bluuebunny/crossref_metadata_2025_split huggingface dataset:
O‐glycosylated clusterin as a sensitive marker for diagnosing early stages of prostate cancer
Authors: Kazuno Saiko , Fujimura Tsutomu , Fujime Makoto , Miura Yoshiki , Ueno Takashi 
Published: December 2020

AbstractBackgroundProstate‐specific antigen (PSA) has been the most popular diagnostic marker for prostate cancer. The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations. The aim of this study was to develop a better resolution for diagnosing prostate cancer to overcome the disadvantage of PSA.MethodsWe focused on the glycosylation status of patients' serum proteins and conducted comprehensive lectin microarray analyses to characterize N‐ and O‐glycans using sera from prostate cancer and benign prostatic diseases. Next, we retrieved candidate serum proteins with characteristic glycan structures using lectin‐immobilized beads and identified them by quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling. Finally, we constructed a new assay to quantify a candidate glycoprotein with the newly identified glycans.ResultsLectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O‐glycosylated proteins are more abundant in sera from patients with prostate cancer. Then, serum glycoproteins preferentially adsorbed onto Jacalin‐Agarose as well as biotin‐ACA/and biotin‐MPA/streptavidin‐immobilized magnetic beads were isolated, labeled with iTRAQ, and identified using quantitative mass spectrometry. It was found that the ACA‐ and MPA‐recognizable clusterin was more enriched in patients' sera from prostate cancer compared with those from benign prostatic diseases. Following this discovery, we constructed a Luminex‐based assay to quantify O‐glycosylated clusterin, in which total serum clusterin was first captured on anti‐clusterin antibody‐immobilized beads, and then clusterin‐associated O‐glycans were determined by the pair of biotin‐MPA and streptavidin‐phycoerythrin. When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA‐recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease.ConclusionFor PSA values that measure less than 10 ng/ml, the serum O‐glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
Treatment goals and changes over time in older patients with non-curable cancer
Authors: Stegmann M. E. , Brandenbarg D. , Reyners A. K. L. , van Geffen W. H. , Hiltermann T. J. N. , Berendsen A. J. 
Published: December 2020

Abstract
Purpose
To investigate the treatment goals of older patients with non-curable cancer, whether those goals changed over time, and if so, what triggered those changes.

Methods
We performed a descriptive and qualitative analysis using the Outcome Prioritization Tool (OPT) to assess patient goals across four conversations with general practitioners (GPs) over 6 months. Text entries from electronic patient records (hospital and general practice) were then analyzed qualitatively for this period.

Results
Of the 29 included patients, 10 (34%) rated extending life and 9 (31%) rated maintaining independence as their most important goals. Patients in the last year before death (late phase) prioritized extending life less often (3 patients; 21%) than those in the early phase (7 patients; 47%). Goals changed for 16 patients during follow-up (12 in the late phase). Qualitative analysis revealed three themes that explained the baseline OPT scores (prioritizing a specific goal, rating a goal as unimportant, and treatment choices related to goals). Another three themes related to changes in OPT scores (symptoms, disease course, and life events) and stability of OPT scores (stable situation, disease-unrelated motivation, and stability despite symptoms).

Conclusion
Patients most often prioritized extending life as the most important goal. However, priorities differed in the late phase of the disease, leading to changed goals. Triggers for change related to both the disease (e.g., symptoms and course) and to other life events. We therefore recommend that goals should be discussed repeatedly, especially near the end of life.

Trial registration
OPTion study: NTR5419
Ovarian Vein Thrombosis: A Narrative Review
Authors: Riva Nicoletta , Calleja-Agius Jean 
Published: December 2020

AbstractOvarian vein thrombosis (OVT) is a rare type of venous thromboembolism. The most common risk factors for OVT include pregnancy, oral contraceptives, malignancies, recent surgery, and pelvic infections; however, in 4 to 16% of cases, it can be classified as idiopathic. Most of the available information regards pregnancy-related OVT, which has been reported to complicate 0.01 to 0.18% of pregnancies and to peak around 2 to 6 days after delivery or miscarriage/abortion. The right ovarian vein is more frequently involved (70–80% of cases). Clinical features of OVT include abdominal pain and tenderness, fever, and gastrointestinal symptoms. The most typical finding is the presence of a palpable abdominal mass, although reported in only 46% of cases. OVT can be the cause of puerperal fever in approximately a third of women. Ultrasound Doppler is the first-line imaging, because of its safety, low cost, and wide availability. However, the ovarian veins are difficult to visualize in the presence of bowel meteorism or obesity. Thus, computed tomography or magnetic resonance imaging is often required to confirm the presence and extension of the thrombosis. In oncological patients, OVT is often an incidental finding at abdominal imaging. Mortality related to OVT is nowadays low due to the combination treatment of parenteral broad-spectrum antibiotics (until at least 48 hours after fever resolution) and anticoagulation (low-molecular-weight heparin, vitamin K antagonists, or direct oral anticoagulants). Anticoagulant treatment duration of 3 to 6 months has been recommended for postpartum OVT, while no anticoagulation has been suggested for incidentally detected cancer-associated OVT.
Building Blocks of Laser Safety
Authors: Barat Ken 
Published: December 2020

The goal of this part of the book is to review items that are considered the core of laser safety and laser user awareness. Some items, like explanation of control measures and non-beam hazards and eyewear selection, will be discussed in later chapters. By being aware of the biological hazards, the laser user will be more educated and careful. This has not always been the practice, but we all keep trying.
Laser hazard classification dictates control measures and product safety controls. Biological effects/properties of laser wavelengths explain the damage concerns. The unique properties of lasers would fit on this list, but here, listing them seems unnecessary.
Then come items that put these concerns in play: the role of the laser safety officer or adviser; standards and regulations, the real reasons why some even bother about laser safety; and the responsibility of users, who are, as always, the first and final critical factor.
Just like humans contain DNA as our fundamental building blocks, laser safety has a few fundamental elements of its own. No text on laser safety can avoid covering them.
Occurrence of XoxF-type methanol dehydrogenases in bacteria inhabiting light lanthanide-rich shale rock
Authors: Roszczenko-Jasińska Paula , Krucoń Tomasz , Stasiuk Robert , Matlakowska Renata 
Published: December 2020

ABSTRACT
This study analyzed the occurrence of lanthanide-dependent (XoxF type) methanol dehydrogenases in the bacterial community dominated by Proteobacteria inhabiting shale rock. In total, 22 sequence matches of XoxF were identified in the metaproteome of the community. This enzyme was produced by bacteria represented by orders such as Rhizobiales, Rhodobacterales, Rhodospiralles, Burkholderiales and Nitrosomonadales. Among the identified XoxF proteins, seven belonged to XoxF1 clade and 15 to XoxF5 clade. This study is the first to show the occurrence of XoxF proteins in the metaproteome of environmental lithobiontic bacterial community colonizing an underground rock rich in light lanthanides. The presented results broaden our understanding of the ecology of XoxF producing bacteria as well as the distribution and diversity of these enzymes in the natural environment.
‘Over-researched’ and ‘Under-researched’ refugee groups: Exploring the phenomena, causes and consequences
Authors: Omata Naohiko 
Published: December 2020

Summary:Drawing upon my fieldwork experience in East Africa, this article sheds light on emerging phenomena of ‘over-researched’ and ‘under-researched’ refugee populations. Over the past years, I have increasingly encountered ‘research fatigue’ amongst certain groups of refugees who have undergone frequent studies by numerous researchers. On the other hand, I have also noticed disappointment and frustration from groups of refugees who feel that they remain ‘under-studied’ despite their hidden challenges and vulnerabilities. While the phenomena of over- and under-research are not new, few studies are done to compare the under- and over-studied refugees and to investigate the causes and consequences of the polarisation of research interest amongst refugee populations. This article thus aims to narrow these gaps and also explores these phenomena in relation to accountability and ethics related to forced migration scholarship. I also present practical actions toward improvement of this research polarisation.
Inhibitors of TGFβR1/ALK4/JNK3/Flt1 Kinases in Cynomolgus Macaques Lead to the Rapid Induction of Renal Epithelial Tumors
Authors: Carreira Vinicius , Standeven Andrew M , Ma Jing Ying , Hardisty Jerry , Cohen Samuel M , Kerns Williams D , Snook Sandra 
Published: December 2020

Abstract
Two young cynomolgus macaques (Macaca fascicularis) given a small molecule kinase inhibitor ((S)-4-((2–(5-chloro-2-fluorophenyl)-5-isopropylpyrimidin-4-yl)amino)-N-(2-hydroxypropyl)nicotinamide [SCIO-120]) via nasogastric intubation gavage, once-daily for 21 days at 400 mg/kg/day, developed an unusual epithelial proliferative process in the renal parenchyma. Morphological and immunohistochemical characterization of the lesions confirmed an invasive malignant epithelial neoplasm (carcinoma). A similar renal neoplasm was seen in a third macaque after a 14-day exposure to a second kinase inhibitor in the same chemical series ((S) 4-((2–(5-chloro-2-fluorophenyl)-5-methoxypyrimidin-4-yl)amino)-N-cyclopropylnicotinamide [SCIO-974]). Despite remarkably short latency periods, exposure to these kinase inhibitors was likely causally associated with the induction of the renal tumors, as renal carcinomas are exceedingly rare spontaneously in macaques. Both SCIO-120 and SCIO-974 were designed as potent TGFβR1 inhibitors (IC50s 37 and 39 nM, respectively). SCIO-120 and SCIO-974 inhibited additional kinases, most notably closely related ALK4 (IC50 = 34  and 20 nM, respectively), c-Jun n-Terminal kinase 3 (JNK3, IC50 = 10 and 20 nM, respectively), and Fms-related tyrosine kinase 1 (29  and 76 nM, respectively). TGFβR1 has been specifically implicated in epithelial proliferative disorders, including neoplasia. Neither SCIO-120 nor SCIO-974 was genotoxic based on bacterial reverse mutation and/or clastogenicity screening assays. The rapid appearance of renal carcinomas in primates following short-term treatment with nongenotoxic kinase inhibitors is remarkable and suggests that the compounds had noteworthy tumor-enhancing effects, hypothetically linked to their TGFβR1 inhibition activity. These observations have implications for mechanisms of carcinogenesis and TGFβR1 biology.
Cool OtOprotective Ear Lumen (COOL) Therapy for Cisplatin-induced Hearing Loss
Authors: Stanford James K. , Morgan Drew S. , Bosworth Nicholas A. , Proctor Georgio , Chen Tianwen , Palmer Trace T. , Thapa Punam , Walters Bradley J. , Vetter Douglas E. , Black Robert D. , Rogers Lesco L. , Spankovich Christopher 
Published: December 2020

Hypothesis:
Localized cooling of the external ear has a protective effect on the susceptibility to cisplatin-induced hearing loss.

Background:
We previously demonstrated significant protection from cisplatin-induced hearing loss using cool water ear canal irrigation. However, the study was limited to a single bolus injection of cisplatin and an acute time period. Here, we examined the application of localized cooling of the ear canal with repeated doses of cisplatin, over an expanded period of time, and using two methods of cooling.

Methods:
Twenty-four guinea pigs (12 male and 12 female) underwent auditory physiological testing (auditory brainstem response and distortion product otoacoustic emissions at 8–32 kHz) and pre/postadministration of cisplatin. Cisplatin (4 mg/kg i.p.) was administered in 3 weekly single injections for a total of 12 mg/kg. While anesthetized, the left ears of the guinea pigs were exposed to either cool water (22°C; ICS Water Caloric Irrigator), a cool ear bar (15°C, cooled by a Peltier device; TNM, Scion NeuroStim), or left uncooled as a sham control. The animals were tested 3 days post each dosage and 1 month post the final dose. At the end of the experiment the animals were euthanized for histological evaluation.

Results:
We found that hearing loss was significantly reduced, and hair cell survival greatly improved, in animals that received cooling treatments compared to cisplatin-only control animals. No significant difference was observed between the two methods of cooling.

Conclusion:
Localized cooling of the ear canal during administration of cisplatin mitigated loss of auditory function and loss of hair cells.
Cochlear Implantation in the Active Duty Military Population: A Survey Assessing Military Readiness and Satisfaction
Authors: Sommerfeldt John M. , Fischer Jakob L. , Morrison Danielle A. , Pillion Elicia , Bernstein Joshua , Tolisano Anthony M. 
Published: December 2020

Objective:
Evaluate the impact of cochlear implantation (CI) on retention for United States active duty (AD) service members.

Study Design:
Retrospective observational study.

Setting:
Tertiary military CI centers.

Patients:
AD service members who underwent CI and completed a telephonic survey.

Main Outcome Measures:
The ability for military personnel to maintain AD status following CI as determined by the nonvolitional hearing-related AD separation rate and whether subjects would recommend CI to other qualified candidates.

Results:
Twenty AD service members who underwent CI between 2004 and 2020 completed a telephonic survey. Fifteen (75%) were single-sided deafness (SSD) and five were traditional CI candidates. The mean age was 40.3 years (range 27.5–64.3), 19 (95%) were male, and 12 (80%) were Caucasian. Ten (50%) were officers and 14 (70%) were noncombat support personnel. Idiopathic sudden sensorineural hearing loss was the most common cause of hearing loss (8, 40%) followed by occupational noise exposure (4, 20%). Sixteen (80%) maintained AD status yielding 46.15 person-years of AD service following CI. For SSD, 14 (93%) maintained AD status yielding 40.54 person-years of AD service. The nonvolitional hearing-related patient separation rate for CI recipients with bilateral hearing loss was 35.65 cases per 100 AD person-years and 0 cases per 100 person-years for SSD candidates. Nineteen (95%) stated they would recommend CI to other AD CI candidates.

Conclusions:
The vast majority of AD CI recipients, and particularly those with SSD, are able to remain on AD after surgery and report a high degree of satisfaction with their implant.
Inferior Vena Cava Tumor Thrombus From Thyroid Cancer Detected by 68Ga-PSMA-617 PET/CT
Authors: Li Hui , Liu Yanqing , Zang Jie , Yang Zhi , Lin Yansong 
Published: December 2020

Abstract
A 61-year-old woman was diagnosed with progressive metastatic radioactive iodine refractory differentiated thyroid cancer and underwent multitargeted tyrosine kinase inhibitor (TKI) Donafenib therapy. After 12 months of therapy, she developed resistance to TKI. Considering the limited treatment options available, a 68Ga–prostate-specific membrane antigen (PSMA)–617 PET/CT was conducted for potential therapeutic target. 68Ga-PSMA-617 PET/CT showed an intense radiotracer uptake in inferior vena cava, which was subsequently confirmed as tumor thrombus. Thus, this patient is a rare case in which the tumor thrombus from thyroid cancer was discovered in inferior vena cava via 68Ga-PSMA-617 PET/CT.
Toll-Like Receptors, Associated Biochemical Signaling Networks, and S100 Ligands
Authors: Gupta Sahil , Tsoporis James N. , Jia Song-Hui , dos Santos Claudia C. , Parker Thomas G. , Marshall John C. 
Published: December 2020

ABSTRACT
Host cells recognize molecules that signal danger using pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are the most studied class of PRRs and detect pathogen-associated molecular patterns and danger-associated molecular patterns. Cellular TLR activation and signal transduction can therefore contain, combat, and clear danger by enabling appropriate gene transcription. Here, we review the expression, regulation, and function of different TLRs, with an emphasis on TLR-4, and how TLR adaptor protein binding directs intracellular signaling resulting in activation or termination of an innate immune response. Finally, we highlight the recent progress of research on the involvement of S100 proteins as ligands for TLR-4 in inflammatory disease.
Internal medicine clerkship amidst COVID-19 pandemic: clinical learning experience of undergraduate medical students at Makerere University, Uganda: a cross-sectional study
Authors: Bongomin Felix , Olum Ronald , Nakiyingi Lydia , Rejani Lalitha , Ssinabulya Isaac , Sekaggya-Wiltshire Christine , Ocama Ponsiano , Byakika-Kibwika Pauline 
Published: December 2020

ABSTRACTBackgroundThe coronavirus-2019 (COVID-19) pandemic continues to impose a significant impact on medical education. We aimed to describe the clinical learning experience of undergraduate medical students undertaking internal medicine clerkship during the COVID-19 pandemic at Makerere University, Uganda.MethodsA descriptive, cross-sectional study among medical students in clinical years of study pursuing the Bachelor of Medicine and Bachelor of Surgery undergraduate degree program was conducted in November 2020. Only 3rd (junior clerks) and 5th (senior clerks) year medical students whose internal medicine clerkships were interrupted by the COVID-19 pandemic were studied.ResultsData of 188 (95%) eligible clinical year students; junior (101, 54.0%) and senior (86, 46.0%) were analysed. Median age was 24 (range: 22-42) years. Majority (70.1%) were male and Ugandan nationals (94.1%). Sixty-four (30.3%) students reported inadequate personal protective equipment, 152 (81.7%) felt at risk of contracting COVID-19, and 127 (67.9%) said it was difficult to observe COVID-19 standard operating procedures. Twenty-two students (11.9%) were discouraged from pursuing a career in internal medicine. Overall, most students reported good or excellent clinical experience pre-COVID-19 era compared to during the COVID-19 era (4.0 vs. 3.5, p<0.0001). Senior clerks significantly believed that the time allocated for the rotation was adequate (p<0.0001) and they were able to complete their study objectives (p<0.001), compared to the junior clerks. Senior clerks believed that learning was difficult when combined with junior clerks (p=0.013). About half of the students (51.4%, n=95) reported clinical teaching should remain as it was in the pre-COVID-19 era.ConclusionsThe COVID-19 pandemic has had a significantly negative effect on the clinical learning experience of the students. There is need to review the current teaching and learning methods to suit teaching and learning during pandemics of highly infectious diseases to ensure safe and effective learning experience.HighlightsNearly half of the medical students reported a negative clinical learning experience during their internal medicine clerkship in the COVID-19 pandemic.Over two-thirds of the participants expressed that it was difficult to observe COVID-19 prevention standard operating procedures during their clinical rotations.Over 80% of the medical students felt at risk of contracting COVID-19 during their clinical rotation.About one-third of the medical students reported inadequacy in personal protective equipment like masks during their rotation.
Immediate early gene expression dynamics in vivo segregates neuronal ensemble of multiple memories
Authors: Meenakshi P. , Kumar S. , Balaji J. 
Published: December 2020

AbstractImmediate early genes (IEGs) are widely used as a marker for neuronal plasticity. Here, we model the dynamics of IEG expression as a consecutive, irreversible first order reaction with a limiting substrate. We show that such a model, together with two-photon in vivo imaging of IEG expression, can be used to identify distinct neuronal subsets representing multiple memories. We image retrosplenial cortex (RSc) of cFOS-GFP transgenic mice to follow the dynamics of cellular changes resulting from both seizure and contextual fear conditioning behaviour. The analytical expression allowed us to segregate the neurons based on their temporal response to one specific behavioural event, thereby improving the sensitivity of detecting plasticity related neurons. This enables us to establish representation of context in RSc at the cellular scale following memory acquisition. Thus, we obtain a general method which distinguishes neurons that took part in multiple temporally separated events, by measuring fluorescence from individual neurons in live mice.SummaryIdentifying neuronal ensemble associated with different memories is vital in modern neuroscience. Meenakshi et al model and use the temporal expression dynamics of IEGs rather than thresholded intensities of the probes to identify the neurons encoding different memory in vivo.Graphical abstract
Recovery of neural dynamics criticality in personalized whole brain models of stroke
Authors: Rocha Rodrigo P. , Koçillari Loren , Suweis Samir , De Grazia Michele De Filippo , de Schotten Michel Thiebaut , Zorzi Marco , Corbetta Maurizio 
Published: December 2020

ABSTRACTThe critical brain hypothesis states that biological neuronal networks, because of their structural and functional architecture, work near phase transitions for optimal response to internal and external inputs. Criticality thus provides optimal function and behavioral capabilities. We test this hypothesis by examining the influence of brain injury (strokes) on the criticality of neural dynamics estimated at the level of single participants using directly measured individual structural connectomes and whole-brain models. Lesions engender a sub-critical state that recovers over time in parallel with behavior. The improvement of criticality is associated with the re-modeling of specific white matter connections. We show that personalized whole-brain dynamical models poised at criticality track neural dynamics, alteration post-stroke, and behavior at the level of single participants.