528 studies identified by the electronic search, only eight retrospective studies met the inclusion criteria and were included. A total of 12 cleft centers were represented. All treatment protocols differed and background information was underreported. The results for the BCLP yardstick showed that all except the centers in New Zealand had a mean score lower than 3, indicating good treatment results. However, these studies had a moderate to high risk of bias. The modified Huddart-Bodenham scores were negative in all studies. No further meta-analysis was done due to heterogeneity and high risk of bias. The quality of evidence was graded as very low. Conclusion Results for the dental arch relationship of studies in complete BCLP and possible determinants were not synthesized due to very low quality of evidence. Clinical research for patients with BCLP should focus on sound methodological designs to enable evidence-based decision making to improve treatment for patients with BCLP and thereby hopefully their quality of life.
Aplastic anemia secondary to tyrosine kinase inhibitor therapy in a patient with chronic myeloid leukemia
Authors: Kassar Olfa , Mallek Rahma , Ben Said Fatma , Kallel Faten , Ksouda Kamilia , Khabir Abdelmajid , Elloumi Moez 
Published: October 2021

Introduction Nilotinib, as the second generation of tyrosine kinase inhibitor, has significant efficacy in patients with chronic myeloid leukemia resistant or intolerant to Imatinib. Aplastic anemia induced by tyrosine kinase inhibitors is an uncommon complication. Case report A 34-year-old female case with CML in the chronic phase was treated with Imatinib in first-line therapy. Nilotinib was switched because of failure to achieve complete cytogenetic response at 6 months following Imatinib. Three years with Nilotinib, the patient developed a persistent pancytopenia grade 4 while a major molecular response was achieved. Management & Outcome Nilotinib was discontinued. However, the hematologic finding of the patient had not recovered after three months. A bone marrow biopsy showed marked hypocellularity and fatty tissue without evidence of myelofibrosis. Immunosuppressive therapy was started. Unfortunately, the patient died due to septic and hemorrhagic shock nine months after Nilotinib interruption. According to Naranjo's algorithm, the causality relationship with the drug is probable with a score of 5. Discussion Aplastic anemia is an uncommon adverse event of tyrosine kinase inhibitors but it can be a fatal complication. The early diagnosis of aplastic anemia related to Nilotinib therapy is needed to avoid further detrimental effects of the drug.
Success of placement and complications during v-gel placement and maintenance of anaesthesia
Authors: Hecker-Turkovic Kathrin , Hartmann Katrin , Dörfelt René 
Published: October 2021

Objectives Airway management during anaesthesia in cats is always a demanding task and is associated with several complications. The aim of this study was to evaluate the practicability and complications during feline-specific laryngeal mask placement in anaesthetised cats as an alternative to endotracheal intubation. Methods In this prospective clinical study, laryngeal masks were placed in 148 anaesthetised cats. Success of placement was evaluated by capnography. Results Placement was possible at the first attempt in 136 cats, at the second attempt in eight cats and at the third attempt in one cat. In one cat, placement was not possible. Two cats were excluded. Failure to position the laryngeal mask at the first attempt was not different between laryngeal mask sizes ( P = 0.313) or positioning during placement ( P = 0.406). In nine cats, the laryngeal mask dislocated during the procedure. Dislocation occurred more often in the dorsal position than in the sternal ( P = 0.018) and right lateral positions ( P = 0.046). Mucous obstruction of the laryngeal mask occurred in one of these cats and regurgitation in another. Material-related issues, such as disconnection of the parts of the laryngeal mask and leakage of the balloon, were observed in 2/8 laryngeal masks. Conclusions and relevance The placement of a feline-specific laryngeal mask was easy to perform. In about 7% of the cases, replacement of the device was required due to mispositioning or dislocation. Full monitoring, including capnography, should be provided to uncover dislocation and airway obstruction immediately.