bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal patterns in greenhouse gas emissions from thermokarst lakes in Central Yakutia (Eastern Siberia)
Authors: Hughes‐Allen Lara , Bouchard Frédéric , Laurion Isabelle , Séjourné Antoine , Marlin Christelle , Hatté Christine , Costard François , Fedorov Alexander , Desyatkin Alexey
Published: December 2020

In the ice‐rich permafrost area of Central Yakutia (Eastern Siberia, Russia), climate warming and other natural and anthropogenic disturbances have caused permafrost degradation and soil subsidence, resulting in the formation of numerous thermokarst (thaw) lakes. These lakes are hotspots of greenhouse gas emissions, but with substantial spatial and temporal heterogeneity across the Arctic. We measured dissolved CO2 and CH4 concentrations in thermokarst lakes of Central Yakutia and their seasonal patterns over a yearly cycle. Lakes formed over the Holocene (alas lakes) are compared to lakes that developed over the last decades. The results show striking differences in dissolved greenhouse gases (up to two orders of magnitude) between lake types and seasons. Shallow lakes located in hydrologically closed alas depressions acted as CO2 sinks and strong sources of diffusive CH4 during some seasons (ebullition was not assessed). Recent thermokarst lakes were moderate to extremely high sources of diffusive CO2 and CH4, with considerable accumulation of greenhouse gas under the ice cover (winter) or in the deepest water layers (summer), highlighting the need to include spring and autumn as critical periods for integrated assessments. The water column was stratified in winter (all lake types) and especially in summer (recent thermokarst lakes), generating anoxia in bottom waters and favoring CH4 production and storage, particularly in the most organic‐rich lakes. The diffusive fluxes measured from thermokarst lakes of this typical taiga alas landscape of Central Yakutia are among the highest presented across Arctic and subarctic regions.
Industrialization of hybrid Si/III–V and translucent planar micro‐tracking modules
Authors: Nardin Gaël , Domínguez César , Aguilar Álvaro Fernando , Anglade Laetitia , Duchemin Mathilde , Schuppisser David , Gerlich Florian , Ackermann Mathieu , Coulot Laurent , Cuénod Blaise , Petri Delphine , Niquille Xavier , Badel Nicolas , Lachowicz Agata , Despeisse Matthieu , Levrat Jacques , Ballif Christophe , Askins Stephen , Núñez Rubén , Jost Norman , Vallerotto Guido , Antón Ignacio
Published: December 2020

A tracking‐integrated hybrid micro‐concentrator module is presented that can harvest direct, diffuse, and albedo irradiance components. It uses biconvex 180× lens arrays to concentrate direct light on high‐efficiency III–V solar cells (29% module efficiency has been demonstrated outdoors on direct sunlight at Concentrator Standard Test Conditions) and a planar micro‐tracking mechanism to allow installation in static frames. Two architectures have been developed to harvest diffuse irradiance: (1) a hybrid architecture where the backplane is covered with monofacial or bifacial Si cells; (2) a translucent architecture where diffuse light is transmitted through the module for dual‐land‐use applications, such as agrivoltaics. Simulations show that the hybrid architecture provides an excess of yearly energy production compared to 20% efficiency flat‐plate photovoltaic (PV) module in all locations studied, including those with a low direct normal irradiance (DNI) content, and up to 38% advantage in high‐DNI locations. The use of bifacial heterojunction and interdigitated back‐contact Si cells has been explored for the glass–Si–glass backplane laminate to harvest albedo light. Bifacial gains modeled can boost energy yield by about 30% in the best scenario. We discuss the perspectives of the translucent modules for dual‐land‐use applications as well, such as integration in greenhouses for agriculture‐integrated PV (agrivoltaics). This architecture can provide up to 47% excess electricity compared to a spaced reference Si array that transmits the same amount of solar photosynthetically active radiation for crop production. The HIPERION consortium funded by the European H2020 program is making an intensive effort to take this technology to the industrial scale.
Retention and job satisfaction of school psychologists
Authors: Young Ellie L. , Moulton Sara E. , Julian Alexander , Smith Alivia , Butler Rachel
Published: December 2020

Retention of current school psychologists is a vital strategy for addressing shortages in the field. Understanding what contributes to why school psychologists stay in the field has the potential to influence leaders and administrators to ensure that they are targeting what matters most to school psychologists. Survey results from 134 school psychologists indicated that they stay in the field because they enjoy working with children and believe their work makes a difference. These generally satisfied school psychologists also shared that they work with teams that facilitate effective and creative problem solving and were acknowledged for their contributions. For the few school psychologists who expressed dissatisfaction, their responses communicated a lack of professional self‐efficacy: their opinions were not valued, they did not believe they were effective in their roles, administrators did not value their contributions, and they did not believe they could make a difference for students. Implications for practice highlight the need for district and building administrators to ensure that school psychologists have manageable caseloads that allow them to work directly with children and to be a part of teams that solve problems.
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

Background

Prostate‐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.

Methods

We 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.

Results

Lectin 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.

Conclusion

For 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

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
Modelling of variable‐speed refrigeration for fast‐frequency control in low‐inertia systems
Authors: Vorwerk Johanna , Markovic Uros , Aristidou Petros , Vrettos Evangelos , Hug Gabriela
Published: December 2020

In modern power systems, shiftable loads contribute to the flexibility needed to increase robustness and ensure security. Thermal loads are among the most promising candidates for providing such service due to the large thermal storage time constants. This study demonstrates the use of variable‐speed refrigeration (VSR) technology, based on brushless DC motors, for the fast‐frequency response. First, the authors derive a detailed dynamic model of a single‐phase VSR unit suitable for time‐domain and small‐signal stability analysis in low‐inertia systems. For analysing dynamic interactions with the grid, they consider the aggregated response of multiple devices. However, the high computational cost involved in analysing large‐scale systems leads to the need for reduced‐order models. Thus, a set of reduced‐order models is derived through transfer function fitting of data obtained from time‐domain simulations of the detailed model. The modelling requirements and the accuracy versus computational complexity trade‐off are discussed. Finally, the time‐domain performance and frequency‐domain analyses reveal substantial equivalence between the full‐ and suitable reduced‐order models, allowing the application of simplified models in large‐scale system studies.
Ovarian Vein Thrombosis: A Narrative Review
Authors: Riva Nicoletta , Calleja-Agius Jean
Published: December 2020

Ovarian 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

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

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

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

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

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

Background

The 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.

Methods

A 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.

Results

Data 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.

Conclusions

The 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.

Highlights

Nearly 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

Immediate 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.

Identifying 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

The 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.
Kinetics of antibody responses dictate COVID-19 outcome
Authors: Lucas Carolina , Klein Jon , Sundaram Maria , Liu Feimei , Wong Patrick , Silva Julio , Mao Tianyang , Oh Ji Eun , Tokuyama Maria , Lu Peiwen , Venkataraman Arvind , Park Annsea , Israelow Benjamin , Wyllie Anne L. , Vogels Chantal B. F. , Muenker M. Catherine , Casanovas-Massana Arnau , Schulz Wade L. , Zell Joseph , Campbell Melissa , Fournier John B. ,   Yale IMPACT Research Team, Grubaugh Nathan D. , Farhadian Shelli , Wisnewski Adam V. , Cruz Charles Dela , Omer Saad , Ko Albert I. , Ring Aaron , Iwasaki Akiko
Published: December 2020

Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). Yet, the exact feature of antibody responses that governs COVID-19 disease outcomes remain unclear. Here, we analysed humoral immune responses in 209 asymptomatic, mild, moderate and severe COVID-19 patients over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-Spike (S) IgG levels, length of hospitalization and clinical parameters associated with worse clinical progression. While high anti-S IgG levels correlated with worse disease severity, such correlation was time-dependent. Deceased patients did not have higher overall humoral response than live discharged patients. However, they mounted a robust, yet delayed response, measured by anti-S, anti-RBD IgG, and neutralizing antibody (NAb) levels, compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, while sera from 89% of patients displayed some neutralization capacity during their disease course, NAb generation prior to 14 days of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levelsper se, but rather with the delayed kinetics of NAb production.
Further development of spinal cord retreatment dose estimation: including radiotherapy with protons and light ions
Authors: Moore Joshua W. , Woolley Thomas E. , Hopewell John W. , Jones Bleddyn
Published: December 2020

A new graphical user interface (GUI) was developed to aid in the assessment of changes in the radiation tolerance of spinal cord/similar central nervous system tissues with time between two treatment courses. The GUI allows any combination of photons, protons (or ions) to be used as the initial, or retreatment, course. Allowances for clinical circumstances, of reduced tolerance, can also be made. The radiobiological model was published previously and has been incorporated with additional checks and safety features, to be as conservative as possible. The proton option includes use of a fixed RBE of 1.1 (set as the default), or a variable RBE, the latter depending on the proton linear energy transfer (LET) for organs at risk. This second LET-based approach can also be used for ions, by changing the LET parameters. GUI screenshots are used to show the input and output parameters for clinical situations used in worked examples from previous publications, where the proton and ion treatments required additional ‘longhand’ calculations. The results from the GUI are in agreement with previously published calculations, but the results are now rapidly available without tedious and error-prone manual computations. The software outputs provide a maximum dose limit boundary, which should not be exceeded. Clinicians may also choose a lower number of treatment fractions, whilst using the same dose per fraction (or conversely a lower dose per fraction but with the same number of fractions) in order to achieve the intended clinical benefit. The new GUI will allow rational estimations of time related radiation tolerance changes in the spinal cord and similar central nervous tissues (optic chiasm, brainstem), which can be used to guide the choice of retreatment dose fractionation schedules.
Is the brain macroscopically linear? A system identification of resting state dynamics
Authors: Nozari Erfan , Bertolero Maxwell A. , Stiso Jennifer , Caciagli Lorenzo , Cornblath Eli J. , He Xiaosong , Mahadevan Arun S. , Pappas George J. , Bassett Dani Smith
Published: December 2020

A central challenge in the computational modeling of neural dynamics is the trade-off between accuracy and simplicity. At the level of individual neurons, nonlinear dynamics are both experimentally established and essential for neuronal functioning. One may therefore expect the collective dynamics of massive networks of such neurons to exhibit an even larger repertoire of nonlinear behaviors. An implicit assumption has thus formed that an “accurate” computational model of whole-brain dynamics must inevitably be non-linear whereas linear models may provide a first-order approximation. To what extent this assumption holds, however, has remained an open question. Here, we provide new evidence that challenges this assumption at the level of whole-brain blood-oxygen-level-dependent (BOLD) and macroscopic field potential dynamics by leveraging the theory of system identification. Using functional magnetic resonance imaging (fMRI) and intracranial electroencephalography (iEEG), we model the spontaneous, resting state activity of 700 subjects in the Human Connectome Project (HCP) and 122 subjects from the Restoring Active Memory (RAM) project using state-of-the-art linear and nonlinear model families. We assess relative model fit using predictive power, computational complexity, and the extent of residual dynamics unexplained by the model. Contrary to our expectations, linear auto-regressive models achieve the best measures across all three metrics. To understand and explain this linearity, we highlight four properties of macroscopic neurodynamics which can counteract or mask microscopic nonlinear dynamics: averaging over space, averaging over time, observation noise, and limited data samples. Whereas the latter two are technological limitations and can improve in the future, the former two are inherent to aggregated macroscopic brain activity. Our results demonstrate the discounted potential of linear models in accurately capturing macroscopic brain dynamics. This, together with the unparalleled interpretability of linear models, can greatly facilitate our understanding of macroscopic neural dynamics, which in turn may facilitate the principled design of model-based interventions for the treatment of neuropsychiatric disorders.
Feasibility of next‐generation sequencing test for patients with advanced NSCLC in clinical practice
Authors: Ariyasu Ryo , Uchibori Ken , Ninomiya Hironori , Ogusu Shinsuke , Tsugitomi Ryosuke , Manabe Ryo , Sakamaoto Hiroaki , Tozuka Takehiro , Yoshida Hiroshi , Amino Yoshiaki , Kitazono Satoru , Yanagitani Noriko , Takeuchi Kengo , Nishio Makoto
Published: December 2020

Background

The usefulness of the Oncomine Dx Target test (Oncomine Dx), a next‐generation sequencing (NGS) test, has already been proven in clinical trials. However, NGS requires high‐quality tumor samples and takes a long time to generate results. The feasibility of NGS for use in advanced non‐small cell lung cancer (NSCLC) patients in clinical practice has not yet been determined.

Methods

Patients serially diagnosed with advanced NSCLC were evaluated in our hospital. The Oncomine Dx, Cobas EGFR mutation test (Cobas EGFR), and ALK‐IHC were performed. The patients were divided into four sets: the full analysis set (FAS) that referred to patients diagnosed with NSCLC, the intent to perform companion diagnostics (CDx) set (IPS) that referred to patients in which CDx had been ordered regardless of sample quality, the per‐performed CDx set (PPS) that referred to patients who could undergo CDx regardless of the results, and the per‐completed CDx set (CCS) that referred to patients in which informative results were received from the CDx.

Results

The total number of patients analyzed in the study was 167. The IPS/FAS of Oncomine Dx (80.2%) was lower than that of the ALK‐IHC (85.0%) and Cobas EGFR (92.8%). The CCS/FAS of Oncomine Dx (65.9%) was lower than that of the ALK‐IHC (82.0%) and Cobas EGFR (92.2%). PPS/IPS and CCS/PPS of the Oncomine Dx with nonsurgical biopsy ranged between 78.6% and 90.9%, which was lower than those patients who underwent surgical resection (95.0% and 100%).

Conclusions

The feasibility of Oncomine Dx in clinical practice was lower than the other CDx. The feasibility of Oncomine Dx will increase by improving the biopsy procedure.

Key points

Significant study findings

The usefulness of a next‐generation sequencing (NGS) test has been proven in clinical trials.

The feasibility of NGS is lower than other diagnostics in clinical practice especially with regard to nonsurgical biopsy.

What this study adds

It is necessary to improve the feasibility of NGS in clinical practice.

To improve NGS feasibility, turnaround time must be shortened, and larger samples must be obtained during surgical procedures.
Toothbrushing frequency and gastric and upper aerodigestive tract cancer risk: A meta‐analysis
Authors: Wu Huadong , Zhang Jinjia , Zhou Baojun
Published: December 2020

Objective

Results of epidemiological studies evaluating the association between toothbrushing and gastric and upper aerodigestive tract (UADT) cancer risk showed inconsistent results. The purpose of this study was to evaluate the association between toothbrushing and gastric and UADT cancer risk and quantify the dose‐response association between them.

Methods

We searched the PubMed, EMBASE and Cochrane Library databases to identify relevant studies on toothbrushing and gastric and UADT cancer risk. Statistical analyses were performed using STATA 12.0 software.

Results

A total of 30 studies of involving 1 194 017 participants met eligibility criteria and were included in the meta‐analysis. Meta‐analysis using a random‐effect model showed that the high frequency of toothbrushing was associated with significantly reduced risk of gastric and UADT cancers (OR: 0.55, 95% CI 0.46‐0.64, P < .05). Our dose‐response analysis presented that every increased toothbrushing per day might reduce oral cavity cancer risk by 6%, pharyngeal cancer risk by 11%, laryngeal cancer risk by 3%, oesophageal cancer risk by 6% and gastric cancer risk by 4%.

Conclusions

This meta‐analysis suggested the negative relationship between frequency of toothbrushing and risk of gastric and UADT cancers. Toothbrushing may be a protective factor for gastric and UADT cancers. However, this association must be further validated through large prospective studies.
Parenting in a Pandemic: Work–Family Arrangements, Well‐Being, and Intimate Relationships Among Adoptive Parents
Authors: Goldberg Abbie E. , McCormick Nora , Virginia Haylie
Published: December 2020

The COVID‐19 pandemic presents unforeseen challenges to families. This mixed‐methods study aimed to address how 89 adoptive parents (lesbian, gay, heterosexual) with school‐age children are navigating a major public health crisis with social, economic, and mental health consequences. Specifically of interest were adoptive parents' worries and concerns; work–family arrangements; and mental, physical, and relational health, in the context of the pandemic and associated quarantine. Findings revealed that 70% of participants had changed work situations, with most newly working from home just as their children initiated remote homeschooling. The division of labor was rarely a source of stress, although the parent who was more involved in homeschooling sometimes experienced resentment. Concerns related to the pandemic included worries about health and children's emotional well‐being and global concerns such as the national economy. Almost half reported declines in mental health (e.g., due to the stress of working and homeschooling), with lesbians being significantly more likely than others to report declines. Declines in physical health were rarer (less than 20%), with more than a quarter reporting improvements (e.g., due to increased exercise). Few reported declines in relationship quality, although almost a quarter reported declines in intimacy. Findings have implications for family and health professionals.
How does the environment influence consumers' perceptions of safety in acute mental health units? A qualitative study
Authors: Cutler Natalie Ann , Halcomb Elizabeth , Sim Jenny , Stephens Moira , Moxham Lorna
Published: December 2020

Aims and objectives

To explore how the physical and social environment of acute mental health units influences consumers' perception and experience of safety.

Background

Acute mental health units are places in which consumers should feel safe. Not all consumers, however, feel safe in this environment. Little is known about what contributes to consumers' feelings of safety in this setting.

Design

The study used a qualitative descriptive design, influenced by naturalistic enquiry. Data were analysed using thematic analysis and are reported according to the COREQ checklist.

Methods

Fifteen people who had experienced admission to an acute mental health unit were individually interviewed.

Results

Having a supportive environment enhanced consumers' perception and experience of safety. A supportive environment was experienced when consumers had privacy, felt safe from other consumers and had meaningful activities to participate in within the acute mental health unit. In contrast, having their privacy breached by other consumers made participants feel unsafe. Many participants were fearful of other consumers, and felt unsafe and unable to protect themselves. Lack of meaningful activities led to boredom and contributed to consumers feeling unsafe.

Conclusions

Personal spaces should address consumers' privacy needs without compromising staff access. Staff presence enhances consumers' feelings of safety, but this need can be heightened when consumers are unable to alert staff when they feel unsafe. Meaningful activities link consumers to their lives outside of the hospital and can enhance recovery.

Relevance to clinical practice

Understanding how the acute unit environment is perceived by consumers can assist nurses and managers to promote feelings of safety among consumers. Feeling safe can, in turn, optimise recovery.
Suppressor Mutations in Type II Secretion Mutants of Vibrio cholerae: Inactivation of the VesC Protease
Authors: Rule Chelsea S. , Park Young-Jun , Delarosa Jaclyn R. , Turley Stewart , Hol Wim G. J. , McColm Sarah , Gura Colby , DiMaio Frank , Korotkov Konstantin V. , Sandkvist Maria
Published: December 2020

Genome-wide transposon mutagenesis has identified the genes encoding the T2SS in
Vibrio cholerae
as essential for viability, but the reason for this is unclear. Mutants with deletions or insertions in these genes can be isolated, suggesting that they have acquired secondary mutations that suppress their growth defect.
Shadow of a disformal Kerr black hole in quadratic degenerate higher-order scalar–tensor theories
Authors: Long Fen , Chen Songbai , Wang Mingzhi , Jing Jiliang
Published: December 2020

We have studied the shadow of a disformal Kerr black hole with an extra deformation parameter, which belongs to non-stealth rotating solutions in quadratic degenerate higher-order scalar–tensor (DHOST) theory. Our result show that the size of the shadow increases with the deformation parameter for the black hole with arbitrary spin parameter. However, the effect of the deformation parameter on the shadow shape depends heavily on the spin parameter of black hole and the sign of the deformation parameter. The change of the shadow shape becomes more distinct for the black hole with the more quickly rotation and the more negative deformation parameter. Especially, for the near-extreme black hole with negative deformation parameter, there exist a “pedicel”-like structure appeared in the shadow, which increases with the absolute value of deformation parameter. The eyebrow-like shadow and the self-similar fractal structures also appear in the shadow for the disformal Kerr black hole in DHOST theory. These features in the black hole shadow originating from the scalar field could help us to understand the non-stealth disformal Kerr black hole and quadratic DHOST theory.
Towards Pedestrian Target Detection with Optimized Mask R-CNN
Authors: Chen Dong-Hao , Cao Yu-Dong , Yan Jia
Published: December 2020

Aiming at the problem of low pedestrian target detection accuracy, we propose a detection algorithm based on optimized Mask R-CNN which uses the latest research results of deep learning to improve the accuracy and speed of detection results. Due to the influence of illumination, posture, background, and other factors on the human target in the natural scene image, the complexity of target information is high. SKNet is used to replace the part of the convolution module in the depth residual network model in order to extract features better so that the model can adaptively select the best convolution kernel during training. In addition, according to the statistical law, the length-width ratio of the anchor box is modified to make it more accord with the natural characteristics of the pedestrian target. Finally, a pedestrian target dataset is established by selecting suitable pedestrian images in the COCO dataset and expanded by adding noise and median filtering. The optimized algorithm is compared with the original algorithm and several other mainstream target detection algorithms on the dataset; the experimental results show that the detection accuracy and detection speed of the optimized algorithm are improved, and its detection accuracy is better than other mainstream target detection algorithms.