bluuebunny/crossref_metadata_2025 huggingface dataset:
Segmental Versus Total Colectomy for Crohn’s Disease in the Biologic Era: Results From The SCOTCH International, Multicentric Study
Authors: Pellino Gianluca , Rottoli Matteo , Mineccia Michela , Frontali Alice , Celentano Valerio , Colombo Francesco , Baldi Caterina , Ardizzone Sandro , Martí Gallostra Marc , Espín-Basany Eloy , Ferrero Alessandro , Panis Yves , Poggioli Gilberto , Sampietro Gianluca M
Published: July 2022

Background

The extent of resection in colonic Crohn’s disease [cCD] is still a topic of debate, depending on the number of locations, the risk of recurrence and permanent stoma, and the role of medical therapy.

Methods

The Segmental COlecTomy for CroHn’s disease [SCOTCH] international study is a retrospective analysis on six tertiary centre prospective databases, comprising all consecutive, unselected patients operated on between 2000 and 2019 with segmental colectomy [SC] or total colectomy [TC] for cCD. The primary aim was long-term surgical recurrence. Secondary aims were perioperative complications, stoma formation and predictors of recurrence.

Results

Among 687 patients, SC was performed in 285 [41.5%] and TC in 402 [58.5%]. Mean age at diagnosis and surgery, disease duration, and follow-up were 30 ± 15.8, 40.4 ± 15.4, 10.4 ± 8.6 and 7.1 ± 5.2 years respectively. Isolated cCD, inflammatory pattern, perianal CD, younger age, longer disease duration and preoperative maximal therapy were more frequent in TC, while SC presented more small bowel locations and perforating disease, required fewer 90-day re-admissions, and fewer temporary and definitive stomas. Morbidity and mortality were similar. The 15-year surgical recurrence was 44% in TC and 27% in SC [p = 0.006]. In patients with one to three diseased segments, recurrence risk was related to the omission of biological therapy (hazard ratio [HR] 5.6), the number of segments [HR 2.5], perianal disease [HR 1.9] and paediatric diagnosis [HR 2.8].

Conclusion

When technically feasible, SC is safe and reduces temporary and permanent stoma. Young age, number of locations and perianal disease adversely affect, but postoperative biological therapy significantly reduces, the long-term surgical recurrence.
Falls prediction using the nursing home minimum dataset
Authors: Boyce Richard D , Kravchenko Olga V , Perera Subashan , Karp Jordan F , Kane-Gill Sandra L , Reynolds Charles F , Albert Steven M , Handler Steven M
Published: July 2022

Objective

The purpose of the study was to develop and validate a model to predict the risk of experiencing a fall for nursing home residents utilizing data that are electronically available at the more than 15 000 facilities in the United States.

Materials and Methods

The fall prediction model was built and tested using 2 extracts of data (2011 through 2013 and 2016 through 2018) from the Long-term Care Minimum Dataset (MDS) combined with drug data from 5 skilled nursing facilities. The model was created using a hybrid Classification and Regression Tree (CART)-logistic approach.

Results

The combined dataset consisted of 3985 residents with mean age of 77 years and 64% female. The model’s area under the ROC curve was 0.668 (95% confidence interval: 0.643–0.693) on the validation subsample of the merged data.

Discussion

Inspection of the model showed that antidepressant medications have a significant protective association where the resident has a fall history prior to admission, requires assistance to balance while walking, and some functional range of motion impairment in the lower body; even if the patient exhibits behavioral issues, unstable behaviors, and/or are exposed to multiple psychotropic drugs.

Conclusion

The novel hybrid CART-logit algorithm is an advance over the 22 fall risk assessment tools previously evaluated in the nursing home setting because it has a better performance characteristic for the fall prediction window of ≤90 days and it is the only model designed to use features that are easily obtainable at nearly every facility in the United States.
How Does Post-Earnings Announcement Sentiment Affect Firms’ Dynamics? New Evidence from Causal Machine Learning
Authors: Audrino Francesco , Chassot Jonathan , Huang Chen , Knaus Michael , Lechner Michael , Ortega Juan-Pablo
Published: July 2022

We revisit the role played by sentiment extracted from news articles related to earnings announcements as a driver of firms’ return, volatility, and trade volume dynamics. To this end, we apply causal machine learning on the earnings announcements of a wide cross-section of U.S. companies. This approach allows us to investigate firms’ price and volume reactions to different types of post-earnings announcement sentiment (positive, negative, and mixed sentiments) under various underlying macroeconomic, financial, and aggregated investors’ moods in a properly defined causal framework. Our empirical results support the presence of (i) economically sizable differences in the effects among sentiment types that are mostly of a non-linear nature depending on the underlying economic and financial conditions; (ii) a leverage effect in sentiment where reactions are (on average) larger for negative sentiment; and (iii) investors’ underreaction to news. In particular, we show that the difference in the average causal effects of the sentiment’s types is larger and more relevant when the general macroeconomic conditions are worse, the investors are pessimist about the behavior of the market and/or its uncertainty is higher, and in market regimes characterized by high stocks’ liquidity.
A Randomized Trial of Telephone-Based Smoking Cessation Treatment in the Lung Cancer Screening Setting
Authors: Taylor Kathryn L , Williams Randi M , Li Tengfei , Luta George , Smith Laney , Davis Kimberly M , Stanton Cassandra A , Niaura Raymond , Abrams David , Lobo Tania , Mandelblatt Jeanne , Jayasekera Jinani , Meza Rafael , Jeon Jihyoun , Cao Pianpian , Anderson Eric D ,   the Georgetown Lung Screening, Tobacco, and Health Trial
Published: July 2022

Background

Lung cancer mortality is reduced via low-dose computed tomography screening and treatment of early-stage disease. Evidence-based smoking cessation treatment in the lung screening setting can further reduce mortality. We report the results of a cessation trial from the National Cancer Institute’s Smoking Cessation at Lung Examination collaboration.

Methods

Eligible patients (n = 818) aged 50-80 years were randomly assigned (May 2017-January 2021) to the intensive vs minimal arms (8 vs 3 phone sessions plus 8 vs 2 weeks of nicotine patches, respectively). Bio-verified (primary) and self-reported 7-day abstinence rates were assessed at 3, 6, and 12 months post random assignment. Logistic regression analyses evaluated the effects of study arm. All statistical tests were 2-sided.

Results

Participants reported 48.0 (SD = 17.2) pack-years, and 51.6% were not ready to quit in less than 30 days. Self-reported 3-month quit rates were statistically significantly higher in the intensive vs minimal arm (14.3% vs 7.9%; odds ratio [OR] = 2.00, 95% confidence interval [CI] = 1.26 to 3.18). Bio-verified abstinence was lower but with similar relative differences between arms (9.1% vs 3.9%; OR = 2.70, 95% CI = 1.44 to 5.08). Compared with the minimal arm, the intensive arm was more effective among those with greater nicotine dependence (OR = 3.47, 95% CI = 1.55 to 7.76), normal screening results (OR = 2.58, 95% CI = 1.32 to 5.03), high engagement in counseling (OR = 3.03, 95% CI = 1.50 to 6.14), and patch use (OR = 2.81, 95% CI = 1.39 to 5.68). Abstinence rates did not differ statistically significantly between arms at 6 months (OR = 1.2, 95% CI = 0.68 to 2.11) or 12 months (OR = 1.4, 95% CI = 0.82 to 2.42).

Conclusions

Delivering intensive telephone counseling and nicotine replacement with lung screening is an effective strategy to increase short-term smoking cessation. Methods to maintain short-term effects are needed. Even with modest quit rates, integrating cessation treatment into lung screening programs may have a large impact on tobacco-related mortality.
SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19
Authors: Serrano Geidy E , Walker Jessica E , Tremblay Cécilia , Piras Ignazio S , Huentelman Matthew J , Belden Christine M , Goldfarb Danielle , Shprecher David , Atri Alireza , Adler Charles H , Shill Holly A , Driver-Dunckley Erika , Mehta Shyamal H , Caselli Richard , Woodruff Bryan K , Haarer Chadwick F , Ruhlen Thomas , Torres Maria , Nguyen Steve , Schmitt Dasan , Rapscak Steven Z , Bime Christian , Peters Joseph L , Alevritis Ellie , Arce Richard A , Glass Michael J , Vargas Daisy , Sue Lucia I , Intorcia Anthony J , Nelson Courtney M , Oliver Javon , Russell Aryck , Suszczewicz Katsuko E , Borja Claryssa I , Cline Madison P , Hemmingsen Spencer J , Qiji Sanaria , Hobgood Holly M , Mizgerd Joseph P , Sahoo Malaya K , Zhang Haiyu , Solis Daniel , Montine Thomas J , Berry Gerald J , Reiman Eric M , Röltgen Katharina , Boyd Scott D , Pinsky Benjamin A , Zehnder James L , Talbot Pierre , Desforges Marc , DeTure Michael , Dickson Dennis W , Beach Thomas G
Published: July 2022

Brains of 42 COVID-19 decedents and 107 non-COVID-19 controls were studied. RT-PCR screening of 16 regions from 20 COVID-19 autopsies found SARS-CoV-2 E gene viral sequences in 7 regions (2.5% of 320 samples), concentrated in 4/20 subjects (20%). Additional screening of olfactory bulb (OB), amygdala (AMY) and entorhinal area for E, N1, N2, RNA-dependent RNA polymerase, and S gene sequences detected one or more of these in OB in 8/21 subjects (38%). It is uncertain whether these RNA sequences represent viable virus. Significant histopathology was limited to 2/42 cases (4.8%), one with a large acute cerebral infarct and one with hemorrhagic encephalitis. Case-control RNAseq in OB and AMY found more than 5000 and 700 differentially expressed genes, respectively, unrelated to RT-PCR results; these involved immune response, neuronal constituents, and olfactory/taste receptor genes. Olfactory marker protein-1 reduction indicated COVID-19-related loss of OB olfactory mucosa afferents. Iba-1-immunoreactive microglia had reduced area fractions in cerebellar cortex and AMY, and cytokine arrays showed generalized downregulation in AMY and upregulation in blood serum in COVID-19 cases. Although OB is a major brain portal for SARS-CoV-2, COVID-19 brain changes are more likely due to blood-borne immune mediators and trans-synaptic gene expression changes arising from OB deafferentation.
Clinical application and accuracy assessment of imaging-based surgical navigation guided 125I interstitial brachytherapy in deep head and neck regions
Authors: Zhang Guohao , Wu Zhiyuan , Yu Wenting , Lyu Xiaoming , Wu Wenjie , Fan Yi , Wang Yong , Zheng Lei , Huang Mingwei , Zhang Yi , Guo Chuanbin , Zhang Jianguo
Published: July 2022

Brachytherapy has the advantages of being minimally invasive and highly conformal, and it achieves good results in head and neck tumors. To precisely implant the radioactive seeds according to the preplan in deep head and neck regions, the surgical navigation is applied. This study aims to explore the clinical application and accuracy of imaging-based surgical navigation-guided 125I interstitial brachytherapy in terms of seed position. We included 41 patients with tumors in deep head and neck regions. The brachytherapy treatment plan was designed, and the preplanned data were transferred to the navigation system. Needle implantation and seed delivery were performed under surgical navigation system guidance with or without the combination of individual template. The treatment accuracy was evaluated by comparing seed cluster locations between the preoperative treatment plan and the postoperative treatment outcome. A total of 2879 seeds were delivered. The range, mean and median distances between the geometric centers of the preoperative seed point clusters and the postoperative seed point clusters were 0.8–10.5 mm, 4.5 ± 2.3 mm and 4.1 mm, respectively. The differences between preoperative and postoperative volumes of the minimum bounding box of seed point clusters were nonsignificant. In conclusion, the imaging-based surgical navigation system is a promising clinical tool to provide the preplanned data for interstitial brachytherapy intraoperatively, and it is feasible and accurate for the real-time guidance of needle implantation and seed delivery in deep head and neck regions.
Potential inhibitory effects of low-dose thoron inhalation and ascorbic acid administration on alcohol-induced hepatopathy in mice
Authors: Kataoka Takahiro , Ishida Tsuyoshi , Naoe Shota , Kanzaki Norie , Sakoda Akihiro , Tanaka Hiroshi , Mitsunobu Fumihiro , Yamaoka Kiyonori
Published: July 2022

Although thoron inhalation exerts antioxidative effects in several organs, there are no reports on whether it inhibits oxidative stress-induced damage. In this study, we examined the combined effects of thoron inhalation and ascorbic acid (AA) administration on alcohol-induced liver damage. Mice were subjected to thoron inhalation at 500 or 2000 Bq/m3 and were administered 50% ethanol (alcohol) and 300 mg/kg AA. Results showed that although alcohol administration increased the levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) in the serum, the combination of thoron inhalation (500 Bq/m3) and AA administration 24 h after alcohol administration effectively inhibited alcohol-induced liver damage. The combination of thoron inhalation (500 Bq/m3) and AA administration 24 h after alcohol administration increased catalase (CAT) activity. Alcohol administration significantly decreased glutathione (GSH) levels in the liver. The GSH content in the liver after 2000 Bq/m3 thoron inhalation was lower than that after 500 Bq/m3 thoron inhalation. These findings suggest that the combination of thoron inhalation at 500 Bq/m3 and AA administration has positive effects on the recovery from alcohol-induced liver damage. The results also suggested that thoron inhalation at 500 Bq/m3 was more effective than that at 2000 Bq/m3, possibly because of the decrease in GSH content in the liver. In conclusion, the combination of thoron inhalation at 500 Bq/m3 and AA administration promoted an early recovery from alcohol-induced liver damage.
Earth through the looking glass: how frequently are we detected by other civilizations through photometric microlensing?
Authors: Suphapolthaworn S , Awiphan S , Chatchadanoraset T , Kerins E , Specht D , Nakharutai N , Komonjinda S , Robin A C
Published: July 2022

Microlensing is proving to be one of the best techniques to detect distant, low-mass planets around the most common stars in the Galaxy. In principle, Earth’s microlensing signal could offer the chance for other technological civilizations to find the Earth across Galactic distances. We consider the photometric microlensing signal of Earth to other potential technological civilizations and dub the regions of our Galaxy from which Earth’s photometric microlensing signal is most readily observable as the ‘Earth microlensing zone’ (EMZ). The EMZ can be thought of as the microlensing analogue of the Earth Transit Zone (ETZ) from where observers see Earth transit the Sun. Just as for the ETZ, the EMZ could represent a game-theoretic Schelling point for targeted searches for extra-terrestrial intelligence (SETI). To compute the EMZ, we use the Gaia DR2 catalogue with magnitude G < 20 to generate Earth microlensing probability and detection rate maps to other observers. While our Solar system is a multiplanet system, we show that Earth’s photometric microlensing signature is almost always well approximated by a binary lens assumption. We then show that the Earth is in fact well hidden to observers with technology comparable to our own. Specifically, even if observers are located around every Gaia DR2 star with G < 20, we expect photometric microlensing signatures from the Earth to be observable on average only tens per year by any of them. In addition, the EMZs overlap with the ETZ near the Galactic Centres which could be the main areas for future SETI searches.
Modelling of multimode radially pulsating high-amplitude δ Scuti stars from the OGLE Galactic bulge sample
Authors: Netzel H , Smolec R
Published: July 2022

Thanks to relatively firm mode identification, possible based only on period ratios, high-amplitude δ Scuti stars pulsating in at least three radial modes are promising targets for asteroseismic inference. In this study, we used the most numerous sample of HADS from the OGLE inner bulge fields that likely pulsate in either three or four radial modes simultaneously. We have computed a grid of pulsation models along evolutionary tracks and determined the physical parameters of stars by matching their pulsation periods and period ratios. For 176 HADS, we determined physical parameters, i.e. masses, luminosities, effective temperatures, metallicities, and ages. We present the distribution of physical parameters and discuss their properties. We selected 16 candidates for SX Phoenicis stars.
Investigation of rocket effect in bright-rimmed clouds using Gaia EDR3
Authors: Saha Piyali , Maheswar G , Ojha D K , Baug Tapas , Neha Sharma
Published: July 2022

Bright-rimmed clouds (BRCs) are excellent laboratories to explore the radiation-driven implosion mode of star formation because they show evidence of triggered star formation. In our previous study, BRC 18 has been found to accelerate away from the direction of the ionizing H ii region because of the well-known ‘Rocket Effect’. Based on the assumption that both BRC 18 and the candidate young stellar objects (YSOs) are kinematically coupled and using the latest Gaia EDR3 measurements, we found that the relative proper motions of the candidate YSOs exhibit a tendency of moving away from the ionizing source. Using BRC 18 as a prototype, we made our further analysis for 21 more BRCs, a majority of which showed a similar trend. For most of the BRCs, the median angle of the relative proper motion of the candidate YSOs is similar to the angle of on-sky direction from the ionizing source to the central IRAS source of the BRC. Based on the Pearson’s and Spearman’s correlation coefficients, we found a strong correlation between these two angles, which is further supported by the Kolmogorov–Smirnov (K−S) test on them. The strong correlation between these two angles supports the ‘Rocket Effect’ in the BRCs on the sky plane.
The quintessence of metallomics: a harbinger of a different life science based on the periodic table of the bioelements
Authors: Maret Wolfgang
Published: July 2022

This year marks the 20th anniversary of the field of metallomics. As a landmark in time, it is an occasion to reflect on the past, present, and future of this integrated field of biometal sciences. A fundamental bias is one reason for having metallomics as a scientific discipline. The focus of biochemistry on the six non-metal chemical elements, collectively known with the acronym SPONCH (sulphur, phosphorus, oxygen, nitrogen, carbon, hydrogen), glosses over the fact that the lower quantities of many other elements have qualities that made them instrumental in the evolution of life and pivotal in numerous life processes. The metallome, alongside the genome, proteome, lipidome, and glycome, should be regarded as a fifth pillar of elemental—vis-à-vis molecular—building blocks in biochemistry. Metallomics as ‘global approaches to metals in the biosciences’ considers the biological significance of most chemical elements in the periodic table, not only the ones essential for life, but also the non-essential ones that are present in living matter—some at higher concentrations than the essential ones. The non-essential elements are bioactive with either positive or negative effects. Integrating the significance of many more chemical elements into the life sciences requires a transformation in learning and teaching with a focus on elemental biology in addition to molecular biology. It should include the dynamic interactions between the biosphere and the geosphere and how the human footprint is changing the ecology globally and exposing us to many additional chemical elements that become new bioelements.
Division of labor within the DNA damage tolerance system reveals non-epistatic and clinically actionable targets for precision cancer medicine
Authors: Spanjaard Aldo , Shah Ronak , de Groot Daniël , Buoninfante Olimpia Alessandra , Morris Ben , Lieftink Cor , Pritchard Colin , Zürcher Lisa M , Ormel Shirley , Catsman Joyce J I , de Korte-Grimmerink Renske , Siteur Bjørn , Proost Natalie , Boadum Terry , van de Ven Marieke , Song Ji-Ying , Kreft Maaike , van den Berk Paul C M , Beijersbergen Roderick L , Jacobs Heinz
Published: July 2022

Crosslink repair depends on the Fanconi anemia pathway and translesion synthesis polymerases that replicate over unhooked crosslinks. Translesion synthesis is regulated via ubiquitination of PCNA, and independently via translesion synthesis polymerase REV1. The division of labor between PCNA-ubiquitination and REV1 in interstrand crosslink repair is unclear. Inhibition of either of these pathways has been proposed as a strategy to increase cytotoxicity of platinating agents in cancer treatment. Here, we defined the importance of PCNA-ubiquitination and REV1 for DNA in mammalian ICL repair. In mice, loss of PCNA-ubiquitination, but not REV1, resulted in germ cell defects and hypersensitivity to cisplatin. Loss of PCNA-ubiquitination, but not REV1 sensitized mammalian cancer cell lines to cisplatin. We identify polymerase Kappa as essential in tolerating DNA damage-induced lesions, in particular cisplatin lesions. Polk-deficient tumors were controlled by cisplatin treatment and it significantly delayed tumor outgrowth and increased overall survival of tumor bearing mice. Our results indicate that PCNA-ubiquitination and REV1 play distinct roles in DNA damage tolerance. Moreover, our results highlight POLK as a critical TLS polymerase in tolerating multiple genotoxic lesions, including cisplatin lesions. The relative frequent loss of Polk in cancers indicates an exploitable vulnerability for precision cancer medicine.
De novoassembly of human genome at single-cell levels
Authors: Xie Haoling , Li Wen , Hu Yuqiong , Yang Cheng , Lu Jiansen , Guo Yuqing , Wen Lu , Tang Fuchou
Published: July 2022

Genome assembly has been benefited from long-read sequencing technologies with higher accuracy and higher continuity. However, most human genome assembly require large amount of DNAs from homogeneous cell lines without keeping cell heterogeneities, since cell heterogeneity could profoundly affect haplotype assembly results. Herein, using single-cell genome long-read sequencing technology (SMOOTH-seq), we have sequenced K562 and HG002 cells on PacBio HiFi and Oxford Nanopore Technologies (ONT) platforms and conducted de novo genome assembly. For the first time, we have completed the human genome assembly with high continuity (with NG50 of ∼2 Mb using 95 individual K562 cells) at single-cell levels, and explored the impact of different assemblers and sequencing strategies on genome assembly. With sequencing data from 30 diploid individual HG002 cells of relatively high genome coverage (average coverage ∼41.7%) on ONT platform, the NG50 can reach over 1.3 Mb. Furthermore, with the assembled genome from K562 single-cell dataset, more complete and accurate set of insertion events and complex structural variations could be identified. This study opened a new chapter on the practice of single-cell genome de novo assembly.
Structure of the human RAD17–RFC clamp loader and 9–1–1 checkpoint clamp bound to a dsDNA–ssDNA junction
Authors: Day Matthew , Oliver Antony W , Pearl Laurence H
Published: July 2022

The RAD9–RAD1–HUS1 (9–1–1) clamp forms one half of the DNA damage checkpoint system that signals the presence of substantial regions of single-stranded DNA arising from replication fork collapse or resection of DNA double strand breaks. Loaded at the 5′-recessed end of a dsDNA–ssDNA junction by the RAD17–RFC clamp loader complex, the phosphorylated C-terminal tail of the RAD9 subunit of 9–1–1 engages with the mediator scaffold TOPBP1 which in turn activates the ATR kinase, localised through the interaction of its constitutive partner ATRIP with RPA-coated ssDNA. Using cryogenic electron microscopy (cryoEM) we have determined the structure of a complex of the human RAD17–RFC clamp loader bound to human 9–1–1, engaged with a dsDNA–ssDNA junction. The structure answers the key questions of how RAD17 confers specificity for 9–1–1 over PCNA, and how the clamp loader specifically recognises the recessed 5′ DNA end and fixes the orientation of 9–1–1 on the ssDNA.
Selective pericentromeric heterochromatin dismantling caused by TP53 activation during senescence
Authors: Mendez-Bermudez Aaron , Lototska Liudmyla , Pousse Melanie , Tessier Florent , Croce Oliver , Latrick Chrysa M , Cherdyntseva Veronica , Nassour Joe , Xiaohua Jiang , Lu Yiming , Abbadie Corinne , Gagos Sarantis , Ye Jing , Gilson Eric
Published: July 2022

Cellular senescence triggers various types of heterochromatin remodeling that contribute to aging. However, the age-related mechanisms that lead to these epigenetic alterations remain elusive. Here, we asked how two key aging hallmarks, telomere shortening and constitutive heterochromatin loss, are mechanistically connected during senescence. We show that, at the onset of senescence, pericentromeric heterochromatin is specifically dismantled consisting of chromatin decondensation, accumulation of DNA breakages, illegitimate recombination and loss of DNA. This process is caused by telomere shortening or genotoxic stress by a sequence of events starting from TP53-dependent downregulation of the telomere protective protein TRF2. The resulting loss of TRF2 at pericentromeres triggers DNA breaks activating ATM, which in turn leads to heterochromatin decondensation by releasing KAP1 and Lamin B1, recombination and satellite DNA excision found in the cytosol associated with cGAS. This TP53–TRF2 axis activates the interferon response and the formation of chromosome rearrangements when the cells escape the senescent growth arrest. Overall, these results reveal the role of TP53 as pericentromeric disassembler and define the basic principles of how a TP53-dependent senescence inducer hierarchically leads to selective pericentromeric dismantling through the downregulation of TRF2.
Endoplasmic reticulum oxidoreductin provides resilience against reductive stress and hypoxic conditions by mediating luminal redox dynamics
Authors: Ugalde José Manuel , Aller Isabel , Kudrjasova Lika , Schmidt Romy R , Schlößer Michelle , Homagk Maria , Fuchs Philippe , Lichtenauer Sophie , Schwarzländer Markus , Müller-Schüssele Stefanie J , Meyer Andreas J
Published: July 2022

Oxidative protein folding in the endoplasmic reticulum (ER) depends on the coordinated action of protein disulfide isomerases and ER oxidoreductins (EROs). Strict dependence of ERO activity on molecular oxygen as the final electron acceptor implies that oxidative protein folding and other ER processes are severely compromised under hypoxia. Here, we isolated viable Arabidopsis thaliana ero1 ero2 double mutants that are highly sensitive to reductive stress and hypoxia. To elucidate the specific redox dynamics in the ER in vivo, we expressed the glutathione redox potential (EGSH) sensor Grx1-roGFP2iL-HDEL with a midpoint potential of −240 mV in the ER of Arabidopsis plants. We found EGSH values of −241 mV in wild-type plants, which is less oxidizing than previously estimated. In the ero1 ero2 mutants, luminal EGSH was reduced further to −253 mV. Recovery to reductive ER stress induced by dithiothreitol was delayed in ero1 ero2. The characteristic signature of EGSH dynamics in the ER lumen triggered by hypoxia was affected in ero1 ero2 reflecting a disrupted balance of reductive and oxidizing inputs, including nascent polypeptides and glutathione entry. The ER redox dynamics can now be dissected in vivo, revealing a central role of EROs as major redox integrators to promote luminal redox homeostasis.
Neighborhood-Level Predictors of Age-at-First-Diagnosis of Psychotic Disorders: A Swedish Register-Based Cohort Study
Authors: Spyridonidis Spyros , Dykxhoorn Jennifer , Hollander Anna-Clara , Dalman Christina , Kirkbride James B
Published: July 2022

The relationship between neighborhood-level factors and the incidence of psychotic disorders is well established. However, it is unclear whether neighborhood characteristics are also associated with age-at-first-diagnosis of these disorders. We used linked Swedish register data to identify a cohort of persons first diagnosed with an ICD-10 non-affective or affective psychotic disorder (F20-33) between 1997 and 2016. Using multilevel mixed-effect linear modelling, we investigated whether neighborhood deprivation and population density at birth were associated with age-at-first diagnosis of a psychotic disorder. Our final cohort included 13,440 individuals, with a median age-at-first-diagnosis of 21.8 years for women (interquartile range [IQR]: 19.0–25.5) and 22.9 years for men (IQR: 20.1–26.1; P < .0001). In an unadjusted model, we found no evidence of an association between neighborhood deprivation and age-at-first-diagnosis of psychotic disorder (P = .07). However, after multivariable adjustment, age-at-first-diagnosis increased by .13 years (95% CI: .05 to .21; P = .002) for a one standard deviation increase in neighborhood deprivation. This was equivalent to a later diagnosis of 47 days (95% CI: 18 to 77). We found no evidence of a different relationship for non-affective versus affective psychoses [LRT χ2(1) = .14; P = .71]. Population density was not associated with age-at-first-diagnosis in unadjusted (P = .81) or adjusted (P = .85) models. Later age-at-first-diagnosis for individuals born in more deprived neighborhoods suggests structural barriers in accessing equitable psychiatric care.
Bridging climate change science and policy through TMNs in Turkey: CoM as a boundary-object
Authors: Erbil Aslı Öğüt , Eroğlu Mehmet , Türk Ebru Gönül
Published: July 2022

This paper qualitatively investigates one of the influential transnational municipal networks, Covenant of Mayors for Climate and Energy (CoM)’s position in three Turkish municipal governments in bridging the climate change science and climate change policy gap. In the last two decades, the importance of science-based policymaking for climate mitigation and adaptation and transnational municipal networks empowered by municipalities that guide city policies linked to international agreements has been recognized. In this paper, we argue that CoM has acted as a boundary-object in producing climate change policies and plans in Turkish municipal governments. However, CoM has done so to a certain extent; their effectiveness was limited due to the general atmosphere on climate change policies in Turkey. We substantiate this claim through a two-layer examination: a case-specific analysis of three municipalities and semi-structured interviews with thirteen experts in climate change policy-related issues.
Basal Stem Rot of Oil Palm: The Pathogen, Disease Incidence, and Control Methods
Authors: Zakaria Latiffah
Published: July 2022

Basal stem rot of oil palm caused by Ganoderma boninense is the most serious disease of oil palm in Malaysia, Indonesia, and other oil-palm-producing countries. Economic losses caused by the disease can be up to USD500 million a year. For many years, basal stem rot was found to infect older palm trees of more than 25 to 30 years in age. Only in the 1950s, the disease began to appear in much younger palm trees, 10 to 15 years old, and, in the last decade or so, palm trees as young as 1 year were infected by the disease. The highest incidence occurs in coastal areas of Southeast Asia but the disease has now infected oil palm in inland areas, mainly oil palm planted in peat soils. Disease incidence is also high in areas previously growing coconut or forest. Basal stem rot infection and spread occur through root-to-root contact, and basidiospores that colonize the roots also play a role. In the early stages of infection by G. boninense, the pathogen behaves as a biotroph and later as a necrotroph, secreting cell-wall-degrading enzymes and triggering host defense responses. Genes, gene products, and metabolic pathways involved in oil palm defense mechanisms against G. boninense have been identified and these metabolites have the potential to be used as markers for early detection of the disease. Integrated disease management used to control basal stem rot includes cultural practices, chemical control, and application of biocontrol agents or fertilizers. Early detection tools have also been developed that could assist in management of basal stem rot infections. Development of resistant or tolerant oil palm is still at an early stage; therefore, the existing integrated disease management practices remain the most appropriate methods for managing basal stem rot of oil palm.
The Effects of Skin Temperature Changes on the Integrity of Skin Tissue: A Systematic Review
Authors: Mifsud Tiziana , Modestini Chiara , Mizzi Anabelle , Falzon Owen , Cassar Kevin , Mizzi Stephen
Published: July 2022

OBJECTIVE

To determine whether changes in skin temperature can affect the integrity of skin.

METHODOLOGY

The authors conducted a systematic literature search as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. They searched the CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane, MEDLINE Complete, Academic Search Ultimate, and HyDi databases for articles examining the effects of skin temperature on skin integrity published through April 2020. Two independent reviewers scored the methodologic quality of the 13 included studies.

RESULTS

Only 11 studies were included in the qualitative analysis, as the other two articles had a critical risk of bias. There is strong evidence to indicate that an increase in skin temperature leads to changes in skin structure and function. However, ulcer formation was more affected by intrinsic and extrinsic factors, rather than by temperature alone.

CONCLUSION

Further high-quality randomized controlled trials are required to investigate the direct effect of skin temperature on ulceration.
Understanding Research Methods: Up-and-down Designs for Dose-finding
Authors: Oron Assaf P. , Souter Michael J. , Flournoy Nancy
Published: July 2022

For the task of estimating a target benchmark dose such as the ED50 (the dose that would be effective for half the population), an adaptive dose-finding design is more effective than the standard approach of treating equal numbers of patients at a set of equally spaced doses. Up-and-down is the most popular family of dose-finding designs and is in common use in anesthesiology. Despite its widespread use, many aspects of up-and-down are not well known, implementation is often misguided, and standard, up-to-date reference material about the design is very limited. This article provides an overview of up-and-down properties, recent methodologic developments, and practical recommendations, illustrated with the help of simulated examples. Additional reference material is offered in the Supplemental Digital Content.
The Effects of Lower Extremity Rotational Malalignment on Pediatric Patient-reported Outcomes Measurement and Information System (PROMIS) Scores
Authors: Chandrananth Janan , Hannan Richard , Bouton Daniel , Raney Ellen , Sienko Susan , Do Patrick , Bauer Jeremy P.
Published: July 2022

Background:

There is sparse literature demonstrating the relationship between lower limb pediatric idiopathic rotational malalignment (IRM) and patient-reported outcomes measurement information system (PROMIS) scores. Our goal is to determine and quantify the amount that IRM deformities, as measured with the 3D gait analysis, affect childrens’ pain interference, mobility, and peer relationship PROMIS domains. Secondary outcomes include investigating the potential relationships between IRM and various subgroups (Pediatric Outcomes Data Collection Instrument (PODCI), gender, Body Mass Index (BMI), femur Versus tibia). We also examine whether the PROMIS domains correlate with PODCI in this population.

Methods:

This study was a retrospective cohort, single institution, and consecutively recruited cases series. We identified 47 children over a 3-year period who were evaluated at the motion analysis center at our tertiary care hospital, with increased torsion of the femur or tibia. After exclusions, 25 children with IRM, documented PROMIS data and gait analysis were considered.

Results:

Femoral malrotation had a significant relationship with female gender (P=0.001) and increased BMI (P<0.001). Femoral malrotation had a correlation with PROMIS pain interference (P=0.016), whereas tibial rotation did not achieve significance (P=0.084). In the ANOVA regression analysis, there was a strong prediction of the PROMIS mobility domain when both malrotation and pain interference were present (P=0.007). There were Pearson Correlations of PROMIS and PODCI domains for Mobility Versus Sports (P=0.007) and Pain Interference Versus Comfort/Pain (P=0.004), respectively.

Conclusion:

The evident relationship between lower limb rotational malalignment and PROMIS scores signifies the likelihood for gait and pain disturbance. This in turn could show us that children are likely to be more debilitated and thus may benefit from timely correction. We aim to conduct this as a multicentre trial to confirm our findings.

Level of Evidence:

Level IV.
Aberrant Circulating SNHG1 Serves as a Biomarker to Distinguish Acute Myocardial Infarction and Construction of a Risk Model for Secondary Heart Failure
Authors: Yang Guanghu , Gai Xin , Han Maozhi , Gao Feng , Qiao Lujun , Tian Yonggang
Published: July 2022

Acute myocardial infarction (AMI) is a severe condition observed in patients with coronary heart disease, and heart failure (HF) often occurs after AMI. This study aimed to evaluate the clinical significance of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in the diagnosis and prognosis of AMI and to construct a logistic predict model to determine the risk of post-AMI HF. This study analyzed the data of 229 patients with AMI. Serum SNHG1 levels were examined using quantitative real-time PCR, and its diagnostic value was evaluated using receiver operating characteristic analysis. The predictive value of SNHG1 for HF onset was evaluated using the Kaplan–Meier method and Cox regression analysis. The risk factors and predictive parameters included in the predictive model of post-AMI HF were determined using multivariate logistic regression analysis. In this study, we found that reduced serum SNHG1 was negatively correlated with the Gensini score of patients with AMI. The diagnostic performance of combining cardiac troponin I (cTnI) and creatine kinase (CK)-MB and SNHG1 was the best. Lower SNHG1 expression served as an independent indicator for HF secondary to AMI. A logistic risk model was constructed with the following equation:

, and the predictive accuracy of this model was relatively high with an area under the curve of 0.890. Taken together, our results revealed that reduced SNHG1 combining cTnI and CK-MB had the best diagnostic performance in patients with AMI. A logistic risk model based on SNHG1, age, cTnI, CK-MB, left ventricular ejection fraction, and Gensini score may help to determine the development of HF in patients with AMI.
Uterine arcuate artery calcification as a potential marker of cardiovascular risk—a preliminary study
Authors: Akilli Rabia , Kucukgoz Gulec Umran , Deniz Ali , Aikimbaev Kairqueldy , Akcabay Cigdem , Seydaoglu Gulsah
Published: July 2022

Objective

Atherosclerotic cardiovascular disease is the most common cause of death in postmenopausal women. As this is a progressive disease, it is important to identify markers at an early stage during the subclinical period. Arterial calcifications are an indicator of overall atherosclerotic disease and therefore may be used as a marker for the estimation of future atherosclerotic cardiovascular events. The aims of this study are to investigate the relationship between uterine myometrial calcification (UMC) and carotid artery intima-media thickness (CIMT) and to evaluate whether UMC can be a predictive marker for the estimation of future atherosclerotic cardiovascular risk in asymptomatic postmenopausal women.

Methods

In this cross-sectional study, we assessed 81 postmenopausal women without gynecological complaints for cardiovascular risk factors, UMC, and CIMT. Participants were divided into two risk groups according to their cardiovascular risk factors. The level of UMC was determined using a new scoring system, which was based on transvaginal ultrasonography. Demographic, clinical, and laboratory parameters, UMC scores, and measurements of CIMT were evaluated.

Results

A moderately positive correlation was detected between CIMT and UMC scores (r = 0.62). There was a significant relationship between UMC scores and atherosclerotic cardiovascular risk; the risk of atherosclerosis was 15.4 times higher (OR: 15.4, 95% CI: 5.1–46.8; P = 0.001) in participants with a high UMC score (≥2). According to the multivariable logistic regression model adjusted by age and duration of menopause, the risk of cardiovascular atherosclerosis increased 27.8 fold for those with CIMT of 0.075 or greater (OR: 27.8, 95% CI: 5.3–147.1; P = 0.001) and 9.2 fold for those with a UMC score of 2 or greater (OR: 9.2, CI: 1.22–69.3; P = 0.032).

Conclusions

The presence of UMC has been identified as an independent predictive factor for atherosclerotic risk. Accordingly, considering UMC as an atherosclerotic cardiovascular risk factor may provide an opportunity to identify cardiovascular disease in asymptomatic postmenopausal women. When UMC is detected, women should be assessed for cardiovascular risk.
Artificial intelligence in ophthalmology: an insight into neurodegenerative disease
Authors: Patil Ajay D. , Biousse Valérie , Newman Nancy J.
Published: July 2022

Purpose of review

The aging world population accounts for the increasing prevalence of neurodegenerative diseases such as Alzheimer's and Parkinson's which carry a significant health and economic burden. There is therefore a need for sensitive and specific noninvasive biomarkers for early diagnosis and monitoring. Advances in retinal and optic nerve multimodal imaging as well as the development of artificial intelligence deep learning systems (AI-DLS) have heralded a number of promising advances of which ophthalmologists are at the forefront.

Recent findings

The association among retinal vascular, nerve fiber layer, and macular findings in neurodegenerative disease is well established. In order to optimize the use of these ophthalmic parameters as biomarkers, validated AI-DLS are required to ensure clinical efficacy and reliability. Varied image acquisition methods and protocols as well as variability in neurogenerative disease diagnosis compromise the robustness of ground truths that are paramount to developing high-quality training datasets.

In order to produce effective AI-DLS for the diagnosis and monitoring of neurodegenerative disease, multicenter international collaboration is required to prospectively produce large inclusive datasets, acquired through standardized methods and protocols. With a uniform approach, the efficacy of resultant clinical applications will be maximized.
Blinding and sham control methods in trials of physical, psychological, and self-management interventions for pain (article I): a systematic review and description of methods
Authors: Hohenschurz-Schmidt David , Draper-Rodi Jerry , Vase Lene , Scott Whitney , McGregor Alison , Soliman Nadia , MacMillan Andrew , Olivier Axel , Cherian Cybill Ann , Corcoran Daniel , Abbey Hilary , Freigang Sascha , Chan Jessica , Phalip Jules , Nørgaard Sørensen Lea , Delafin Maite , Baptista Margarida , Medforth Naomi R. , Ruffini Nuria , Skøtt Andresen Stephanie , Ytier Sylvain , Ali Dorota , Hobday Harriet , Santosa Anak Agung Ngurah Agung Adhiyoga , Vollert Jan , Rice Andrew S.C.
Published: July 2022

Blinding is challenging in randomised controlled trials of physical, psychological, and self-management therapies for pain, mainly because of their complex and participatory nature. To develop standards for the design, implementation, and reporting of control interventions in efficacy and mechanistic trials, a systematic overview of currently used sham interventions and other blinding methods was required. Twelve databases were searched for placebo or sham-controlled randomised clinical trials of physical, psychological, and self-management treatments in a clinical pain population. Screening and data extraction were performed in duplicate, and trial features, description of control methods, and their similarity to the active intervention under investigation were extracted (protocol registration ID: CRD42020206590). The review included 198 unique control interventions, published between 2008 and December 2021. Most trials studied people with chronic pain, and more than half were manual therapy trials. The described control interventions ranged from clearly modelled based on the active treatment to largely dissimilar control interventions. Similarity between control and active interventions was more frequent for certain aspects (eg, duration and frequency of treatments) than others (eg, physical treatment procedures and patient sensory experiences). We also provide an overview of additional, potentially useful methods to enhance blinding, as well as the reporting of processes involved in developing control interventions. A comprehensive picture of prevalent blinding methods is provided, including a detailed assessment of the resemblance between active and control interventions. These findings can inform future developments of control interventions in efficacy and mechanistic trials and best-practice recommendations.