bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of fluoroquinolones or cephalosporin plus macrolide with Clostridioides difficile infection (CDI) after treatment for community-acquired pneumonia
Authors: Patel Preethi , Deshpande Abhishek , Yu Pei-Chun , Imrey Peter B. , Lindenauer Peter K. , Zilberberg Marya D. , Haessler Sarah , Rothberg Michael B.
Published: April 2022

Objective:

Clostridioides difficile infection (CDI) is the most common cause of gastroenteritis, and community-acquired pneumonia (CAP) is the most common infection treated in hospitals. American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) CAP guidelines recommend empiric therapy with a respiratory fluoroquinolone or cephalosporin plus macrolide combination, but the CDI risk of these regimens is unknown. We examined the association between each antibiotic regimen and the development of hospital-onset CDI.

Methods:

We conducted a retrospective cohort study using data from 638 US hospitals contributing administrative including 177 also contributing microbiologic data to Premier, Inc. We included adults admitted with pneumonia and discharged from July 2010 through June 2015 with a pneumonia diagnosis code who received ≥3 days of either empiric regimen. Hospital-onset CDI was defined by a diagnosis code not present on admission and positive laboratory test on day 4 or later or readmission for CDI. Mixed propensity-weighted multiple logistic regression was used to estimate the associations of CDI with antibiotic regimens.

Results:

Our sample included 58,060 patients treated with either cephalosporin plus macrolide (36,796 patients) or a fluoroquinolone alone (21,264 patients) and with microbiological data; 127 (0.35%) patients who received cephalosporin plus macrolide and 65 (0.31%) who received a fluoroquinolone developed CDI. After adjustment for patient demographics, comorbidities, risk factors for antimicrobial resistance, and hospital characteristics, CDI risks were similar for fluoroquinolones versus cephalosporin plus macrolide (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.70–1.38).

Conclusion:

Among patients with CAP at US hospitals, CDI was uncommon, occurring in ∼0.33% of patients. We did not detect a significant association between the choice of empiric guideline recommended antibiotic therapy and the development of CDI.
Fossilized pollen malformations as indicators of past environmental stress and meiotic disruption: insights from modern conifers
Authors: Benca Jeffrey P. , Duijnstee Ivo A. P. , Looy Cindy V.
Published: April 2022

Pollen malformations have been proposed as a paleoenvironmental stress proxy. However, the frequency and variability of pollen malformations under near-optimal conditions and environmental stress, as well as their developmental origins, remain unclear. To bridge these gaps, we compared pollen malformation frequencies and assemblages of 14 extant conifer genera of Pinaceae and Podocarpaceae producing saccate (winged) grains grown under near-optimal conditions. These baseline pollen yields were compared with those produced byPinus mugo‘Columnaris’ cultured under an abiotic stress—three experimentally heightened ultraviolet-B radiation (UV-B) regimes proposed for the end-Permian crisis. We additionally reviewed previous cytological literature of abnormal microsporogenesis in conifers. Under near-optimal conditions, malformations comprise <3% of pollen yields in 12 out of 13 bisaccate genera and >10% of yields in the naturally trisaccateDacrycarpus dacrydioides. We detected no phylogenetic pattern in malformation assemblages of the baseline comparisons. UV-B–irradiatedP. mugoproduced significantly higher malformation frequencies and different assemblage compositions when compared with baseline bisaccate lineages. We propose that pollen malformations originate during the meiotic and tetrad stages of microsporogenesis and present a framework for the ontogeny of different malformation types seen in the fossil record. Malformations comprising >3% of bisaccate pollen yields can be used as a paleoenvironmental stress proxy, but rare, naturally trisaccate lineages are not suitable for such assessments. Furthermore, heightened UV-B not only increases pollen malformation production, but also alters the types of abnormalities trees produce. Different environmental stresses may therefore leave behind distinct fingerprints in the fossil record.
Thyroid cancer and its associations with dietary quality in a 1:1 matched case–control study
Authors: Xia Manman , Zang Jiajie , Wang Zhengyuan , Wang Jiadong , Wu Yi , Liu Meixia , Shi Zehuan , Song Qi , Cui Xueying , Jia Xiaodong , Wu Fan
Published: April 2022

Thyroid cancer (TC) incidence has increased greatly during the past decades with a few established risk factors, while no study is available that has assessed the association of the Chinese Health Dietary Index (CHDI) with TC. We conducted a 1:1 matched case–control study in two hospitals in Shanghai, China. Diet-quality scores were calculated according to CHDI using a validated and reliable FFQ. Conditional logistic regression analysis and restricted cubic spline analysis were used to reveal potential associations between CHDI score and TC risk. A total of 414 pairs of historically confirmed TC patients and healthy controls were recruited from November 2012 to December 2015. The total score of cases and controls were 67·5 and 72·8, respectively (P < 0·001). The median score of total vegetables, fruit, diary products, dark green and orange vegetables, fish, shellfish and mollusk, soyabean, whole grains, dry bean and tuber in cases was significantly lower than those in controls. Compared with the reference group (≤60 points), the average (60–80 points) and high (≥80 points) levels of the CHDI score were associated with a reduced risk of TC (OR: 0·40, 95 % CI 0·26, 0·63 for 60–80 points; OR: 0·22, 95 % CI 0·12, 0·38 for ≥80 points). In age-stratiﬁed analyses, the favourable association remained signiﬁcant among participants who are younger than 50 years old. Our data suggested that high diet quality as determined by CHDI was associated with lower risk of TC.
Alcohol consumption and lower risk of cardiovascular and all-cause mortality: the impact of accounting for familial factors in twins
Authors: Ystrom Eivind , Degerud Eirik , Tesli Martin , Høye Anne , Reichborn-Kjennerud Ted , Næss Øyvind
Published: April 2022

Background

A moderate to high alcohol consumption is associated with a lower risk of cardiovascular disease (CVD) mortality in comparison with low consumption. The mechanisms underlying this association are not clear and have been suggested to be caused by residual confounding. The main objective of this study was to separate the familial and individual risk for CVD mortality and all-cause mortality related to alcohol consumption. This will be done by estimating the risk for CVD mortality and all-cause mortality in twin pairs discordant for alcohol consumption.

Methods

Alcohol consumption was assessed at two time points using self-report questionnaires in the Norwegian Twin Registry. Data on CVD mortality was obtained from the Norwegian Cause of Death Registry. Exposure–outcome associations for all-cause mortality and mortality due to other causes than CVD were estimated for comparison.

Results

Coming from a family with moderate to high alcohol consumption was protective against cardiovascular death (HR = 0.54, 95% CI 0.65–0.83). Moderate and high alcohol consumption levels were associated with a slightly increased risk of CVD mortality at the individual level (HR = 1.33, 95% CI 1.02–1.73). There was no association between alcohol consumption and all-cause mortality both at the familial nor at the individual level.

Conclusions

The protective association of moderate to high alcohol consumption with a lower risk of CVD mortality was accounted for by familial factors in this study of twins. Early life genetic and environmental familial factors may mask an absence of health effect of moderate to high alcohol consumption on cardiovascular mortality.
Longitudinal study of SARS-CoV-2 infections in different employee groups of long distance train services from June 2020 until February 2021 in Germany
Authors: Kim HyoungJin , Schultz-Heienbrok Robert , Uhle Markus , Neubert Jenni , Ball Fabian , Metz Matthes , Gravert Christian
Published: April 2022

This prospective longitudinal epidemiological study was aimed at investigating the occupational SARS-CoV-2 infection risk of long distance train services in Germany. Three different employee groups (train attendants, train drivers and maintenance workers) within the workforce of the German railway carrier Deutsche Bahn Fernverkehr AG were studied based on their contact frequency with passengers and colleagues. Approximately 1100 employees were tested by PCR for acute infections and by antibody detection for past infections in June 2020, October 2020 and February 2021. Cumulative incidence (acute and past infections) after the third (final) test series in February 2021 was 8.5% (95% interval CI 6.8–10.4): 8.5% (95% CI 6.2–11.2) for train attendants, 5.5% (95% CI 2.9–9.5) for train drivers and 11.8% (95% CI 7.6–17.2) for maintenance workers. Between June 2020 and October 2020, the incidence was 1.2% (95% CI 0.6–2.3): 1.2% (95% CI 0.4–2.7) for train attendants, 1.1% (95% CI 0.1–3.9) for train drivers and 1.4% (95% CI 0.17–5.10) for maintenance workers. Between October 2020 and February 2021, it was 5.1% (95% CI 3.6–6.8): 5.2% (95% CI 3.3–7.8) for train attendants, 1.6% (95% CI 0.3–4.5) for train drivers and 8.8% (95% CI 4.9–14.3) for maintenance workers. Thus, contrary to expectation our exploratory data did not show train attendants to be at the highest risk of SARS-CoV-2 infections among the employee groups. In line with expectations, train drivers, representing the low contact group, seemed at lowest occupational risk.
Developmental pathways from preschool temper tantrums to later psychopathology
Authors: Hoyniak Caroline P. , Donohue Meghan R. , Quiñones-Camacho Laura E. , Vogel Alecia C. , Perino Michael T. , Hennefield Laura , Tillman Rebecca , Barch Deanna M. , Luby Joan L.
Published: April 2022

Temper tantrums are sudden, overt negative emotional displays that are disproportionate to the eliciting event. Research supports that severe temper tantrums during the preschool period are associated with preschool psychopathology, but few studies have identified which characteristics of preschool tantrums are predictive of distal psychopathological outcomes in later childhood and adolescence. To examine this question, we used a prospective, longitudinal dataset enriched for early psychopathology. Participants (N = 299) included 3-to 6-year-old children (47.8% female) assessed for tantrums and early childhood psychopathology using diagnostic interviews and then continually assessed using diagnostic interviews over 10 subsequent time points throughout childhood and adolescence. We identified two unique groupings of tantrum behaviors: aggression towards others/objects (e.g., hitting others) and aggression towards self (e.g., hitting self). While both types of tantrum behaviors were associated with early childhood psychopathology severity, tantrum behaviors characterized by aggression towards self were more predictive of later psychopathology. Children displaying high levels of both types of tantrum behaviors had more severe externalizing problems during early childhood and more severe depression and oppositional defiant disorder across childhood and adolescence. Findings suggest that tantrum behaviors characterized by aggression towards self are particularly predictive of later psychopathology.
Heterogeneous trajectories of suicidal ideation among homeless youth: predictors and suicide-related outcomes
Authors: Wu Qiong , Zhang Jing , Walsh Laura , Slesnick Natasha
Published: April 2022

The current study examined heterogeneous trajectories of suicidal ideation among homeless youth experiencing suicidal ideation over 9 months in a randomized controlled intervention study. Suicidal homeless youth (N= 150) were randomly assigned to Cognitive Therapy for Suicide Prevention (CTSP) + Treatment as Usual (TAU) or TAU alone. Youth reported their suicidal ideation four times during a 9-month period. We also assessed pretreatment mental health, demographic information and session attendance as predictors of the subgroups, as well as suicide-related factors as outcomes at the 9-month follow-up. Growth mixture models suggested three distinct trajectory groups among youth: Fast Declining (74.7%), Chronic (19.3%), and Steadily Declining (6.0%). Youth in the Chronic group used more substances at baseline than the Steadily Declining group, were more likely to be White, non-Hispanic than the Fast Declining group, and attended more CTSP sessions than other groups. Contrastingly, youth in the Steadily Declining group all experienced childhood abuse. Finally, youth in the Chronic group showed significant higher risk for future suicide compared to those in the Fast Declining group at 9 months. Findings support the heterogeneity of treatment responses in suicide intervention among homeless youth, with implications to improve treatment efforts in this very high-risk population.
On Laws of Politics and How to Establish Them
Authors: Weber Erik
Published: April 2022

Alfred Cuzán proposed five “laws of politics” that allegedly govern elections in democracies. Drawing from insights in the general philosophy of science and the philosophy of the social sciences, I argue that—although his empirical evidence is impressive—he failed to develop a convincing argument for calling the five theses “laws.” This article discusses other examples that often are claimed to be “laws of politics” and describes the global picture supporting this analysis.
Beeinflusst das orale Mikrobiom kanzerogene Veränderungen des Ösophagus?
Authors: Groß Ralph Wolfgang , Schmieder Eileen , Fetzner Ulrich Klaus , Kleinert Robert , Nisi Antonio , Saely Christoph
Published: April 2022

Zusammenfassung. Das orale Mikrobiom spielt eine entscheidende Rolle bei der Aufrechterhaltung eines physiologischen oralen und ösophagealen Milieus, möglicherweise aber auch bei Entstehung und Progression von Erkrankungen, wie beispielsweise dem Ösophaguskarzinom. Der zugrundeliegende Mechanismus für diese Korrelation ist aber nicht geklärt. Ösophaguskarzinome bergen eine hohe Malignität und zeigen eine hohe Inzidenz – weltweit sind sie die sechsthäufigste karzinombedingte Todesursache. Ziel der Studie war es, herauszufinden inwieweit das orale Mikrobiom als Marker zur Früherkennung von Ösophaguskrebs herangezogen werden kann. Eine systematische Literaturrecherche wurde in den Datenbanken Pubmed®, Livivo® und Cochrane Library® durchgeführt. Insgesamt konnten acht Studien in das Review aufgenommen werden. Diese zeigen eine Korrelation zwischen oraler Dysbiose und erhöhtem Ösophaguskarzinom-Risiko, das heisst eine erhöhte (darunter Gattungen Prevotella, Porphyromonas, Streptococcus) oder verringerte (darunter Gattungen Haemophilus, Neisseria) relative Häufigkeit verschiedener Bakterien war mit einem höheren Risiko assoziiert. Die Resultate der Studien waren jedoch sehr heterogen. Es zeigt sich eine Korrelation zwischen karzinogenen Veränderungen des Ösophagus und Veränderungen im oralen Mikrobiom. Weitere Untersuchungen sind jedoch erforderlich, um eine mögliche kausale Rolle der oralen Mikrobiota bei der Karzinogenese zu klären.
Air‐Sea Interactions and Water Mass Transformation During a Katabatic Storm in the Irminger Sea
Authors: Gutjahr O. , Jungclaus J. H. , Brüggemann N. , Haak H. , Marotzke J.
Published: April 2022

We use a global 5‐km resolution model to analyze the air‐sea interactions during a katabatic storm in the Irminger Sea originating from the Ammassalik valleys. Katabatic storms have not yet been resolved in global climate models, raising the question of whether and how they modify water masses in the Irminger Sea. Our results show that dense water forms along the boundary current and on the shelf during the katabatic storm due to the heat loss caused by the high wind speeds and the strong temperature contrast. The dense water contributes to the lightest upper North Atlantic Deep Water as upper Irminger Sea Intermediate Water and thus to the lower limb of the Atlantic Meridional Overturning Circulation (AMOC). The katabatic storm triggers a polar low, which in turn amplifies the near‐surface wind speed due to the superimposed pressure gradient, in addition to acceleration from a breaking mountain wave. Overall, katabatic storms account for up to 25% of the total heat loss (20 January 2020 to 30 September 2021) over the Irminger shelf of the Ammassalik area. Resolving katabatic storms in global models is therefore important for the formation of dense water in the western boundary current of the Irminger Sea, which is relevant to the AMOC, and for the large‐scale atmospheric circulation by triggering polar lows.
Investigation of Wave Height Distributions and Characteristic Wave Periods in Coastal Environments
Authors: James Jemerson P. , Panchang Vijay
Published: April 2022

The short‐term statistics of wave conditions in coastal waters around the United Kingdom have been investigated using over 40,000 half‐hour long sea state records with significant wave height greater than 3 m. The extensive data set facilitates an assessment of various wave height and period distribution models in shallow and intermediate waters. The results reveal that the relative wave height Hs/D (where Hs is the significant wave height and D the water depth) can serve as a key indicator in choosing the distribution with least error in a given sea state. The Naess model is found to be the most accurate in describing the tail of the wave height distribution in a sea state for low relative wave heights (Hs/D < 0.2), and the depth‐dependent van Vledder model for high relative heights (Hs/D > 0.4). In between these sea states, a transition in the performance of the deep‐water and the depth‐dependent models is visible. When details of the spectrum are not available, the Weibull distribution is the most accurate amongst applicable models, in spite of considerable variability in its parameter values. While the spectral bandwidth appears to have minimal impact on the distribution of wave heights in a sea state, it does appear to influence the relationship between characteristic wave periods. Based on measurements, these are found to deviate from empirical relationships proposed, for example, by the US Army Coastal Engineering Manual. Improved formulas that incorporate the spectral width are therefore proposed.
Tracking the Space‐Time Evolution of Ocean Acidification Extremes in the California Current System and Northeast Pacific
Authors: Desmet Flora , Gruber Nicolas , Köhn Eike E. , Münnich Matthias , Vogt Meike
Published: April 2022

Ocean acidification is punctuated by episodic extremes of low pH and saturation state with regard to aragonite (ΩA). Here, we use a hindcast simulation from 1984 to 2019 with a high‐resolution regional ocean model (ROMS‐BEC) to identify and track ocean acidification extremes (OAX) in the northeast Pacific and the California current system (CCS). In the first step, we identify all grid‐cells whose pH and ΩA are simultaneously below their first percentile over the analysis period (1984–2019). In the second step, we aggregate all neighboring cells with extreme conditions into three‐dimensional time evolving events, permitting us to track them in a Lagrangian manner over their lifetime. We detect more than 22 thousand events that occur at least once in the upper 100 m during their lifetime, with broad distributions in terms of size, duration, volume, and intensity, and with 26% of them harboring corrosive conditions (ΩA < 1). By clustering the OAXs, we find three types of extremes in the CCS. Near the coast, intense, shallow, and short‐lasting OAXs dominate, caused by strong upwelling. A second type consists of large and long‐lasting OAX events that are associated with westward propagating cyclonic eddies. They account for only 3% of all extremes, but are the most severe events. The third type is small extremes at depth arising from pycnocline heave. OAXs potentially have deleterious effects on marine life. Marine calcifiers, such as pteropods, might be especially impacted by the long‐lasting events with corrosive conditions.
Rapid Characterization of Large Volcanic Eruptions: Measuring the Impulse of the Hunga Tonga Ha’apai Explosion From Teleseismic Waves
Authors: Poli Piero , Shapiro Nikolai M.
Published: April 2022

Most of the largest volcanic activity in the world occurs in remote places such as deep oceans or poorly monitored oceanic island arcs. Thus, our capacity of monitoring volcanoes is limited to remote sensing and global geophysical observations. However, the rapid estimation of volcanic eruption parameters is needed for scientific understanding of the eruptive process and rapid hazard estimation. We present a method to rapidly identify large volcanic explosions, based on analysis of seismic data. With this methodology, we promptly detect the 15 January 2022 Hunga Tonga Ha’apai eruption. We then analyze the seismic waves generated by the volcanic explosion and estimate its important first‐order parameters. We further relate the parameters with the volcanic explosivity index (VEI). Our estimate of VEI ∼ 6 indicates that how the Hunga Tonga eruption is among the largest volcanic activity ever recorded with modern geophysical instrumentation and can provide new insights into the physics of large eruptions.
How a faecal immunochemical test screening programme changes annual colorectal cancer incidence rates: an Italian intention-to-screen study
Authors: Bucchi Lauro , Mancini Silvia , Baldacchini Flavia , Ravaioli Alessandra , Giuliani Orietta , Vattiato Rosa , Zamagni Federica , Giorgi Rossi Paolo , Campari Cinzia , Canuti Debora , Di Felice Enza , Sassoli de Bianchi Priscilla , Ferretti Stefano , Bertozzi Nicoletta , Biggeri Annibale , Falcini Fabio ,   the Emilia-Romagna Region Workgroup for Colorectal Screening Evaluation, Di Felice Enza , Finarelli Alba Carola , Landi Patrizia , Naldoni Carlo , Sassoli de Bianchi Priscilla , Colamartini Americo , Borciani Elisabetta , Fornari Fabio , Gatti Giorgio , Pennini Francesca , Seghini Pietro , Dalla Fiora Cristian , Fattibene Claudio , Maradini Fabio , Michiara Maria , Orsi Paolo , Zurlini Corrado , Mangone Lucia , Paterlini Luisa , Sassatelli Romano , Carrozzi Giuliano , Corradini Rossella , Rossi Federica , Trande Paolo , Viani Simona , Bazzani Carmen , Bazzoli Franco , Cennamo Vincenzo , Giansante Chiara , Gualandi Giovanna , Manfredi Marilena , Mezzetti Francesca , Pasquini Adriana , Caprara Licia , De Lillo Margherita , Nannini Roberto , Carpanelli Maria Cristina , De Togni Aldo , Matarese Vincenzo , Palmonari Caterina , Pasquali Daniela , Zoli Giorgio , Dal Re Serena , Petrini Chiara , Serafini Monica , Vitali Benedetta , Gallinucci Mara , Imolesi Claudia , Palazzi Mauro , Ricci Enrico , Severi Mirna , Casale Coralba , Giovanardi Mauro , Trombetti Daniele
Published: April 2022

Background

This study aimed to evaluate the effectiveness of a biennial faecal immunochemical test (FIT) screening programme in reducing annual colorectal cancer (CRC) incidence in its dynamic target population.

Methods

The target population included over 1,000,000 persons aged 50–69 living in a region of northern Italy. The average annual response rate to invitation was 51.4%. Each observed annual age-standardised (Europe) rate per 100,000 persons between 2005, the year of introduction of the programme, and 2016 was compared with each expected annual rate as estimated with age-period-cohort (men) and age-period (women) models.

Results

For both sexes, the rates observed in 1997–2004 and those expected in 2005–2016 were stable. Observed rates increased in 2005, peaked in 2006 (the first full year of screening), dropped significantly below the expected level in 2009, and continued to decrease until 2013 (the eighth full year), after which no further significant changes occurred. In the pooled years 2013–2016, the observed incidence rate per 100,000 persons was 102.2 [95% CI: 97.4, 107.1] for men, 75.6 [95% CI: 71.6, 79.7] for women and 88.4 [95% CI: 85.3, 91.5] for both sexes combined, with an observed:expected incidence rate ratio of 0.68 [95% CI: 0.65, 0.71], 0.79 [95% CI: 0.76, 0.82] and 0.72 [95% CI: 0.66, 0.81], respectively.

Discussion

The study provided multiple consistent proofs of a causal relationship between the introduction of screening and a stable 28% decrease in annual CRC incidence after eight years.
Exosomal miR-146a-5p and miR-155-5p promote CXCL12/CXCR7-induced metastasis of colorectal cancer by crosstalk with cancer-associated fibroblasts
Authors: Wang Dong , Wang Xiaohui , Song Yujia , Si Mahan , Sun Yuqi , Liu Xiaohui , Cui Shuxiang , Qu Xianjun , Yu Xinfeng
Published: April 2022

C-X-C motif chemokine receptor 7 (CXCR7) is a newly discovered atypical chemokine receptor that binds to C-X-C motif chemokine ligand 12 (CXCL12) with higher affinity than CXCR4 and is associated with the metastasis of colorectal cancer (CRC). Cancer-associated fibroblasts (CAFs) have been known to promote tumor progression. However, whether CAFs are involved in CXCR7-mediated metastasis of CRC remains elusive. We found a significant positive correlation between CXCR7 expression and CAF activation markers in colonic tissues from clinical specimens and in villin-CXCR7 transgenic mice. RNA sequencing revealed a coordinated increase in the levels of miR-146a-5p and miR-155-5p in CXCR7-overexpressing CRC cells and their exosomes. Importantly, these CRC cell-derived miR-146a-5p and miR-155-5p could be uptaken by CAFs via exosomes and promote the activation of CAFs through JAK2–STAT3/NF-κB signaling by targeting suppressor of cytokine signaling 1 (SOCS1) and zinc finger and BTB domain containing 2 (ZBTB2). Reciprocally, activated CAFs further potently enhanced the invasive capacity of CRC cells. Mechanistically, CAFs transfected with miR-146a-5p and miR-155-5p exhibited a robust increase in the levels of inflammatory cytokines interleukin-6, tumor necrosis factor-α, transforming growth factor-β, and CXCL12, which trigger the epithelial–mesenchymal transition and pro-metastatic switch of CRC cells. More importantly, the activation of CAFs by miR-146a-5p and miR-155-5p facilitated tumor formation and lung metastasis of CRC in vivo using tumor xenograft models. Our work provides novel insights into CXCR7-mediated CRC metastasis from tumor–stroma interaction and serum exosomal miR-146a-5p and miR-155-5p could serve as potential biomarkers and therapeutic targets for inhibiting CRC metastasis.
Stearoyl-CoA Desaturase inhibition reverses immune, synaptic and cognitive impairments in an Alzheimer’s disease mouse model
Authors: Hamilton Laura K. , Moquin-Beaudry Gaël , Mangahas Chenicka L. , Pratesi Federico , Aubin Myriam , Aumont Anne , Joppé Sandra E. , Légiot Alexandre , Vachon Annick , Plourde Mélanie , Mounier Catherine , Tétreault Martine , Fernandes Karl J. L.
Published: April 2022

The defining features of Alzheimer’s disease (AD) include alterations in protein aggregation, immunity, lipid metabolism, synapses, and learning and memory. Of these, lipid abnormalities are the least understood. Here, we investigate the role of Stearoyl-CoA desaturase (SCD), a crucial regulator of fatty acid desaturation, in AD pathogenesis. We show that inhibiting brain SCD activity for 1-month in the 3xTg mouse model of AD alters core AD-related transcriptomic pathways in the hippocampus, and that it concomitantly restores essential components of hippocampal function, including dendritic spines and structure, immediate-early gene expression, and learning and memory itself. Moreover, SCD inhibition dampens activation of microglia, key mediators of spine loss during AD and the main immune cells of the brain. These data reveal that brain fatty acid metabolism links AD genes to downstream immune, synaptic, and functional impairments, identifying SCD as a potential target for AD treatment.
Clinical-pathologic characteristics and response to neoadjuvant chemotherapy in triple-negative low Ki-67 proliferation (TNLP) breast cancers
Authors: Srivastava Pooja , Wang Tiannan , Clark Beth Z. , Yu Jing , Fine Jeffrey L. , Villatoro Tatiana M. , Carter Gloria J. , Brufsky Adam M. , Gorantla Vikram C. , Huggins-Puhalla Shannon L. , Emens Leisha A. , Basili Thais , da Silva Edaise M. , Reis-Filho Jorge S. , Bhargava Rohit
Published: April 2022

Triple-negative breast cancers (TNBCs) often have a high Ki-67 proliferation index and respond favorably to neoadjuvant chemotherapy (NACT) with pathologic complete response (pCR) resulting in ~40% of cases. Nevertheless, morbidity/mortality remain high, mostly due to recurrence in patients with residual disease. In contrast, the incidence and clinical features of TNBC with low proliferation (TNLP), defined as TNBC with a Ki-67 index of ≤30% remains unknown. We report 70 cases of TNLP identified at our center from 2008 to 2018, including 18 treated with NACT. TNLP tumors represent <1% of all breast cancers, and ~5–10% of TNBCs. Ninety percent of carcinomas were grade I/II and 70% were either pure apocrine or showed apocrine differentiation. Fifty cases had available immunohistochemistry results; 80%, 84%, 22%, and 20% were positive for AR, INPP4B, nestin, and SOX10, respectively. With a median follow-up of 72 months, 14% experienced recurrence, and 11% died of breast cancer. The tumor stage was prognostic. Among 39 stage-I patients, 18 (46%) received chemotherapy, but this did not impact survival. There was a trend for improved recurrence-free survival with chemotherapy in stage-II patients. Of the 18 patients treated with NACT, 2 (11%) showed pCR; these were notable for either high stromal TILs or a high mitotic count despite a low Ki-67 index. TNLPs are enriched in low to intermediate-grade carcinomas with apocrine features. Due to overall good prognosis of stage-I TNLP and the lack of clear benefit of chemotherapy, de-escalation of chemotherapy may be considered in select patients with stage-I TNLP.
Granular cooling of ellipsoidal particles in microgravity
Authors: Pitikaris Sebastian , Bartz Patricia , Yu Peidong , Cristoforetti Samantha , Sperl Matthias
Published: April 2022

A three-dimensional granular gas of ellipsoids is established by exposing the system to the microgravity environment of the International Space Station. We use two methods to measure the dynamics of the constituent particles and report the long-time development of the granular temperature until no further particle movement is detectable. The resulting cooling behavior can be well described by Haff’s cooling law with time scale τ. Different analysis methods show evidence of particle clustering towards the end of the experiment. By using the kinetic theory for ellipsoids we compare the translational energy dissipation of individual collision events with the overall cooling time scale τ. The difference from this comparison indicates how energy is distributed in different degrees of freedom including both translation and rotation during the cooling.
Consumer purchase intention towards a quick response (QR) code for antibiotic information: an exploratory study
Authors: Bradford Hollie , McKernan Claire , Elliott Chris , Dean Moira
Published: April 2022

Increasing awareness of antimicrobial resistance (AMR) has raised concerns surrounding antimicrobial use (AMU) in food-producing animals and has focused attention towards livestock production free from antibiotic use. As antibiotic-free livestock production proliferates in the UK, there is an increasing need to implement a system, such as the use of a QR code, to provide consumers with reliable antibiotic information while ensuring that animal welfare standards are upheld. Subsequently, this study aims to explore UK consumers’ perceptions and purchase intention towards QR code labelled pork, and to identify determinants of its purchase, incorporating various theoretical constructs from the Theory of Planned Behaviour. Based on results, consumers’ perceptions, perceived control, and attitudes towards QR code labelled pork are the main determinants of purchase intention. QR code labelled pork may offer a suitable alternative to antibiotic-free labelling as it provides consumers with antibiotic information without inadvertently communicating that conventionally produced pork is unsafe.
CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition
Authors: Gallo David , Young Jordan T. F. , Fourtounis Jimmy , Martino Giovanni , Álvarez-Quilón Alejandro , Bernier Cynthia , Duffy Nicole M. , Papp Robert , Roulston Anne , Stocco Rino , Szychowski Janek , Veloso Artur , Alam Hunain , Baruah Prasamit S. , Fortin Alexanne Bonneau , Bowlan Julian , Chaudhary Natasha , Desjardins Jessica , Dietrich Evelyne , Fournier Sara , Fugère-Desjardins Chloe , Goullet de Rugy Theo , Leclaire Marie-Eve , Liu Bingcan , Bhaskaran Vivek , Mamane Yael , Melo Henrique , Nicolas Olivier , Singhania Akul , Szilard Rachel K. , Tkáč Ján , Yin Shou Yun , Morris Stephen J. , Zinda Michael , Marshall C. Gary , Durocher Daniel
Published: April 2022

Amplification of the CCNE1 locus on chromosome 19q12 is prevalent in multiple tumour types, particularly in high-grade serous ovarian cancer, uterine tumours and gastro-oesophageal cancers, where high cyclin E levels are associated with genome instability, whole-genome doubling and resistance to cytotoxic and targeted therapies1–4. To uncover therapeutic targets for tumours with CCNE1 amplification, we undertook genome-scale CRISPR–Cas9-based synthetic lethality screens in cellular models of CCNE1 amplification. Here we report that increasing CCNE1 dosage engenders a vulnerability to the inhibition of the PKMYT1 kinase, a negative regulator of CDK1. To inhibit PKMYT1, we developed RP-6306, an orally bioavailable and selective inhibitor that shows single-agent activity and durable tumour regressions when combined with gemcitabine in models of CCNE1 amplification. RP-6306 treatment causes unscheduled activation of CDK1 selectively in CCNE1-overexpressing cells, promoting early mitosis in cells undergoing DNA synthesis. CCNE1 overexpression disrupts CDK1 homeostasis at least in part through an early activation of the MMB–FOXM1 mitotic transcriptional program. We conclude that PKMYT1 inhibition is a promising therapeutic strategy for CCNE1-amplified cancers.
Mindfulness-based online intervention increases well-being and decreases stress after Covid-19 lockdown
Authors: Bossi Francesco , Zaninotto Francesca , D’Arcangelo Sonia , Lattanzi Nicola , Malizia Andrea P. , Ricciardi Emiliano
Published: April 2022

Mindfulness interventions were shown to be effective in improving well-being and reducing perceived stress in several conditions. These effects were also found in online mindfulness-based training, especially in employees in organizational environments. The aim of this study was to test the effectiveness of an online mindfulness intervention on healthy employees, especially after the first Italian Covid-19 lockdown. Participants in the intervention group underwent an 8-week mindfulness online training program based on the Mindfulness-Based Stress Reduction (MBSR) protocol compared to a control (no-intervention) group. All participants filled in weekly surveys for the whole intervention duration via online questionnaires to measure their habits, mindfulness (FFMQ-15), emotion regulation (ERQ), positive and negative affect (PANAS), depression, anxiety and stress (DASS-21), resilience (RSA) and insomnia (ISI). 69 participants in the intervention group and 63 in the no-treatment control group were considered in the longitudinal analyses. We found significant differences between the intervention and control groups over time in the measures of mindfulness (in particular the nonreactivity subscale), positive affect, depression, and insomnia. Moreover, we found that the frequency of practice and ease perceived in practicing were positively correlated to several indices of well-being (mindfulness, positive affect, cognitive reappraisal) and negatively correlated to several indices of stress (negative affect, depression, anxiety, stress, insomnia, expressive suppression). These results show the importance and effectiveness of online mindfulness training programs to cope with stress among employees, especially after the Covid-19 lockdown.
Development and validation of cost-effective one-step multiplex RT-PCR assay for detecting the SARS-CoV-2 infection using SYBR Green melting curve analysis
Authors: Sarkar Shovon Lal , Alam A. S. M. Rubayet Ul , Das Prosanto Kumar , Pramanik Md. Hasan Ali , Al-Emran Hassan M. , Jahid Iqbal Kabir , Hossain M. Anwar
Published: April 2022

TaqMan probe-based commercial real-time (RT) PCR kits are expensive but most frequently used in COVID-19 diagnosis. The unprecedented scale of SARS-CoV-2 infections needs to meet the challenge of testing more persons at a reasonable cost. This study developed a simple and cost-effective alternative diagnostic method based on melting curve analysis of SYBR green multiplex assay targeting two virus-specific genes along with a host-specific internal control. A total of 180 randomly selected samples portioning into two subsets based on crude and high-quality RNA extraction were used to compare this assay with a nationwide available commercial kit (Sansure Biotech Inc., (Hunan, China)), so that we could analyze the variation and validity of this in-house developed method. Our customized-designed primers can specifically detect the viral RNA likewise Sansure. We separately optimized SYBR Green RT-PCR reaction of N, E, S, and RdRp genes based on singleplex melting curve analysis at the initial stage. After several rounds of optimization on multiplex assays of different primer combinations, the optimized method finally targeted N and E genes of the SARS-CoV-2 virus, together with the β-actin gene of the host as an internal control. Comparing with the Sansure commercial kit, our proposed assay provided up to 97% specificity and 93% sensitivity. The cost of each sample processing ranged between ~2 and ~6 USD depending on the purification level of extracted RNA template. Overall, this one-step and one-tube method can revolutionize the COVID-19 diagnosis in low-income countries.
Effectiveness of emotional freedom techniques (EFT) vs sleep hygiene education group therapy (SHE) in management of sleep disorders among elderly
Authors: Souilm Nagwa , Elsakhy Nancy Mahmoud , Alotaibi Yasir A. , Ali Safaa Abdelazem Osman
Published: April 2022

Sleep disorders are common among elderly persons, with deleterious effects on their physical and mental health. Many approaches are used to manage such disorders. To compare the Emotional Freedom Techniques–Insomnia (EFT-I) and Sleep Hygiene Education (SHE) group therapy as two treatments for insomnia in a geriatric population when delivered, and their effects on sleep quality, depression, and life satisfaction. This open-label randomized controlled trial study was conducted at El-Abbasia Mental Hospital and Osana family wellness elderly nursing home at Maadi, Cairo. It included 60 elderly patients suffering insomnia sleep problems randomized into two equal groups: one group received a Sleep Hygiene Education (SHE) intervention, the other had a form of Emotional Freedom Techniques (EFT) adapted for use with insomnia (EFT-I). A self-administered questionnaire with tools for sleep quality (Pittsburgh Sleep Quality Index [PSQI]), depression, and life satisfaction was used to collect data. The fieldwork was from January to March 2021. The two groups had equal median age (70 years), and almost similar gender and place of residence distribution. After the intervention, 73.3% of the EFT group had good sleep quality, compared to 100.0% in the SHE group (P = 0.005); the median score of depression (3.00) was higher in the EFT group compared with 0.00 in the SHE group (P < 0.001); as for life satisfaction, the difference was not statistically significant. The multivariate analyses identified the study intervention as the main statistically significant negative predictor of PSQI and depression scores, and a positive predictor of life satisfaction. Being in the SHE group was a negative predictor of PSQI and depression scores. Both SHE and EFT approaches are beneficial for elderly patients’ sleep quality, with SHE being more effective in ameliorating sleep. Further replication of this study is needed on a large probability sample from different geographical areas to help for the generalization of the results.
Deep learning methodology for predicting time history of head angular kinematics from simulated crash videos
Authors: Hasija Vikas , Takhounts Erik G.
Published: April 2022

Head kinematics information is important as it is used to measure brain injury risk. Currently, head kinematics are measured using wearable devices or instrumentation mounted on the head. This paper evaluates the deep learning approach in predicting time history of head angular kinematics directly from videos without any instrumentation. To prove the concept, a deep learning model was developed for predicting time history of head angular velocities using finite element (FE) based crash simulation videos. This FE dataset was split into training, validation, and test datasets. A combined convolutional neural network and recurrent neural network based deep learning model was developed using the training and validations sets. The test (unseen) dataset was used to evaluate the predictive capability of the deep learning model. On the test dataset, correlation coefficient obtained between the actual and predicted peak angular velocities was 0.73, 0.85, and 0.92 for X, Y, and Z components respectively.
Predictors and predictive effects of acute pain trajectories after gastrointestinal surgery
Authors: Liu Qing-Ren , Dai Yu-Chen , Ji Mu-Huo , Qiu Li-Li , Liu Pan-Miao , Sun Xing-Bing , Yang Jian-Jun
Published: April 2022

Few studies have investigated factors associated with acute postsurgical pain (APSP) trajectories, and whether the APSP trajectory can predict chronic postsurgical pain (CPSP) remains unclear. We aimed to identify the predictors of APSP trajectories in patients undergoing gastrointestinal surgery. Moreover, we hypothesised that APSP trajectories were independently associated with CPSP. We conducted a prospective cohort study of 282 patients undergoing gastrointestinal surgery to describe APSP trajectories. Psychological questionnaires were administered 1 day before surgery. Meanwhile, demographic characteristics and perioperative data were collected. Average pain intensity during the first 7 days after surgery was assessed by a numeric rating scale (NRS). Persistent pain intensity was evaluated at 3 and 6 months postoperatively by phone call interview. CPSP was defined as pain at the incision site or surrounding areas of surgery with a pain NRS score ≥ 1 at rest. The intercept and slope were calculated by linear regression using the least squares method. The predictors for the APSP trajectory and CPSP were determined using multiple linear regression and multivariate logistic regression, respectively. Body mass index, morphine milligram equivalent (MME) consumption, preoperative chronic pain and anxiety were predictors of the APSP trajectory intercept. Moreover, MME consumption and preoperative anxiety could independently predict the APSP trajectory slope. The incidence of CPSP at 3 and 6 months was 30.58% and 16.42% respectively. APSP trajectory and age were predictors of CPSP 3 months postoperatively, while female sex and preoperative anxiety were predictive factors of CPSP 6 months postoperatively. Preoperative anxiety and postoperative analgesic consumption can predict APSP trajectory. In addition, pain trajectory was associated with CPSP. Clinicians need to stay alert for these predictors and pay close attention to pain resolution.
Comparing prognostic value of preoperative platelet indexes in patients with resectable gastric cancer
Authors: Shi Hongtai , Wang Hongsheng , Pan Jie , Liu Zhenhua , Li Zuoan
Published: April 2022

The ratio of mean platelet volume (MPV) to count (PC) (MPV/PC) has been applied in the diagnosis and prognosis of various malignancies. However, the prognostic value of MPV/PC in gastric cancer has not been studied yet. This study aims to explore the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), combined neutrophil-platelet score (CNPS), systemic immune-inflammation index (SII) and MPV/PC in patients with resectable gastric cancer. In this study, the medical records of patients with gastric cancer in two centers were retrospectively analyzed. Kaplan–Meier and log-rank were tests applied to analyze the survival differences of patients with various inflammation indexes. A nomogram prognostic model was established to predict the 3- and 5-year survival rate of patients with resectable gastric cancer. In the two cohorts, Kaplan–Meier analysis that the postoperative survival time of gastric cancer patients with low MPV/PC, high NLR, high PLR and high SII was significantly shorter than that of patients with high MPV/PC, low NLR, low PLR or low SII. Compared with NLR, PLR, SII and CNPS, MPV/PC was more accurate in determining the prognosis of patients with gastric cancer than other indexes, and multivariate analysis confirmed that MPV/PC was an independent prognostic factor for patients with resectable gastric cancer. The nomogram model established based on tumor size, TNM stage and MPV/PC was more accurate than TNM stage in predicting the 3- and 5-year survival rate of patients with resectable gastric cancer. Preoperative MPV/PC is a new independent prognostic index and a potential marker for treatment response monitoring in patients with resectable gastric cancer. The nomogram model for postoperative prognosis of gastric cancer established based on MPV/PC, tumor size and TNM stage is helpful for developing more accurate and timely individualized therapeutic regimens.
Harnessing the immunotherapeutic potential of CDK4/6 inhibitors in melanoma: is timing everything?
Authors: Lelliott Emily J. , Sheppard Karen E. , McArthur Grant A.
Published: April 2022

CDK4/6 inhibitors (CDK4/6i) were developed as a cancer therapeutic on the basis of their tumor-intrinsic cytostatic potential, but have since demonstrated profound activity as immunomodulatory agents. While currently approved to treat hormone receptor-positive breast cancer, these inhibitors are under investigation in clinical trials as treatments for a range of cancer types, including melanoma. Melanoma is a highly immunogenic cancer, and has always been situated at the forefront of cancer immunotherapy development. Recent revelations into the immunotherapeutic activity of CDK4/6i, therefore, have significant implications for the utility of these agents as melanoma therapies. In recent studies, we and others have proven the immunomodulatory effects of CDK4/6i to be multifaceted and complex. Among the most notable effects, CDK4/6 inhibition induces transcriptional reprogramming in both tumor cells and immune cells to enhance tumor cell immunogenicity, promote an immune-rich tumor microenvironment, and skew T cell differentiation into a stem-like phenotype that is more amenable to immune checkpoint inhibition. However, in some contexts, the specific immunomodulatory effects of CDK4/6i may impinge on anti-tumor immunity. For example, CDK4/6 inhibition restricts optimal T cells expansion, and when used in combination with BRAF/MEK-targeted therapies, depletes immune-potentiating myeloid subsets from the tumor microenvironment. We propose that such effects, both positive and negative, may be mitigated or exacerbated by altering the CDK4/6i dosing regimen. Here, we discuss what the most recent insights mean for clinical trial design, and propose clinical considerations and strategies that may exploit the full immunotherapeutic potential of CDK4/6 inhibitors.