bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Stresses and Strains in Stainless Steel 316 L Tubes Subjected to Die Expansion
Authors: Zhao Zijian , Bouzid Abdel-Hakim , Laghzale Nor-Eddine
Published: February 2022

SS316 L finned tubes are becoming very popular in high-pressure heat exchangers and particularly in CO2 cooler applications. Due to the high pressures present during operation, these tubes require an accurate residual stress evaluation generated by the die expansion process. Die expansion of air cooler fin tubes creates not only high stresses that can surpass the ultimate tensile strength when combined with operation stresses but microcracks during expansion when the process is not well controlled. This research work aims to study the elastic-plastic behavior and estimate the residual stress state of fin tubes subjected to the die expansion process. The stresses and deformations of the expanded SS316 L tube are analyzed numerically using the finite element method. The expansion and contraction process are modeled considering the elastic–plastic material behavior for different die sizes. The maximum longitudinal, tangential, and contact stresses are evaluated to verify the critical stress state of the joint during the expansion process. The importance of the material behavior in evaluating the residual stresses using kinematic and isotropic hardening is addressed. Finally, an experiment was conducted to assess the tangential and longitudinal strains of a 3/8 in. stainless steel tube subjected to expansion with an oval-shaped die.
Vinculación comunitaria, antropología histórica ngigua y el nacimiento de la UIEP-sur
Authors:   Universidad Veracruzana, Galán López Felipe Javier
Published: February 2022

La ponencia que presentamos es parte del proyecto “Pensar históricamente la vinculación comunitaria”, realizado en conjunto con la sabia de la comunidad ngigua-popoloca de San Marcos Tlacoyalco, la profesora Verónica Luna Villanueva, en el municipio de Tlacotepec de Benito Juárez en el sureste del estado de Puebla y con cuatro brigadas de estudiantes, de quienes aparecen sus nombres en este trabajo, en la unidad académica sur, que inició funciones en el mes de agosto del año 2019. La experiencia presentada tiene que ver con el trabajo como profesores del curso Estrategias de Vinculación con la comunidad, realizada durante el semestre agosto-diciembre de 2019, parte de este trabajo ha sido publicado en la revista Ra XinHai, Volumen 17, número 2 / Julio - diciembre 2021.
Raising students' interest and deepening their training in acoustics through dedicated exercises
Authors: Potel Catherine , Bruneau Michel , Gatignol Philippe , Lanceleur Patrick
Published: February 2022

The aim of this paper is to briefly present ways to improve the interest of students who begin to attend physical acoustic courses and give examples of exercises (among many others) dedicated to the deepening of their training. Regarding the interest of students who are just beginning, two particular questions arise: how is the attention of these students gained? and how would the students be properly trained when starting out? An attempt to answer these questions is given at the beginning of the paper. Then, the paper continues with a brief presentation of some problems, which are extracted from a three-volume textbook that was published recently, precisely posed, and solved in detail analytically in an exact or approximate manner, even numerically, according to the three levels (bachelor, master, and Ph.D.) while offering an opportunity to deal extensively with the modeling of important topics in acoustics, which are treated as having several ways to be addressed.
Using volumetric optical coherence tomography to achieve spatially resolved organ of Corti vibration measurements
Authors: Frost Brian L. , Strimbu Clark Elliott , Olson Elizabeth S.
Published: February 2022

Optical coherence tomography (OCT) has become a powerful tool for measuring vibrations within the organ of Corti complex (OCC) in cochlear mechanics experiments. However, the one-dimensional nature of OCT measurements, combined with experimental and anatomical constraints, make these data ambiguous: Both the relative positions of measured structures and their orientation relative to the direction of measured vibrations are not known a priori. We present a method by which these measurement features can be determined via the use of a volumetric OCT scan to determine the relationship between the imaging/measurement axes and the canonical anatomical axes. We provide evidence that the method is functional by replicating previously measured radial vibration patterns of the basilar membrane (BM). We used the method to compare outer hair cell and BM vibration phase in the same anatomical cross section (but different optical cross sections), and found that outer hair cell region vibrations lead those of the BM across the entire measured frequency range. In contrast, a phase lead is only present at low frequencies in measurements taken within a single optical cross section. Relative phase is critical to the workings of the cochlea, and these results emphasize the importance of anatomically oriented measurement and analysis.
A balanced Oct4 interactome is crucial for maintaining pluripotency
Authors: Han Dong , Wu Guangming , Chen Rui , Drexler Hannes C. A. , MacCarthy Caitlin M. , Kim Kee-Pyo , Adachi Kenjiro , Gerovska Daniela , Mavrommatis Lampros , Bedzhov Ivan , Araúzo-Bravo Marcos J. , Schöler Hans R.
Published: February 2022

Oct4 collaborates primarily with other transcriptional factors or coregulators to maintain pluripotency. However, how Oct4 exerts its function is still unclear. Here, we show that the Oct4 linker interface mediates competing yet balanced Oct4 protein interactions that are crucial for maintaining pluripotency. Oct4 linker mutant embryonic stem cells (ESCs) show decreased expression of self-renewal genes and increased expression of differentiation genes, resulting in impaired ESC self-renewal and early embryonic development. The linker mutation interrupts the balanced Oct4 interactome. In mutant ESCs, the interaction between Oct4 and Klf5 is decreased. In contrast, interactions between Oct4 and Cbx1, Ctr9, and Cdc73 are increased, disrupting the epigenetic state of ESCs. Control of the expression level of Klf5, Cbx1, or Cdc73 rebalances the Oct4 interactome and rescues the pluripotency of linker mutant ESCs, indicating that such factors interact with Oct4 competitively. Thus, we provide previously unidentified molecular insights into how Oct4 maintains pluripotency.
Ultrarapid lytic granule release from CTLs activates Ca
2+
-dependent synaptic resistance pathways in melanoma cells
Authors: Filali Liza , Puissegur Marie-Pierre , Cortacero Kevin , Cussat-Blanc Sylvain , Khazen Roxana , Van Acker Nathalie , Frenois François-Xavier , Abreu Arnaud , Lamant Laurence , Meyer Nicolas , Vergier Béatrice , Müller Sabina , McKenzie Brienne , Valitutti Salvatore
Published: February 2022

Human cytotoxic T lymphocytes (CTLs) exhibit ultrarapid lytic granule secretion, but whether melanoma cells mobilize defense mechanisms with commensurate rapidity remains unknown. We used single-cell time-lapse microscopy to offer high spatiotemporal resolution analyses of subcellular events in melanoma cells upon CTL attack. Target cell perforation initiated an intracellular Ca
2+
wave that propagated outward from the synapse within milliseconds and triggered lysosomal mobilization to the synapse, facilitating membrane repair and conferring resistance to CTL induced cytotoxicity. Inhibition of Ca
2+
flux and silencing of synaptotagmin VII limited synaptic lysosomal exposure and enhanced cytotoxicity. Multiplexed immunohistochemistry of patient melanoma nodules combined with automated image analysis showed that melanoma cells facing CD8
+
CTLs in the tumor periphery or peritumoral area exhibited significant lysosomal enrichment. Our results identified synaptic Ca
2+
entry as the definitive trigger for lysosomal deployment to the synapse upon CTL attack and highlighted an unpredicted defensive topology of lysosome distribution in melanoma nodules.
A novel pathway for multiscale high-resolution time-resolved residual stress evaluation of laser-welded Eurofer97
Authors: Zhu Bin , Wang Yiqiang , Dluhoš Jiří , London Andy J. , Gorley Michael , Whiting Mark J. , Sui Tan
Published: February 2022

The plasma-facing components of future fusion reactors, where the Eurofer97 is the primary structural material, will be assembled by laser-welding techniques. The heterogeneous residual stress induced by welding can interact with the microstructure, resulting in a degradation of mechanical properties and a reduction in joint lifetime. Here, a Xe
+
plasma focused ion beam with digital image correlation (PFIB-DIC) and nanoindentation is used to reveal the mechanistic connection between residual stress, microstructure, and microhardness. This study is the first to use the PFIB-DIC to evaluate the time-resolved multiscale residual stress at a length scale of tens of micrometers for laser-welded Eurofer97. A nonequilibrium microscale residual stress is observed, which contributes to the macroscale residual stress. The microhardness is similar for the fusion zone and heat-affected zone (HAZ), although the HAZ exhibits around ~30% tensile residual stress softening. The results provide insight into maintaining structural integrity for this critical engineering challenge.
KIX domain determines a selective tumor-promoting role for EP300 and its vulnerability in small cell lung cancer
Authors: Kim Kee-Beom , Kabra Ashish , Kim Dong-Wook , Xue Yongming , Huang Yuanjian , Hou Pei-Chi , Zhou Yunpeng , Miranda Leilani J. , Park Jae-Il , Shi Xiaobing , Bender Timothy P. , Bushweller John H. , Park Kwon-Sik
Published: February 2022

EP300, a transcription coactivator important in proliferation and differentiation, is frequently mutated in diverse cancer types, including small cell lung cancer (SCLC). While these mutations are thought to result in loss of EP300 function, the impact on tumorigenesis remains largely unknown. Here, we demonstrate that EP300 mutants lacking acetyltransferase domain accelerate tumor development in mouse models of SCLC. However, unexpectedly, complete
Ep300
knockout suppresses SCLC development and proliferation. Dissection of EP300 domains identified kinase inducible domain-interacting (KIX) domain, specifically its interaction with transcription factors including MYB, as the determinant of protumorigenic activity. Ala
627
in EP300 KIX results in a higher protein-binding affinity than Asp
647
at the equivalent position in CREBBP KIX, underlying the selectivity of KIX-binding partners for EP300. Blockade of KIX-mediated interactions inhibits SCLC development in mice and cell growth. This study unravels domain-specific roles for EP300 in SCLC and unique vulnerability of the EP300 KIX domain for therapeutic intervention.
Experimental evidence for long-distance electrodynamic intermolecular forces
Authors: Lechelon Mathias , Meriguet Yoann , Gori Matteo , Ruffenach Sandra , Nardecchia Ilaria , Floriani Elena , Coquillat Dominique , Teppe Frédéric , Mailfert Sébastien , Marguet Didier , Ferrier Pierre , Varani Luca , Sturgis James , Torres Jeremie , Pettini Marco
Published: February 2022

Both classical and quantum electrodynamics predict the existence of dipole-dipole long-range electrodynamic intermolecular forces; however, these have never been hitherto experimentally observed. The discovery of completely new and unanticipated forces acting between biomolecules could have considerable impact on our understanding of the dynamics and functioning of the molecular machines at work in living organisms. Here, using two independent experiments, on the basis of different physical effects detected by fluorescence correlation spectroscopy and terahertz spectroscopy, respectively, we demonstrate experimentally the activation of resonant electrodynamic intermolecular forces. This is an unprecedented experimental proof of principle of a physical phenomenon that, having been observed for biomacromolecules and with long-range action (up to 1000 Å), could be of importance for biology. In addition to thermal fluctuations that drive molecular motion randomly, these resonant (and thus selective) electrodynamic forces may contribute to molecular encounters in the crowded cellular space.
Thermostable ionizable lipid-like nanoparticle (iLAND) for RNAi treatment of hyperlipidemia
Authors: Hu Bo , Li Bo , Li Kun , Liu Yuanyuan , Li Chunhui , Zheng Lulu , Zhang Mengjie , Yang Tongren , Guo Shuai , Dong Xiyu , Zhang Tian , Liu Qing , Hussain Abid , Weng Yuhua , Peng Ling , Zhao Yongxiang , Liang Xing-Jie , Huang Yuanyu
Published: February 2022

Small interfering RNA (siRNA) therapeutic is considered to be a promising modality for the treatment of hyperlipidemia. Establishment of a thermostable clinically applicable delivery system remains a most challenging issue for siRNA drug development. Here, a series of ionizable lipid-like materials were rationally designed; 4 panels of lipid formulations were fabricated and evaluated on the basis of four representative structures. The lead lipid (A1-D1-5) was stable at 40°C, and the optimized formulation (iLAND) showed dose and time dual-dependent gene silencing pattern with median effective dose of 0.18 mg/kg. In addition, potent and durable reduction of serum cholesterol and triglyceride were achieved by administering siRNAs targeting
angiopoietin-like 3
or
apolipoprotein C3
(
APOC3
) in high-fat diet–fed mice, db/db mice, and human
APOC3
transgenic mice, respectively, accompanied by displaying ideal safety profiles. Therefore, siRNA@iLAND prepared with thermostable A1-D1-5 demonstrates substantial value for siRNA delivery, hyperlipidemia therapy, and prevention of subsequent metabolic diseases.
Antimicrobial production by perifollicular dermal preadipocytes is essential to the pathophysiology of acne
Authors: O’Neill Alan M. , Liggins Marc C. , Seidman Jason S. , Do Tran H. , Li Fengwu , Cavagnero Kellen J. , Dokoshi Tatsuya , Cheng Joyce Y. , Shafiq Faiza , Hata Tissa R. , Gudjonsson Johann E. , Modlin Robert L. , Gallo Richard L.
Published: February 2022

Innate immune defense against deep tissue infection by
Staphylococcus aureus
is orchestrated by fibroblasts that become antimicrobial when triggered to differentiate into adipocytes. However, the role of this process in noninfectious human diseases is unknown. To investigate the potential role of adipogenesis by dermal fibroblasts in acne, a disorder triggered by
Cutibacterium acnes
, single-cell RNA sequencing was performed on human acne lesions and mouse skin challenged by
C. acnes
. A transcriptome consistent with adipogenesis was observed within specific fibroblast subsets from human acne and mouse skin lesions infected with
C. acnes
. Perifollicular dermal preadipocytes in human acne and mouse skin lesions showed colocalization of PREF1, an early marker of adipogenesis, and cathelicidin (
Camp
), an antimicrobial peptide. This capacity of
C. acnes
to specifically trigger production of cathelicidin in preadipocytes was dependent on TLR2. Treatment of wild-type mice with retinoic acid (RA) suppressed the capacity of
C. acnes
to form acne-like lesions, inhibited adipogenesis, and enhanced cathelicidin expression in preadipocytes, but lesions were unresponsive in
Camp
−/−
mice, despite the anti-adipogenic action of RA. Analysis of inflamed skin of acne patients after retinoid treatment also showed enhanced induction of cathelicidin, a previously unknown beneficial effect of retinoids in difficult-to-treat acne. Overall, these data provide evidence that adipogenic fibroblasts are a critical component of the pathogenesis of acne and represent a potential target for therapy.
Whole-Genome Sequencing Has the Potential To Improve Treatment for Rifampicin-Resistant Tuberculosis in High-Burden Settings: a Retrospective Cohort Study
Authors: Cox Helen , Goig Galo A. , Salaam-Dreyer Zubeida , Dippenaar Anzaan , Reuter Anja , Mohr-Holland Erika , Daniels Johnny , Cudahy Patrick G. T. , Nicol Mark P. , Borrell Sonia , Reinhard Miriam , Doetsch Anna , Beisel Christian , Gagneux Sebastien , Warren Robin M. , Furin Jennifer
Published: February 2022

Treatment of multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB), although improved in recent years with shorter, more tolerable regimens, remains largely standardized and based on limited drug susceptibility testing (DST). More individualized treatment with expanded DST access is likely to improve patient outcomes.
Antiviral RNAi Response against the Insect-Specific Agua Salud Alphavirus
Authors: Altinli Mine , Leggewie Mayke , Badusche Marlis , Gyanwali Rashwita , Scherer Christina , Schulze Jonny , Sreenu Vattipally B. , Fegebank Marvin , Zibrat Bernhard , Fuss Janina , Junglen Sandra , Schnettler Esther
Published: February 2022

Mosquitoes are efficient vectors for many arboviruses that cause emergent infectious diseases in humans. Many insect-specific viruses (ISVs) that can infect mosquitoes but cannot infect vertebrates have been discovered in the last decade.
Genetic Homology between Bacteria Isolated from Pulmonary Abscesses or Pyothorax and Bacteria from the Oral Cavity
Authors: Katsuda Rinko , Inubushi Junya , Tobata Haruko , Eguchi Toru , Terada Kunihiko , Kagami Ryogo , Kawamura Tetsuji , Kajiwara Yoshihiro , Nakahara Yasuharu
Published: February 2022

We present direct genetic evidence that some of the bacteria in pulmonary abscesses and pyothorax are derived from the oral flora. This is the first report describing the presence of genetically homologous strains both in pus from pulmonary abscesses and pyothorax and in swab samples from the mouth.
Pufferfish (Tetraodon cutcutia) Sampled from a Freshwater River Serves as an Intermediate Reservoir of a Sucrose Nonfermenting Variant of Vibrio cholerae PS-4
Authors: Das Lipika , Deb Sushanta , Arakawa Eiji , Yamasaki Shinji , Das Subrata K.
Published: February 2022

Vibrio choleraeis native of aquatic environments. In general,V. choleraeferments sucrose on thiosulfate citrate bile salt sucrose (TCBS) agar and produces yellow colonies.V. choleraestrain PS-4 described in this study is a sucrose nonfermenting variant associated with pufferfish skin and does not produce yellow colonies on TCBS agar.
Lipid and Nucleocapsid N-Protein Accumulation in COVID-19 Patient Lung and Infected Cells
Authors: Grootemaat Anita E. , van der Niet Sanne , Scholl Edwin R. , Roos Eva , Schurink Bernadette , Bugiani Marianna , Miller Sara E. , Larsen Per , Pankras Jeannette , Reits Eric A. , van der Wel Nicole N.
Published: February 2022

Visualization of the subcellular localization of SARS-CoV-2 proteins in lung patient material of COVID-19 patients is important for the understanding of this new virus. We detected viral proteins in the context of the ultrastructure of infected cells and tissues and discovered that some viral proteins accumulate in novel, lipid-filled compartments.
Drug-Resistant Characteristics, Genetic Diversity, and Transmission Dynamics of Rifampicin-Resistant Mycobacterium tuberculosis in Hunan, China, Revealed by Whole-Genome Sequencing
Authors: He Wencong , Tan Yunhong , Liu Chunfa , Wang Yiting , He Ping , Song Zexuan , Liu Dongxin , Zheng Huiwen , Ma Aijing , Zhao Bing , Ou Xichao , Xia Hui , Wang Shengfen , Zhao Yanlin
Published: February 2022

Comprehensive information such as genetic background and drug-resistant profile of TB strains could help to tailor public interventions. However, these data are limited in Hunan province, one of the provinces with high-TB burden in China.
Effect of Tranexamic Acid against Staphylococcus spp. and Cutibacterium acnes Associated with Peri-Implant Infection: Results from an
In Vitro
Study
Authors: Benjumea Antonio , Díaz-Navarro Marta , Hafian Rama , Sánchez-Somolinos Mar , Vaquero Javier , Chana Francisco , Muñoz Patricia , Guembe María
Published: February 2022

The possible use of TXA as an antibiotic agent in addition to its antifibrinolytic effect may play an important role in the prevention of prosthetic joint infection.
Elevated Cytokine Levels in Plasma of Patients with SARS-CoV-2 Do Not Contribute to Pulmonary Microvascular Endothelial Permeability
Authors: Kovacs-Kasa Anita , Zaied Abdelrahman A. , Leanhart Silvia , Koseoglu Murat , Sridhar Supriya , Lucas Rudolf , Fulton David J. , Vazquez Jose A. , Annex Brian H.
Published: February 2022

Lung vascular endothelial injury in SARS-CoV-2 patients is one of the most important causes of morbidity and mortality and has been linked to more severe complications including acute respiratory distress syndrome (ARDS) and subsequent death due to multiorgan failure. We have demonstrated that in eight consecutive patients with SARS-CoV-2, who were not selected for evidence of endothelial injury, the diluted plasma induced intense lung microvascular damage,
in vitro
.
Safety and Effectiveness of Isavuconazole Treatment for Fungal Infections in Solid Organ Transplant Recipients (ISASOT Study)
Authors: Monforte Arnau , Los-Arcos Ibai , Martín-Gómez Maria Teresa , Campany-Herrero David , Sacanell Judith , Berastegui Cristina , Márquez-Algaba Ester , Sempere Abiu , Nuvials Xavier , Deu Maria , Castells Lluís , Moreso Francesc , Bravo Carles , Gavaldà Joan , Len Oscar
Published: February 2022

We describe 53 solid organ transplant recipients treated with isavuconazole for fungal infections. Because its use in clinical practice, there is scarce data of its use in solid organ transplant recipients, where interactions with calcineurin inhibitors and mTOR and adverse drug events have limited the use of other triazoles.
Characterization of a Novel Linezolid Resistance Gene
optrA
and Bacitracin Resistance Locus-Carrying Multiple Antibiotic Resistant Integrative and Conjugative Element ICE
Ssu
1112S in
Streptococccus Suis
Authors: Yang Yingying , Kuang Xiuhua , Han Rong-jia , Zhai Ya-jun , He Dan-dan , Zhao Jin-feng , Liu Jian-hua , Hu Gong-zheng
Published: February 2022

Antimicrobial resistance (AMR) caused by the imprudent use of antimicrobials has become a global problem, which poses a serious threat to treatment of
S. suis
infection in pigs and humans. Importantly, AMR genes can horizontally spread among commensal organisms and pathogenic microbiota, thereby accelerating the dissemination of AMR determinants.
Comparison between Nasal and Nasopharyngeal Swabs for SARS-CoV-2 Rapid Antigen Detection in an Asymptomatic Population, and Direct Confirmation by RT-PCR from the Residual Buffer
Authors: Patriquin Glenn , LeBlanc Jason J. , Williams Catherine , Hatchette Todd F. , Ross John , Barrett Lisa , Davidson Ross
Published: February 2022

Nasal swabbing for SARS-CoV-2 (COVID-19) comes with many benefits but is slightly less sensitive than traditional nasopharyngeal swabbing; however, confirmatory lab-based testing could be performed directly from the residual buffer from either sample type.
How similar was the 1983Mw 6.9 Borah Peak earthquake rupture to its surface-faulting predecessors along the northern Lost River fault zone (Idaho, USA)?
Authors: DuRoss Christopher B. , Briggs Richard W. , Gold Ryan D. , Hatem Alexandra E. , Elliott Austin J. , Delano Jaime , Medina-Cascales Ivan , Gray Harrison J. , Mahan Shannon A. , Nicovich Sylvia R. , Lifton Zachery M. , Kleber Emily , McDonald Greg , Hiscock Adam , Bunds Michael , Reitman Nadine G.
Published: February 2022

We excavated trenches at two paleoseismic sites bounding a trans-basin bedrock ridge (the Willow Creek Hills) along the northern Lost River fault zone to explore the uniqueness of the 1983 Mw 6.9 Borah Peak earthquake compared to its prehistoric predecessors. At the Sheep Creek site on the southernmost Warm Springs section, two earthquakes occurred at 9.8–14.0 ka (95% confidence) and 6.5–7.1 ka; each had ~1.9 m of vertical displacement. About 4 km to the southeast, across the Willow Creek Hills, two ruptures at the Arentson Gulch site on the northernmost Thousand Springs section occurred at 9.0–14.7 ka and 6.1–7.5 ka with ~1.9 m of vertical displacement each. We synthesize these and previous paleoseismic results into a model of five postglacial (<15 ka) ruptures along a ~65 km reach of the northern Lost River fault zone. Our results show that the Borah Peak earthquake (34 km; 0.9 m mean displacement) was unique compared to previous ruptures that had both longer and shorter rupture lengths (~25–38 km), more displacement (mean of ~1.3–1.4 m), and equal or greater magnitude (Mw 6.9–7.1) than that in the 1983 earthquake. These ruptures support a hypothesis of variable rupture length and displacement on the northern Lost River fault zone and show that predecessors to the 1983 rupture have passed unimpeded through the Willow Creek Hills. Our work demonstrates that normal faults are capable of producing variable spatial-temporal patterns of rupture that, together with comparisons of fault geometry and historical rupture length, improve our understanding of fault segmentation and help inform models of earthquake rupture probability.
Development of a core outcome set for multimorbidity trials in low/middle-income countries (COSMOS): study protocol
Authors: Boehnke Jan R. , Rana Rusham Zahra , Kirkham Jamie J. , Rose Louise , Agarwal Gina , Barbui Corrado , Chase-Vilchez Alyssa , Churchill Rachel , Flores-Flores Oscar , Hurst John R. , Levitt Naomi , van Olmen Josefien , Purgato Marianna , Siddiqi Kamran , Uphoff Eleonora , Vedanthan Rajesh , Wright Judy , Wright Kath , Zavala Gerardo A. , Siddiqi Najma
Published: February 2022

Introduction

‘Multimorbidity’ describes the presence of two or more long-term conditions, which can include communicable, non-communicable diseases, and mental disorders. The rising global burden from multimorbidity is well documented, but trial evidence for effective interventions in low-/middle-income countries (LMICs) is limited. Selection of appropriate outcomes is fundamental to trial design to ensure cross-study comparability, but there is currently no agreement on a core outcome set (COS) to include in trials investigating multimorbidity specifically in LMICs. Our aim is to develop international consensus on two COSs for trials of interventions to prevent and treat multimorbidity in LMIC settings.

Methods and analysis

Following methods recommended by the Core Outcome Measures in Effectiveness Trials initiative, the development of these two COSs will occur in parallel in three stages: (1) generation of a long list of potential outcomes for inclusion; (2) two-round online Delphi surveys and (3) consensus meetings. First, to generate an initial list of outcomes, we will conduct a systematic review of multimorbidity intervention and prevention trials and interviews with people living with multimorbidity and their caregivers in LMICs. Outcomes will be classified using an outcome taxonomy. Two-round Delphi surveys will be used to elicit importance scores for these outcomes from people living with multimorbidity, caregivers, healthcare professionals, policy makers and researchers in LMICs. Finally, consensus meetings including all of these stakeholders will be held to agree outcomes for inclusion in the two COSs.

Ethics and dissemination

The study has been approved by the Research Governance Committee of the Department of Health Sciences, University of York, UK (HSRGC/2020/409/D:COSMOS). Each participating country/research group will obtain local ethics board approval. Informed consent will be obtained from all participants. We will disseminate findings through peer-reviewed open access publications, and presentations at global conferences selected to reach a wide range of LMIC stakeholders.

PROSPERO registation number

CRD42020197293.
Incidence, clinical characteristics and long-term prognosis of postoperative symptomatic venous thromboembolism: a retrospective cohort study
Authors: Takeda Chikashi , Yamashita Yugo , Takeuchi Masato , Yonekura Hiroshi , Dong Li , Hamada Miho , Hirotsu Akiko , Ono Koh , Kawakami Koji , Fukuda Kazuhiko , Morimoto Takeshi , Kimura Takeshi , Mizota Toshiyuki
Published: February 2022

Objectives

The purpose of this study was to evaluate the incidence, clinical characteristics and prognosis of postoperative symptomatic venous thromboembolism (VTE) in Japan.

Design

Retrospective observational study. Two data sets, Contemporary ManageMent AND outcomes in patients with Venous ThromboEmbolism (COMMAND VTE) Registry and Japanese Society of Anesthesiologists (JSA) annual report, were used for current analyses.

Setting

Eighteen of 29 centres participated in the COMMAND VTE Registry.

Participants

Acute symptomatic patients with VTE who had undergone surgery 2 months prior to the diagnosis at 18 centres from January 2010 to December 2013 were identified in the COMMAND VTE Registry. From each centre’s JSA annual report, the overall population that had received anaesthetic management during this period was retrieved.

Interventions

None.

Primary and secondary outcome measures

The primary outcome was the incidences and clinical characteristics of postoperative symptomatic VTE. The secondary outcomes were recurrent VTE, major bleeding and all-cause death.

Results

We identified 137 patients with postoperative symptomatic VTE, including 57 patients with pulmonary embolism. The incidences of postoperative symptomatic VTE and pulmonary embolism were 0.067% and 0.028%, respectively, based on data from 2 03 943 patients who underwent surgery, managed by anaesthesiologists, during the study period. The incidences of postoperative symptomatic VTE varied widely, depending on surgical and anaesthetic characteristics. Postoperative symptomatic VTE occurred at a median of 8 days after surgery, with 58 patients (42%) diagnosed within 7 days. The cumulative incidence, 30 days after VTE, of recurrent VTE, major bleeding, and all-cause death was 3.0%, 5.2%, and 3.7%, respectively.

Conclusion

This study, combining the large real-world VTE and anaesthesiology databases in Japan revealed the incidence, clinical features and prognosis of postoperative symptomatic VTE, providing useful insights for all healthcare providers involved in various surgeries.

Trial registration

Not applicable.
Protocol for the Lovisenberg Open Acute Door Study (LOADS): a pragmatic randomised controlled trial to compare safety and coercion between open-door policy and usual-care services in acute psychiatric inpatients
Authors: Kunøe Nikolaj , Nussle Hans Martin , Indregard Anne-Marthe
Published: February 2022

Introduction

The reduction of coercion in psychiatry is a high priority for both the WHO and many member countries. Open-door policy (ODP) is a service model for psychiatric ward treatment that prioritises collaborative and motivational measures to better achieve acute psychiatric safety - and treatment objectives. Keeping the ward main door open is one such measure. Evidence on the impact of ODP on coercion and violent events is mixed, and only one randomised controlled trial (RCT) has previously compared ODP to standard practice. The main objectives of the Lovisenberg Open Acute Door Study (LOADS) are to implement and evaluate a Nordic version of ODP for acute psychiatric inpatient services. The evaluation is designed as a pragmatic RCT with treatment-as-usual (TAU) control followed by a 4-year observational period.

Methods and analysis

In this 12-month pragmatic randomised trial, all patients referred to acute ward care will be randomly allocated to either TAU or ODP wards. The primary outcome is the proportion of patient stays with one or more coercive measures. Secondary outcomes include adverse events involving patients and/or staff, substance use and users’ experiences of the treatment environment and of coercion. The main hypothesis is that ODP services will not be inferior to state-of-the art psychiatric treatment. ODP and TAU wards are determined via ward-level randomisation. Following conclusion of the RCT, a longitudinal observational phase begins designed to monitor any long-term effects of ODP.

Ethics and dissemination

The trial has been approved by the Regional Committees for Medical and Health Research Ethics (REC) in Norway (REC South East #29238), who granted LOADS exemption from consent requirements for all eligible, admitted patients. Data are considered highly sensitive but can be made available on request. Results will be published in peer-reviewed journals and presented at scientific conferences and meetings.

Trial registration number

ISRCTN16876467.

Protocol version

1.4, 21 December 2021.
Management of Crohn’s stricture: medical, endoscopic and surgical therapies
Authors: Ismail Mohamed Saleh , Charabaty Aline
Published: February 2022

Patients with Crohn’s disease are at high risk of presenting with or developing a bowel stricture during the course of their disease. The available therapeutic options to manage a symptomatic Crohn’s stricture include medical therapy (mainly biologics), surgical resection and endoscopic interventions. The choice of therapeutic modality depends on the clinical presentation of the stricture, the nature of the stricture (inflammatory vs fibrotic, primary vs anastomotic) and its anatomical characteristics on endoscopy and imaging (length, number, location of strictures and severity of obstruction). The aim herein is to provide an overview of the comprehensive assessment of a Crohn’s stricture and to review the indications of the different therapeutic modalities, their success rates and their limitations to help clinicians properly evaluate and manage Crohn’s strictures.
PICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system
Authors: Gui Xianyong , Bazarova Alina , del Amor Rocìo , Vieth Michael , de Hertogh Gert , Villanacci Vincenzo , Zardo Davide , Parigi Tommaso Lorenzo , Røyset Elin Synnøve , Shivaji Uday N , Monica Melissa Anna Teresa , Mandelli Giulio , Bhandari Pradeep , Danese Silvio , Ferraz Jose G , Hayee Bu'Hussain , Lazarev Mark , Parra-Blanco Adolfo , Pastorelli Luca , Panaccione Remo , Rath Timo , Tontini Gian Eugenio , Kiesslich Ralf , Bisschops Raf , Grisan Enrico , Naranjo Valery , Ghosh Subrata , Iacucci Marietta
Published: February 2022

Histological remission is evolving as an important treatment target in UC. We aimed to develop a simple histological index, aligned to endoscopy, correlated with clinical outcomes, and suited to apply to an artificial intelligence (AI) system to evaluate inflammatory activity.

Methods

Using a set of 614 biopsies from 307 patients with UC enrolled into a prospective multicentre study, we developed the Paddington International virtual ChromoendoScopy ScOre (PICaSSO) Histologic Remission Index (PHRI). Agreement with multiple other histological indices and validation for inter-reader reproducibility were assessed. Finally, to implement PHRI into a computer-aided diagnosis system, we trained and tested a novel deep learning strategy based on a CNN architecture to detect neutrophils, calculate PHRI and identify active from quiescent UC using a subset of 138 biopsies.

Results

PHRI is strongly correlated with endoscopic scores (Mayo Endoscopic Score and UC Endoscopic Index of Severity and PICaSSO) and with clinical outcomes (hospitalisation, colectomy and initiation or changes in medical therapy due to UC flare-up). A PHRI score of 1 could accurately stratify patients’ risk of adverse outcomes (hospitalisation, colectomy and treatment optimisation due to flare-up) within 12 months. Our inter-reader agreement was high (intraclass correlation 0.84). Our preliminary AI algorithm differentiated active from quiescent UC with 78% sensitivity, 91.7% specificity and 86% accuracy.

Conclusions

PHRI is a simple histological index in UC, and it exhibits the highest correlation with endoscopic activity and clinical outcomes. A PHRI-based AI system was accurate in predicting histological remission.
Comparative analysis between 1-D, 2-D and 3-D carotid web quantification
Authors: Perry da Camara Catarina , Nogueira Raul G , Al-Bayati Alhamza R , Pisani Leonardo , Mohammaden Mahmoud , Allen Jason W , Nahab Fadi , Olive Gadea Marta , Frankel Michael R , Haussen Diogo C
Published: February 2022

Background

Carotid webs (CaW) are now recognized as a cause of ischemic stroke in young patients. The thromboembolic potential appears related to the CaW’s morphology and consequent impact on local flow dynamics. We aim to evaluate the reliability of different measurement methods for the quantification of CaW and their relationship to symptomatic status, presence of large vessel occlusion stroke (LVOS), clot burden and final infarct volume.

Methods

This was a retrospective analysis of the local comprehensive stroke center CaW database (September 2014–July 2019). CT angiograms (CTAs) were reviewed independently by two raters, blinded to the clinical information and laterality of the stroke/transient ischemic attack. CaW were quantified with 1-D (length), 2-D (area) and 3-D (volume) measurements via Osirix software. Final infarct volume was calculated on MRI. Patients with superimposed CaW thrombus and no repeat imaging were excluded.

Results

Forty-eight CaW (37 symptomatic and 11 contralateral/asymptomatic) in 38 patients were included. Mean age (±SD) was 48.7 (±8.5) years, 78.9% were women and 77.1% were black. Inter-rater agreement was 0.921 (p<0.001) for 1-D, 0.930 (p<0.001) for 2-D, and 0.937 (p<0.001) for 3-D CaW measurements. When comparing symptomatic with asymptomatic CaW, mean web length was 3.2 mm versus 2.5 mm (p<0.02), median area was 5.8 versus 5.0 mm2(p=0.35) and median volume was 15.0 versus 10.6 mm3(p<0.04), respectively. CaW with a thinner profile (longer intraluminal projection compared with the base) were more likely to be symptomatic (0.67±0.17 vs 0.88±0.37; p=0.01). Average CaW 1-D and final infarct volume had a weak but positive association (Κ=0.230, p<0.05), while no association among web measurements and the presence of LVOS or clot burden was observed.

Conclusion

CaW dimension quantification (1-D, 2-D and 3-D) is highly reproducible. Linear and volumetric measurements were more strongly associated with symptoms. The impact of CaW size on the presence of LVOS, clot burden and final infarct volume is unclear.
Carbon loss in tile drainage and surface runoff from a clay loam soil after a half century of continuous and rotational cropping
Authors: Yang X.M. , Drury C.F. , Reynolds W.D. , Reeb M.D.
Published: February 2022

Tile drainage and surface runoff are major pathways for pollution of water resources by agricultural nutrients and chemicals. Little is known, however, of the pathways and amounts of carbon entry into water resources from agricultural land. This paper evaluates dissolved organic carbon (DOC) and dissolved inorganic carbon (DIC) losses in tile drainage and surface runoff from a Brookston clay loam after more than a half century of monoculture maize ( Zea mays L.), continuous bluegrass sod ( Poa Pratensis L.), and maize-oat ( Avena sativa L.)–alfalfa ( Medicago sativa L.)–alfalfa rotation. Water loss in tile drainage and surface runoff accounted for 27%, 32%, and 18% of annual precipitation (876 mm) for rotation, monoculture maize, and continuous sod, respectively. Tile drainage comprised 66%–89% of water loss from rotation and continuous sod, but only 15% from monoculture maize, with the remaining 85% of water loss from monoculture maize due to surface runoff. On an annualized basis, the measured dissolved C loss was 79 and 83 kg C ha–1 yr–1) from rotation and continuous sod, respectively, while 49 kg C ha–1 yr–1 was lost from monoculture maize. As up to 9% off-gassing loss of CO2 from water samples was measured, total dissolved carbon losses in tile drainage and runoff water were likely greater. For Brookston clay loam soil, leaching into tile drains was the dominant mechanism for dissolved carbon loss from long-term continuous sod and crop rotation, while surface runoff was the dominant mechanism for dissolved carbon loss from long-term monoculture maize.
Understanding and visualizing the statistical analysis of SN1987A neutrino data
Authors: dos Santos Marcos V. , de Holanda Pedro Cunha
Published: February 2022

The SN1987A detection through neutrinos was an event of great importance in neutrino physics, being the first detection of neutrinos created outside our solar system, and then inaugurating the era of experimental neutrino astronomy. The data have been largely studied in many different analysis, and has presented several challenges in different aspects, since both supernova explosion dynamics and neutrino flavour conversion in such extreme environment still have many unknowns. In addition, the low statistics also invoke the need of unbinned statistical methods to compare any model proposal with data. In this paper we focus on a discussion about the most used statistical analysis interpretation, presenting a pedagogical way to understand and visualize this comparison.
Summation over the gravitational instantons and the temperature of the cosmic background radiation
Authors: Davis Simon
Published: February 2022

In this paper, the contributions of gravitational instantons to the temperature of the cosmic background radiation are evaluated. The comoving number density in the radiation-dominated and matter-dominated eras is derived. In addition to the temperature resulting from expansion of the universe, the mass of the microscopic black holes required to create the thermal energy of the cosmic microwave background radiation is derived.
Source-to-Source Automatic Differentiation of OpenMP Parallel Loops
Authors: Hückelheim Jan , Hascoët Laurent
Published: February 2022

This article presents our work toward correct and efficient automatic differentiation of OpenMP parallel worksharing loops in forward and reverse mode. Automatic differentiation is a method to obtain gradients of numerical programs, which are crucial in optimization, uncertainty quantification, and machine learning. The computational cost to compute gradients is a common bottleneck in practice. For applications that are parallelized for multicore CPUs or GPUs using OpenMP, one also wishes to compute the gradients in parallel. We propose a framework to reason about the correctness of the generated derivative code, from which we justify our OpenMP extension to the differentiation model. We implement this model in the automatic differentiation tool Tapenade and present test cases that are differentiated following our extended differentiation procedure. Performance of the generated derivative programs in forward and reverse mode is better than sequential, although our reverse mode often scales worse than the input programs.
Exploiting Problem Structure in Derivative Free Optimization
Authors: Porcelli Margherita , Toint Philippe L.
Published: February 2022

A structured version of derivative-free random pattern search optimization algorithms is introduced, which is able to exploit coordinate partially separable structure (typically associated with sparsity) often present in unconstrained and bound-constrained optimization problems. This technique improves performance by orders of magnitude and makes it possible to solve large problems that otherwise are totally intractable by other derivative-free methods. A library of interpolation-based modelling tools is also described, which can be associated with the structured or unstructured versions of the initial pattern search algorithm. The use of the library further enhances performance, especially when associated with structure. The significant gains in performance associated with these two techniques are illustrated using a new freely-available release of the Brute Force Optimizer (BFO) package firstly introduced in [Porcelli and Toint
2017
], which incorporates them. An interesting conclusion of the numerical results presented is that providing global structural information on a problem can result in significantly less evaluations of the objective function than attempting to building local Taylor-like models.
Cascaded Structure-Learning Network with Using Adversarial Training for Robust Facial Landmark Detection
Authors: Feng Shenming , Nong Xingzhong , Hu Haifeng
Published: February 2022

Recently, great progress has been achieved on facial landmark detection based on convolutional neural network, while it is still challenging due to partial occlusion and extreme head pose. In this paper, we propose a
Cascaded Structure-Learning Network (CSLN)
with using adversarial training to improve the performance of 2D facial landmark detection by taking the structure of facial landmarks into account. In the first stage, we improve the original stacked hourglass network, which applies a multi-branch module to capture different scales of features, a progressive convolution structure to compensate for the missing structural features in hourglass networks, and a pyramid inception structure to expand the receptive field. Specially, by introducing a discriminator, we use the adversarial training strategy to urge the improved hourglass network for generating more accurate heatmaps. The second stage, which is based on attention mechanism, optimizes the spatial correlations between different facial landmarks by reusing the structural features. Moreover, we propose a novel region loss, which can adaptively allocate proper weights to different regions. In this way, the network can focus more on those occluded landmarks. The experimental results on several datasets,
i.e.
300W, COFW, and AFLW, show that our proposed method achieves superior performance compared with the state-of-the-art methods.
Response Generation by Jointly Modeling Personalized Linguistic Styles and Emotions
Authors: Sun Teng , Wang Chun , Song Xuemeng , Feng Fuli , Nie Liqiang
Published: February 2022

Natural language generation (NLG)
has been an essential technique for various applications, like XiaoIce and Siri, and engaged increasing attention recently. To improve the user experience, several emotion-aware NLG methods have been developed to generate responses coherent with a pre-designated emotion (e.g., the positive or negative). Nevertheless, existing methods cannot generate personalized responses as they frequently overlook the personalized linguistic style. Apparently, different human responsers tend to have different linguistic styles. Inspired by this, in this work, we focus on a novel research theme of
personalized emotion-aware NLG
(
PENLG
), whereby the generated responses should be coherent with the linguistic style of a pre-designated responser and emotion. In particular, we study PENLG under a scenario of generating personalized emotion-aware response for social media post. Yet it faces certain research challenges: (1) the user linguistic styles are implicit and complex by nature, and hence it is hard to learn their representations; and (2) linguistic styles and emotions are usually expressed in different manners in a response, and thus how to convey them properly in the generated responses is not easy. Toward this end, we present a novel scheme of PENLG, named CRobot, which consists of a personalized emotion-aware response generator and two discriminators, i.e.,
general discriminator
and
personalized emotion-aware discriminator
. To be more specific, the post-based and avatar-based user linguistic style modeling methods are incorporated into the encoder-decoder–based generator, while the discriminators are devised to ensure that the generated response is fluent and consistent with both the emotion and the linguistic style of the user. Different from the traditional adversarial networks, we embed adversarial learning under the umbrella of reinforcement learning. In this way, the response generation problem can be tackled by the generator taking a sequence of actions on selecting the proper word of each timestep for output. To justify our model, we construct a large-scale response generation dataset based on Twitter, consisting of 6,763 tweets with a corresponding 1,461,713 response created by 153,664 users. Extensive experiments demonstrate that CRobot surpasses the state-of-the-art baselines regarding both subjective and objective evaluation.