bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex Protein Astrogliopathy in an Octogenarian
Authors: Kovacs G.G. , Klotz S. , Fischer P. , Hinterberger M. , Ricken G. , Hönigschnabl S. , Gelpi E.
Published: July 2021

Combination of multiple neurodegenerative proteinopathies is frequent in the elderly. We report the case of an octogenarian who attempted suicide and deceased after hospital admission. Anatomical mapping was performed in several cortical and subcortical brain regions using antibodies against phospho-tau, 4R tau, 3R tau, phospho-TDP-43, ubiquitin, α-synuclein, Aβ and p62. Unexpectedly, histopathologic examination showed prominent subpial, subependymal, grey and white matter, and perivascular aging-related tau astrogliopathy (ARTAG) affecting cortical and subcortical brain regions. This pathology was associated with intermediate Alzheimer’s disease neuropathologic change, cerebral amyloid angiopathy, Lewy-body-type and astroglial synuclein proteinopathy and a multiple system TDP-43 proteinopathy involving also the astroglia. This unusual case of extensive and widespread ARTAG with a complex multiproteinopathy may represent an independent disease entity in the elderly with tau astrogliopathy as the leading force.

Learning Objective

Recognize astroglial protein deposits in neurodegeneration
Somatotroph Adenoma with Dual Transcription Factor Expression
Authors: Pejhan Shervin , VanUum Stan , Duggal Neil , Rotenberg Brian , Mayich Michael , Hammond Robert , Zhang Qi
Published: July 2021

A 20-year-old male presented with evidence of gigantism/acromegaly. Endocrinological investigations identified elevated growth hormone levels and a failed glucose tolerance test. Imaging revealed a macroadenoma expanding the sella with encroachment on the optic chiasm and cavernous sinuses. Trans-sphenoidal resection was undertaken and a gross total removal was achieved. Histopathological features were typical of a densely granulated somatotroph adenoma with abundant growth hormone expression, scattered prolactin expression and sparse examples of fibrous bodies. Unexpectedly, the adenoma not only expressed PIT-1 but also SF-1 transcription factors. This finding suggests that the adenoma may have been pluripotent. The prognostic significance of this finding is uncertain although the patient is stable from an endocrinological and imaging perspective approximately one-year post-op. A pituitary adenoma of this nature has not been previously reported. The recent literature on atypical transcription factor expression patterns and revisions to the classification of pituitary adenomas will be reviewed.

Learning Objectives

Appreciate the rarity of dual transcription factor expression in pituitary adenomas

Rationalize the use of transcription factor characterization in the revised WHO classification of pituitary adenomas
‘A method for safe transmission’: the microscope slides of the American Postal Microscopical Club
Authors: Beiermann Lea
Published: July 2021

In the 1870s, microscopy societies began to proliferate in the United States. Most of these societies attracted microscopists from surrounding cities, but the American Postal Microscopical Club, modelled on the British Postal Microscopical Society, used the postal system to connect microscopists scattered across the country. Club members exchanged microscope slides and notes following a chain-letter system. The main objective of the club was to teach its members how to make permanent slides. Preparation and mounting methods required technical skill, which was, as even club members had to admit, difficult to learn without personal instruction. Yet members developed ways to share craft knowledge through the post. Drawing on the private notes of a member and published reports on the slides circulated, this paper challenges the widespread assumption that the generation of craft knowledge depended on the co-location of artisans. It argues that microscopists’ knowledge of preparation methods was intertwined with their skill in building and navigating information infrastructures, and that by tracing these infrastructures we gain a better understanding of how craft knowledge travelled in the late nineteenth century.
The Apocalyptic Number 616 and the Donatist Church
Authors: HOOVER JESSE
Published: July 2021

The apocalyptic number 616 is attested as a variant for the more common 666 in Revelation xiii.18 as early as Irenaeus as well as in several ancient Greek manuscripts. Surprisingly, however, all known exegetical interpretations of the number in late antiquity and the early medieval era can be traced back to just two sources derived from the Donatist Church in North Africa: Tyconius’ Expositio apocalypseos and the anonymous Liber genealogus. After reviewing these sources and the exegetical traditions predicated on them, this article will introduce a third witness to the 616 variant within the Donatist communion and comment on its implications.
Elusive hypersomnolence in seasonal affective disorder: actigraphic and self-reported sleep in and out of depressive episodes
Authors: Wescott Delainey L. , Franzen Peter L. , Hasler Brant P. , Miller Megan A. , Soehner Adriane M. , Smagula Stephen F. , Wallace Meredith L. , Hall Martica H. , Roecklein Kathryn A.
Published: July 2021

Background

Hypersomnolence has been considered a prominent feature of seasonal affective disorder (SAD) despite mixed research findings. In the largest multi-season study conducted to date, we aimed to clarify the nature and extent of hypersomnolence in SAD using multiple measurements during winter depressive episodes and summer remission.

Methods

Sleep measurements assessed in individuals with SAD and nonseasonal, never-depressed controls included actigraphy, daily sleep diaries, retrospective self-report questionnaires, and self-reported hypersomnia assessed via clinical interviews. To characterize hypersomnolence in SAD we (1) compared sleep between diagnostic groups and seasons, (2) examined correlates of self-reported hypersomnia in SAD, and (3) assessed agreement between commonly used measurement modalities.

Results

In winter compared to summer, individuals with SAD (n = 64) reported sleeping 72 min longer based on clinical interviews (p < 0.001) and 23 min longer based on actigraphy (p = 0.011). Controls (n = 80) did not differ across seasons. There were no seasonal or group differences on total sleep time when assessed by sleep diaries or retrospective self-reports (p's > 0.05). Endorsement of winter hypersomnia in SAD participants was predicted by greater fatigue, total sleep time, time in bed, naps, and later sleep midpoints (p's < 0.05).

Conclusion

Despite a winter increase in total sleep time and year-round elevated daytime sleepiness, the average total sleep time (7 h) suggest hypersomnolence is a poor characterization of SAD. Importantly, self-reported hypersomnia captures multiple sleep disruptions, not solely lengthened sleep duration. We recommend using a multimodal assessment of hypersomnolence in mood disorders prior to sleep intervention.
Special issue on spoken language in time and across time: introduction
Authors: PARADIS CARITA , JOHANSSON VICTORIA , PÕLDVERE NELE
Published: July 2021

The idea of this special issue onSpoken language in time and across timeemerged at an international symposium on this topic that we organised at Lund University on 20 September 2019. The purpose of the symposium was to celebrate important past and present achievements of spoken language research as well as past and present corpora available for such research. Some speakers reported on academic and technical advances from the past, while others offered information about state-of-the-art research on spoken language and spoken corpus compilation. Our idea with the symposium was also to bring together early career scholars, somewhat more senior scholars as well as senior scholars – the latter actually active when interest in spoken language and spoken corpus compilation was in its infancy. The type of spoken corpora in focus extended from the world's first publicly available, machine-readable spoken corpus,The London–Lund Corpus of Spoken English(Svartvik 1990), nowadays referred to as LLC–1, through to the spoken parts ofThe British National Corpora(BNC) from 1994 (BNC Consortium 2007) and 2014 (Loveet al.2017),The Diachronic Corpus of Present-Day Spoken English(DCPSE) consisting of LLC–1 and the British component ofThe International Corpus of English(ICE–GB),Santa Barbara Corpus of Spoken American English(SBCSAE) (Du Boiset al.2000–5),The Corpus of Contemporary American English(COCA) (Davies 2008–) and finally the most recent one,The London–Lund Corpus 2(LLC–2) (Põldvere, Johansson & Paradis 2021a). The symposium thus covered approximately half a century of data from publicly available corpora compiled for multipurpose use by the academic community for research on spoken English in different contexts.
The effect of food insecurity during college on graduation and type of degree attained: evidence from a nationally representative longitudinal survey
Authors: Wolfson Julia A , Insolera Noura , Cohen Alicia J , Leung Cindy W
Published: July 2021

Objective:

To examine the effect of food insecurity during college on graduation and degree attainment.

Design:

Secondary analysis of longitudinal panel data. We measured food insecurity concurrent with college enrollment using the 18-question USDA Household Food Security Survey Module. Educational attainment was measured in 2015-2017 via two questions about college completion and highest degree attained. Logistic and multinomial-logit models adjusted for sociodemographic characteristics were estimated.

Setting:

United States (US)

Participants:

A nationally representative, balanced panel of 1,574 college students in the US in 1999-2003 with follow-up through 2015-2017 from the Panel Study of Income Dynamics.

Results:

In 1999-2003, 14.5% of college students were food insecure and were more likely to be older, non-White, and first-generation students. In adjusted models, food insecurity was associated with lower odds of college graduation (OR 0.57, 95% CI: 0.37, 0.88, p=0.01) and lower likelihood of obtaining a Bachelor’s degree (RRR 0.57 95% CI: 0.35, 0.92, p=0.02) or graduate/professional degree (RRR 0.39, 95% CI: 0.17, 0.86, p=0.022). These associations were more pronounced among first-generation students. 47.2% of first-generation students who experienced food insecurity graduated from college; food insecure first-generation students were less likely to graduate compared to first-generation students who were food secure (47.2% vs. 59.3%, p=0.020) and non-first-generation students who were food insecure (47.2% vs. 65.2%, p=0.037).

Conclusions:

Food insecurity during college is a barrier to graduation and higher degree attainment, particularly for first-generation students. Existing policies and programs that help mitigate food insecurity should be expanded and more accessible to the college student population.
ITGB1 Enhances the Proliferation, Survival, and Motility in Gastric Cancer Cells
Authors: Cheng Sinan , Li Xinyao , Yuan Yue , Jia Chenshuang , Chen Lirong , Gao Qian , Lu Zheng , Yang Ruina , Nie Guochao , Yang Jin , Duan Wei , Xiao Li , Hou Yingchun
Published: July 2021

ITGB1 (Integrin β1, CD29) is a member of the integrin family and has a role as a major adhesion receptor. Gastric cancer (GC) is an important cause of mortality worldwide, especially in China. As a potential cancer enhancer, the role ITGB1 plays in GC progression remains unclear. In the current study, our assay on the databases of tumoassociated gene expression and interaction found that the high expression of ITGB1 was closely correlated with the poor prognosis of GC patients. To explore the roles, ITGB1 plays in GC progression, and an ITGB1-deleted cell line (ITGB1−/−SGC7901) was generated using the CRISPR/Cas9 method. The tumor malignancy-associated cell behaviors and microstructures were detected, imaged, and analyzed using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), wound healing, transwell, scanning electron microscopy, laser scanning confocal microscopy, and others. The results indicated that ITGB1 deletion decreased the GC cell proliferation and motility, and inhibited motility-relevant microstructures, such as pseudopodia and filopodia, markedly in ITGB1-deleted SGC7901 cells. The analysis of STRING database and western blots indicated that ITGB1 contributes to the malignancy of GC mediated by Src-mediated FAK/PI3K/Akt signaling pathways. Taken together, the results showed that ITGB1 may be a potential targeting marker for GC diagnosis and therapy in the future.
Insecurity and the reintegration of former armed non-state actors in Colombia
Authors: Meernik James , Gaviria Henao Juan , Baron-Mendoza Laura
Published: July 2021

In this paper, we focus on the completion of a government reintegration program in Colombia for former non-state armed actors, such as rebel forces and militias, in the post-conflict period. As the members of these groups lay down their arms and return to a peaceful existence, the effectiveness of their transition to ‘normal’ lives can be critical in preventing the re-emergence of conflict and violence. Former combatants face numerous challenges and hardships such as criminal violence, political violence, economic hardship that, if not properly addressed, may increase the likelihood that some of them become involved in criminal work, political violence, or other activities that undermine peace. We develop a theory of the impact of violence and insecurity challenges facing former, non-state armed actors (henceforth, ANSAs). We suggest that the numerous challenges involved in leading a normal life under conditions of abnormal security will likely make successful completion of government reintegration programs more difficult for ANSAs. We also consider and account for the powerful effects of gender and family in the successful completion of a reintegration program. We test our theoretical model on the successful completion of a government reintegration program in Colombia, and test our hypotheses on a large database of ANSAs. We find support for our hypotheses, as well as social factors that greatly influenced the likelihood of successful completion of the Colombian government’s reintegration program.
Private Processes and Public Values: Disciplining Trade in Forest and Ecosystem Risk Commodities via Non-Financial Due Diligence
Authors: Partiti Enrico
Published: July 2021

This article takes stock of the many private and public instruments enacted transnationally to tackle the pressing problem of deforestation, ecosystem conversion, and associated human rights violations caused by international demand for and trade in agricultural commodities. The article argues that non-financial due diligence based on no-conversion criteria, and in line with the United Nations Guiding Principles on Business and Human Rights, holds considerable potential for ensuring deforestation-free value chains by enrolling and scaling up firm-level supply-chain management systems and private standards. The article introduces the main features of a possible European Union measure that disciplines via non-financial due diligence the placing on the market of commodities and products associated with deforestation, ecosystem conversion, degradation of forests and ecosystems, and associated human rights violations. Such a measure would also have the effect of streamlining initiatives enacted by private authority.
Association Between Cognitive Decline and Oral Health Status in the Aging Population
Authors: Bumb Swapnil Sunil , Govindan Charu Chitra , Kadtane Safalya S. , Chawla Roshani , Gupta Ruchika , Khoriya Sarvesh S.
Published: July 2021

Abstract. Background: To date, no longitudinal prospective study has investigated the association between oral health status and cognitive decline in the geriatric Indian population, possibly because past studies differed in their target groups and methodologies. We investigated the association between tooth loss, as evaluated through clinical oral examinations, and the development of cognitive decline in older adults while considering baseline cognitive function. Objectives: This study served to find an association between oral health status and the subsequent development of cognitive decline in older adults of Maharashtra state while considering baseline cognitive function. Material and Methods: This 5-year prospective cohort study followed 140 participants without cognitive impairment aged ≥ 65 years (mean age: 70.9 ± 4.3 years) living in the Dhule region of Maharashtra, India. Cognitive function was evaluated with the Mini-Mental State Examination (MMSE) in baseline and follow-up surveys, while oral health examination was carried out using Oral Hygiene Index. To investigate the association between oral health status and cognitive decline, we applied a multiple logistic regression analysis adjusted for age, sex, hypertension, diabetes, cerebrovascular/cardiovascular disease, hypercholesterolemia, depressive symptoms, body mass index, smoking status, drinking status, duration of education, and baseline MMSE score. Results: In the 5 years after the baseline survey, we obtained an overall incidence of 20.71% in the population that developed cognitive decline (i.e., MMSE scores of ≤ 24). A multivariable logistic regression analysis indicated that participants with compromised oral health were more likely to develop cognitive decline than those with mild to moderate oral health were (odds ratio: 3.31; 95% confidence interval: 1.07–10.2). Age, male sex, and baseline MMSE scores were also significantly associated with cognitive decline. Conclusion: Among the geriatric population of India, poor oral health status was independently associated with the development of cognitive decline within 5 years. This finding corroborates the hypothesis that oral health may be a predictor or risk factor for cognitive decline.
Threats to Professional Roles in Part-Time Leadership
Authors: Rynek Mona , Ellwart Thomas , Peiffer Henrike , Endres Elisabeth , Moldzio Thomas
Published: July 2021

Abstract. Leaders working part time struggle with a lack of respect and acceptance from their subordinates and their management colleagues. Leadership as a part-time role does not match the traditional expectation of leaders being omnipresent and always responsive (Jochmann-Döhl, 2017). Although leaders working part time (LPT) are supported by subordinates and colleagues, their supportive behavior is often coupled with accusations that work-related problems occur only because the leader is working part time. According to the stress-as-offense-to-self theory (SOS, Semmer et al., 2007 ; Semmer et al., 2019 ), such dysfunctional supportive behavior triggers threats by offending the need for belonging. This study serves to strengthen SOS theory and extend its application beyond stress research by investigating the effects of LPT threat experiences on rumination, LPT job satisfaction, and role identification. Further, it empirically confirms the need-based threat mechanism. Results based on an online questionnaire ( N = 101 LPT) show that dysfunctional support by subordinates and management colleagues relates to a feeling of exclusion by significant others as an indicator of an offended need for belonging. Furthermore, the results indicate that the feeling of exclusion mediates the relationship between dysfunctional support and role identification and between dysfunctional support and LPT job satisfaction. No mediation effect was found for rumination. In addition to providing a theoretically differentiated understanding and prediction of threats, the study includes important practical starting points for the risk management of LPT.
Variability in Indonesian Throughflow Upper Hydrology in Response to Precession‐Induced Tropical Climate Processes Over the Past 120 kyr
Authors: Zhang Peng , Xu Jian , Beil Sebastian , Holbourn Ann , Kuhnt Wolfgang , Li Tiegang , Xiong Zhifang , Yan Hong , Cui Rui , Liu Heng , Wu Hanning
Published: July 2021

The Indonesian Throughflow (ITF), as the sole low‐latitude conduit connecting the Pacific and Indian Oceans, regulates the thermohaline balance between these oceans. Thus, investigating the variability in the ITF and its relationship with the precessional forcing is crucial for understanding the drivers of tropical climate change. Here, we reconstruct the history of the ITF over the past ∼120 kyr based on high‐resolution (∼400 years) δ18O and Mg/Ca records of Globigerinoides ruber and Pulleniatina obliquiloculata from core SO217‐18540 retrieved from the Flores Sea upwelling region within the main pathway of the ITF. A comparison of these new records with published paleo‐oceanographic and climatological data from the western tropical Pacific Ocean suggests that annual mean conditions in the Flores Sea were controlled by ITF variability rather than by monsoonal upwelling. Our results further indicate that precessional insolation was a major forcing for the hydrological evolution of the ITF during the past 120 kyr. We suggest that the precessional insolation forcing paced ITF variability by modulating the mean state of El Niño‐Southern Oscillation‐like conditions and latitudinal shifts and/or expansion/contraction of the Intertropical Convergence Zone.
Exploring the Dramatic Shift in Ice Age Duration
Authors: Berends Constantijn , van de Wal Roderik , Lourens Lucas
Published: July 2021

Scientists are still seeking an explanation for the Mid-Pleistocene Transition when ice ages became longer in duration and exploring what it may mean for future climate change.
Crustal SiO2 Content of the Emeishan Large Igneous Province and its Implications for Magma Volume and Plumbing System
Authors: Li Wei , Chen Yun , Xu Yi‐Gang
Published: July 2021

The Permian Emeishan large igneous province (LIP) in Southwestern China is recognized as a remnant of mantle plume activity. Its crust composition has a significant bearing on understanding the magmatic plumbing system in a LIP and the volume of magmas generated, which is critical to the viability of the mantle plume model and its potential environmental impact but is difficult to constrain. Here, a SiO2‐VP/VS‐VS relationship, compiled from existing laboratory measurements, is used to estimate the crustal SiO2 content of the Emeishan LIP based on the joint constraint of the crustal bulk VP/VS ratio and average VS. The crust underneath the northeastern inner zone of the Emeishan LIP has a SiO2 content of ∼55.7 wt%, in contrast with the bulk continental crust's SiO2 content of 62.1 ± 2.1 wt% but largely overlapping with the exposed mafic‐ultramafic intrusions. Such an unusually “mafic” crust is attributable to the intensive magmatic underplating and intraplating associated with the Emeishan mantle plume. It further allows a minimum estimate of the volume of ∼1.45 × 106 km3 for erupted magmas and ∼2.39 × 106 km3 for total emplaced magmas, which is comparable to the volume of typical plume‐generated LIPs.
The Role of Strong Meridional Neutral Winds in the Formation of Deep Equatorial Ionization Trough in CHAMP Observations
Authors: Tian Yaoyu , Hao Yongqiang , Li Quanhan , Guo Jianguang , Zhang Xiaoxin , Zhang Donghe , Xiao Zuo
Published: July 2021

Ionospheric plasma density data from the Planar Langmuir Probe onboard the CHAllenging Minisatellite Payload (CHAMP) are used to investigate the latitudinal profile of the ionospheric plasma density. Along with the well‐known profiles with features of the equatorial ionization anomaly and equatorial plasma bubbles, a third type is observed as smooth profiles with large‐scale deep equatorial trough (DET) where the plasma density is extremely low. A global survey focusing on magnetically quiet conditions reveals that the DET profiles are generally a post‐sunset phenomenon, and their appearance depends on longitude and season. During equinoxes in active solar years, the strong pre‐reversal enhancement electric field is believed to uplift the ionosphere and produce the DET profiles. While around June solstice, the DET profiles are clustered at W– E longitude, where the zonal electric field is weak but the magnetic meridional component of the neutral wind is most significant. The SAMI2 model is then employed to simulate the ionospheric plasma distribution in the magnetic meridional plane with enhanced neutral wind, which successfully reproduced the main features of the observed DET profile. The results indicate that the neutral wind can obviously affect the equatorial ionosphere by transporting plasma in the magnetic flux tube through neutral‐ion interaction. The neutral wind is previously known to work with the inclined magnetic field at mid‐latitude, while this study emphasizes its effect around the magnetic equator especially when the electric field forcing () is weak or absent.
Characterization of Wind‐Blown Sand With Near‐Wall Motions and Turbulence: From Grain‐Scale Distributions to Sediment Transport
Authors: Jin Ting , Wang Ping , Zheng Xiaojing
Published: July 2021

The impact and lift‐off parameters of particles play a key role in the understanding of the saltation mechanisms in aeolian environment. However, limitations of experimental instruments and numerical simulation may result in unreliable motion parameters near the bed surface. Here, we report on the impact and lift‐off parameters of saltating particles in wind‐blown sand predicted with Reynolds‐averaged Navier–Stokes (RANS) or large eddy simulation (LES) and the three‐dimensional stochastic particle‐bed collision model. Simulation results showed new phenomena, including: (a) a reduced mean impact velocity and an increased probability of lift‐off velocities distribution at left extreme with increasing free stream velocity, and (b) two peaks of the impact angle distribution. These phenomena disappear when the statistical height is increased to five times the particle diameter, suggesting that the near‐wall motions are not negligible. In addition, when turbulence is considered and wind velocity increases, the extreme value of velocity distribution increases, impact angle distribution shows a longer tail, and mean impact and lift‐off parameters increase (except impact velocity). We conclude that new velocity distribution with near‐wall motions and turbulence will significantly improve the prediction of aeolian transport flux.
Evaluation of the New Background Covariance Model for the Ionospheric Data Assimilation
Authors: Forsythe Victoriya V. , Azeem Irfan , Blay Ryan , Crowley Geoff , Gasperini Federico , Hughes Joe , Makarevich Roman A. , Wu Wanli
Published: July 2021

This paper presents the evaluation of the recently developed covariance model for the Ionospheric Data Assimilation Four‐Dimensional (IDA4D) technique. The ionospheric data are generated using the Observation System Simulation Experiment Tool from the known ionospheric state produced by the physics‐based Thermosphere‐Ionosphere‐Mesosphere Electrodynamics General Circulation Model. Several experiments are conducted to assess performance of IDA4D with data‐driven vertical and horizontal covariance matrices. We show that the vertical part of the covariance model plays the most important role because it preserves the vertical structure of the F‐region density layer and helps to correct a tomographic issue that arises when the slant total electron content is assimilated along the intersecting rays. The results show that the new covariance model improves the fidelity of IDA4D algorithm, making it more suitable for the regional assimilation with dense ground‐based Global Positioning System data coverage.
In Memoriam
Authors: Anonymous
Published: July 2021

William B. Joyner died on March 30, 2001, at age 70. He had been an AGU member (Seismology) since 1953.

Bradford Sturtevant died in October 2000, at age 67. He had been an AGU member (Volcanology Geochemistry, Petrology) since 1985.
Errors in the implementation, analysis, and reporting of randomization within obesity and nutrition research: a guide to their avoidance
Authors: Vorland Colby J. , Brown Andrew W. , Dawson John A. , Dickinson Stephanie L. , Golzarri-Arroyo Lilian , Hannon Bridget A. , Heo Moonseong , Heymsfield Steven B. , Jayawardene Wasantha P. , Kahathuduwa Chanaka N. , Keith Scott W. , Oakes J. Michael , Tekwe Carmen D. , Thabane Lehana , Allison David B.
Published: July 2021

Randomization is an important tool used to establish causal inferences in studies designed to further our understanding of questions related to obesity and nutrition. To take advantage of the inferences afforded by randomization, scientific standards must be upheld during the planning, execution, analysis, and reporting of such studies. We discuss ten errors in randomized experiments from real-world examples from the literature and outline best practices for their avoidance. These ten errors include: representing nonrandom allocation as random, failing to adequately conceal allocation, not accounting for changing allocation ratios, replacing subjects in nonrandom ways, failing to account for non-independence, drawing inferences by comparing statistical significance from within-group comparisons instead of between-groups, pooling data and breaking the randomized design, failing to account for missing data, failing to report sufficient information to understand study methods, and failing to frame the causal question as testing the randomized assignment per se. We hope that these examples will aid researchers, reviewers, journal editors, and other readers to endeavor to a high standard of scientific rigor in randomized experiments within obesity and nutrition research.
A comprehensive review on biomarkers associated with painful temporomandibular disorders
Authors: Shrivastava Mayank , Battaglino Ricardo , Ye Liang
Published: July 2021

Pain of the orofacial region is the primary complaint for which patients seek treatment. Of all the orofacial pain conditions, one condition that possess a significant global health problem is temporomandibular disorder (TMD). Patients with TMD typically frequently complaints of pain as a symptom. TMD can occur due to complex interplay between peripheral and central sensitization, endogenous modulatory pathways, and cortical processing. For diagnosis of TMD pain a descriptive history, clinical assessment, and imaging is needed. However, due to the complex nature of pain an additional step is needed to render a definitive TMD diagnosis. In this review we explicate the role of different biomarkers involved in painful TMD. In painful TMD conditions, the role of biomarkers is still elusive. We believe that the identification of biomarkers associated with painful TMD may stimulate researchers and clinician to understand the mechanism underlying the pathogenesis of TMD and help them in developing newer methods for the diagnosis and management of TMD. Therefore, to understand the potential relationship of biomarkers, and painful TMD we categorize the biomarkers as molecular biomarkers, neuroimaging biomarkers and sensory biomarkers. In addition, we will briefly discuss pain genetics and the role of potential microRNA (miRNA) involved in TMD pain.
Differential immune responses in pregnant patients recovered from COVID-19
Authors: Chen Ge , Zhang Yiming , Zhang Yaoyao , Ai Jihui , Yang Bin , Cui Mengge , Liao Qiuyue , Chen Hanxiao , Bai Hualin , Shang Dashing , Chen Jing , Sun ChaoYang , Liu Haiyi , Liu Fengyuan , Mao Bin , Sun Guoqiang , Chen Lu , Lin Jing-wen , Li Kezhen
Published: July 2021

Pregnant women are generally more susceptible to viral infection. Although the impact of SARS-CoV-2 in pregnancy remains to be determined, evidence indicates that the risk factors for severe COVID-19 are similar in pregnancy to the general population. Here we systemically analyzed the clinical characteristics of pregnant and non-pregnant female COVID-19 patients who were hospitalized during the same period and found that pregnant patients developed marked lymphopenia and higher inflammation evident by higher C-reactive protein and IL-6. To elucidate the pathways that might contribute to immunopathology or protective immunity against COVID-19 during pregnancy, we applied single-cell mRNA sequencing to profile peripheral blood mononuclear cells from four pregnant and six non-pregnant female patients after recovery along with four pregnant and three non-pregnant healthy donors. We found normal clonal expansion of T cells in the pregnant patients, heightened activation and chemotaxis in NK, NKT, and MAIT cells, and differential interferon responses in the monocyte compartment. Our data present a unique feature in both innate and adaptive immune responses in pregnant patients recovered from COVID-19.
Tubulointerstitial nephritis and uveitis in Northern Ireland
Authors: Heaney A. , McLoone E. , Williams M. , Silvestri G. , Courtney A. E. , O’Rourke D. , McAvoy C. E.
Published: July 2021

Objectives

This paper looks at patients with a diagnosis of tubulointerstitial nephritis and uveitis (TINU) presenting to the Northern Ireland regional adult and paediatric uveitis service in the Belfast Health and Social Care Trust. The demographic distribution, treatment required and the visual and renal outcomes of these patients are documented.

Methods

Data were collected retrospectively on 24 patients with TINU using the Northern Ireland Electronic Care Record, central pathology records alongside the adult and paediatric uveitis databases from 2011 to 2021. Patients were categorised into two groups using the Mandeville classification system. Standard Uveitis Nomenclature (SUN) was used to classify the uveitis.

Results

The population prevalence is at least 12.6 cases per million based on a population of 1.9 million. Nineteen of 24 cases were definite TINU and five of 24 probable. Seventeen out of 24 had biopsy-positive TIN, all of which met all of the Mandeville clinical diagnostic features required for a definite diagnosis. All but one presented with acute bilateral anterior uveitis. The paediatric cases ranged from age 12 to 18 at age of onset with a mean age of 14. Of the 18 adult onset cases, the age ranged from 20 to 76 years. The mean age of onset for the adult cases was 53 years. Of these patients 71% were female; 42% required second-line immunosuppression for ocular disease. Visual acuity was maintained. Follow-up time ranged from 3 months to 16 years. No patient developed long-term renal impairment.

Conclusions

TINU is a cause of uveitis in both the paediatric and adult populations. In Northern Ireland average age with TINU was older than much of the published literature. Long-term immunosuppression for uveitis may be required as ongoing ocular, rather than renal inflammation seemed to require treatment.
Clustering and control for adaptation uncovers time-warped spike time patterns in cortical networks in vivo
Authors: Isbister James B. , Reyes-Puerta Vicente , Sun Jyh-Jang , Horenko Illia , Luhmann Heiko J.
Published: July 2021

How information in the nervous system is encoded by patterns of action potentials (i.e. spikes) remains an open question. Multi-neuron patterns of single spikes are a prime candidate for spike time encoding but their temporal variability requires further characterisation. Here we show how known sources of spike count variability affect stimulus-evoked spike time patterns between neurons separated over multiple layers and columns of adult rat somatosensory cortex in vivo. On subsets of trials (clusters) and after controlling for stimulus-response adaptation, spike time differences between pairs of neurons are “time-warped” (compressed/stretched) by trial-to-trial changes in shared excitability, explaining why fixed spike time patterns and noise correlations are seldom reported. We show that predicted cortical state is correlated between groups of 4 neurons, introducing the possibility of spike time pattern modulation by population-wide trial-to-trial changes in excitability (i.e. cortical state). Under the assumption of state-dependent coding, we propose an improved potential encoding capacity.
Discovery of a tsunami deposit from the Bronze Age Santorini eruption at Malia (Crete): impact, chronology, extension
Authors: Lespez Laurent , Lescure Séverine , Saulnier-Copard Ségolène , Glais Arthur , Berger Jean-François , Lavigne Franck , Pearson Charlotte , Virmoux Clément , Müller Celka Sylvie , Pomadère Maia
Published: July 2021

A geomorphological survey immediately west of the Minoan town of Malia (Crete) shows that a tsunami resulting from the Bronze Age Santorini eruption reached the outskirts of the Palatial center. Sediment cores testify a unique erosional event during the Late Minoan period, followed locally by a high energy sand unit comprising marine fauna. This confirms that a tsunami impacted northern Crete and caused an inundation up to 400 m inland at Malia. We obtained a radiocarbon range of 1744–1544 BCE for the secure pre-tsunami context and an interval 1509–1430 BCE for the post-event layer. Examination of tsunami deposits was used to constrain run-up not exceeding 8 m asl. The results open the field for new research on the Bronze Age Santorini tsunami regarding both impact and consequences for the Minoan civilization.
Dialysis adequacy predictions using a machine learning method
Authors: Kim Hyung Woo , Heo Seok-Jae , Kim Jae Young , Kim Annie , Nam Chung-Mo , Kim Beom Seok
Published: July 2021

Dialysis adequacy is an important survival indicator in patients with chronic hemodialysis. However, there are inconveniences and disadvantages to measuring dialysis adequacy by blood samples. This study used machine learning models to predict dialysis adequacy in chronic hemodialysis patients using repeatedly measured data during hemodialysis. This study included 1333 hemodialysis sessions corresponding to the monthly examination dates of 61 patients. Patient demographics and clinical parameters were continuously measured from the hemodialysis machine; 240 measurements were collected from each hemodialysis session. Machine learning models (random forest and extreme gradient boosting [XGBoost]) and deep learning models (convolutional neural network and gated recurrent unit) were compared with multivariable linear regression models. The mean absolute percentage error (MAPE), root mean square error (RMSE), and Spearman’s rank correlation coefficient (Corr) for each model using fivefold cross-validation were calculated as performance measurements. The XGBoost model had the best performance among all methods (MAPE = 2.500; RMSE = 2.906; Corr = 0.873). The deep learning models with convolutional neural network (MAPE = 2.835; RMSE = 3.125; Corr = 0.833) and gated recurrent unit (MAPE = 2.974; RMSE = 3.230; Corr = 0.824) had similar performances. The linear regression models had the lowest performance (MAPE = 3.284; RMSE = 3.586; Corr = 0.770) compared with other models. Machine learning methods can accurately infer hemodialysis adequacy using continuously measured data from hemodialysis machines.
Effects of different returning method combined with decomposer on decomposition of organic components of straw and soil fertility
Authors: Wang Xiao , Wang Xuexin , Geng Peng , Yang Qian , Chen Kun , Liu Ning , Fan Yueling , Zhan Xiumei , Han Xiaori
Published: July 2021

In view of the problems of low straw decomposition rates and reduced soil fertility in southern Liaoning, China, we investigated the effects of no-tillage mode (NT), deep loosening + deep rotary tillage mode (PT), rotary tillage mode (RT) and the addition of decomposing agent (the next is called a decomposer) (NT + S, PT + S, RT + S) on the decomposition proportion of straw, respectively, by using the nylon net bag method in combination with 365-day field plot experiments. The decomposition rules of cellulose, hemicellulose and lignin as well as the dynamics of soil organic carbon (SOC), soil microbial biomass carbon (MBC) and soil dissolved organic carbon (DOC) in straw returned to the field for 15, 35, 55, 75, 95, 145 and 365 days were analyzed. The results showed that in the short term, the decomposition of straw was better in both the rotray tillage and deep loosening + deep rotary modes than in the no-tillage mode, and the addition of decomposer significantly promoted the decomposition of straw and the release of carbon from straw, among them, the RT + S treatment had the highest straw decomposition proportion and carbon release proportion in all sampling periods. After a one year experimental cycle, the RT + S treatment showed the highest proportion of cellulose, hemicellulose and lignin decomposition with 35.49%, 84.23% and 85.50%, respectively, and soil SOC, MBC and DOC contents were also higher than the other treatments with an increase of 2.30 g kg−1, 14.22 mg kg−1 and 25.10 mg kg−1, respectively, compared to the pre-experimental soil. Our results show that in the short term, to accelerate the decomposition rate of returned straw and increase the content of various forms of carbon in soil, rotary tillage can be used to return the straw to the field, while also spraying straw decomposer on its surface. This experiment used a new straw decomposer rich in a variety of microorganisms, combined with the comparison of a variety of straw return modes, and in-depth study of straw decomposition effects of cellulose, hemicellulose and lignin. Thus, a scheme that can effectively improve the decomposition rate of straw and the content of various forms of organic carbon in soil within a short period of time was explored to provide theoretical support for the southern Liaoning.
Citizens and scientists collect comparable oceanographic data: measurements of ocean transparency from the Secchi Disk study and science programmes
Authors: Kirby Richard R. , Beaugrand Gregory , Kleparski Loick , Goodall Susie , Lavender Samantha
Published: July 2021

Marine phytoplankton accounts for approximately 50% of all photosynthesis on Earth, underpins the marine food chain and plays a central role in the Earth’s biogeochemical cycles and climate. In situ measurements of ocean transparency can be used to estimate phytoplankton biomass. The scale and challenging conditions of the ocean make it a difficult environment for in situ studies, however. Here, we show that citizen scientists (seafarers) using a simple white Secchi Disk can collect ocean transparency data to complement formal scientific efforts using similar equipment. Citizen scientist data can therefore help understand current climate-driven changes in phytoplankton biomass at a global scale.
Sensitive assay design for detection of anti-drug antibodies to biotherapeutics that lack an immunoglobulin Fc domain
Authors: Johnson Derrick , Simmons Erica , Abdeen Sanofar , Kinne Adam , Parmer Elijah , Rinker Sherri , Thystrup Jennifer , Ramaswamy Swarna , Bowsher Ronald R.
Published: July 2021

Today the evaluation of unwanted immunogenicity is a key component in the clinical safety evaluation of new biotherapeutic drugs and macromolecular delivery strategies. However, the evolving structural complexity in contemporary biotherapeutics creates a need for on-going innovation in assay designs for reliable detection of anti-drug antibodies, especially for biotherapeutics that may not be well-suited for testing by a bridging assay. We, therefore, initiated systematic optimization of the direct binding assay to adapt it for routine use in regulatory-compliant assays of serum anti-drug antibodies. Accordingly, we first prepared a SULFO-TAG labeled conjugate of recombinant Protein-A/G to create a sensitive electrochemiluminescent secondary detection reagent with broad reactivity to antibodies across many species. Secondly, we evaluated candidate blocker-diluents to identify ones producing the highest signal-to-noise response ratios. Lastly, we introduced use of the ratio of signal responses in biotherapeutic-coated and uncoated wells as a data transformation strategy to identify biological outliers. This alternative data normalization approach improved normality, reduced skewness, and facilitated application of a parametric screening cut point. We believe the optimized direct binding assay design employing SULFO-TAG labeled Protein-A/G represents a useful analytical design for detecting serum ADA to biotherapeutics that lack an immunoglobulin Fc domain.
Anisotropy in mechanical unfolding of protein upon partner-assisted pulling and handle-assisted pulling
Authors: Arora Nisha , Hazra Jagadish Prasad , Rakshit Sabyasachi
Published: July 2021

Proteins as force-sensors respond to mechanical cues and regulate signaling in physiology. Proteins commonly connect the source and response points of mechanical cues in two conformations, independent proteins in end-to-end geometry and protein complexes in handshake geometry. The force-responsive property of independent proteins in end-to-end geometry is studied extensively using single-molecule force spectroscopy (SMFS). The physiological significance of the complex conformations in force-sensing is often disregarded as mere surge protectors. However, with the potential of force-steering, protein complexes possess a distinct mechano-responsive property over individual force-sensors. To decipher, we choose a force-sensing protein, cadherin-23, from tip-link complex and perform SMFS using end-to-end geometry and handshake complex geometry. We measure higher force-resilience of cadherin-23 with preferential shorter extensions in handshake mode of pulling over the direct mode. The handshake geometry drives the force-response of cadherin-23 through different potential-energy landscapes than direct pulling. Analysis of the dynamic network structure of cadherin-23 under tension indicates narrow force-distributions among residues in cadherin-23 in direct pulling, resulting in low force-dissipation paths and low resilience to force. Overall, the distinct and superior mechanical responses of cadherin-23 in handshake geometry than single protein geometry highlight a probable evolutionary drive of protein-protein complexes as force-conveyors over independent ones.
FIP200 restricts RNA virus infection by facilitating RIG-I activation
Authors: Wang Lingyan , Song Kun , Hao Wenzhuo , Wu Yakun , Patil Girish , Hua Fang , Sun Yiwen , Huang Chaoqun , Ritchey Jerry , Jones Clinton , Liu Lin , Guan Jun-Lin , Li Shitao
Published: July 2021

Retinoic acid-inducible gene I (RIG-I) senses viral RNA and instigates an innate immune signaling cascade to induce type I interferon expression. Currently, the regulatory mechanisms controlling RIG-I activation remain to be fully elucidated. Here we show that the FAK family kinase-interacting protein of 200 kDa (FIP200) facilitates RIG-I activation. FIP200 deficiency impaired RIG-I signaling and increased host susceptibility to RNA virus infection. In vivo studies further demonstrated FIP200 knockout mice were more susceptible to RNA virus infection due to the reduced innate immune response. Mechanistic studies revealed that FIP200 competed with the helicase domain of RIG-I for interaction with the two tandem caspase activation and recruitment domains (2CARD), thereby facilitating the release of 2CARD from the suppression status. Furthermore, FIP200 formed a dimer and facilitated 2CARD oligomerization, thereby promoting RIG-I activation. Taken together, our study defines FIP200 as an innate immune signaling molecule that positively regulates RIG-I activation.
Simulation of nitrogen nuclear spin magnetization of liquid solved nitroxides
Authors: Marko Andriy , Sojka Antonin , Laguta Oleksii , Neugebauer Petr
Published: July 2021

Simulated nitrogen nuclear spin magnetization generated by RF and MW irradiation of liquid solved nitroxides.
Rapid colorimetric analysis of multiple microRNAs using encoded hydrogel microparticles
Authors: Kim Ju Yeon , Mun Seok Joon , Roh Yoon Ho , Bong Ki Wan
Published: July 2021

A schematic of rapid colorimetric analysis of microRNA based on hydrogel microparticles.
Enhanced thread spray mass spectrometry: a general method for direct pesticide analysis in various complex matrices
Authors: Jackson Sierra , Badu-Tawiah Abraham K.
Published: July 2021

Cellulose thread substrates enable sampling and direct mass spectrometry analysis of structurally different pesticides from various matrices without sample preparation.