bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunosuppression therapy for idiopathic membranous nephropathy: systematic review with network meta-analysis
Authors: Bose Bhadran , Chung Edmund Y. M. , Hong Regina , Strippoli Giovanni F. M. , Johnson David W. , Yang Wen-ling , Badve Sunil V. , Palmer Suetonia C.
Published: February 2022

Background

Idiopathic membranous nephropathy is a common cause of nephrotic syndrome in adults. The Kidney Disease Improving Global Outcomes guidelines recommend rituximab or cyclophosphamide and steroids, or calcineurin inhibitor-based therapy. However, there have been few or no head-to-head comparisons of the relative efficacy and safety of different immunosuppression regimens. We conducted a network meta-analysis to evaluate the comparative efficacy and safety of available immunosuppression strategies compared to cyclophosphamide in adults with idiopathic membranous nephropathy.

Methods

We performed a systematic search of MEDLINE, Embase and CENTRAL for randomized controlled trials in the treatment of adults with idiopathic membranous nephropathy. The primary outcome was complete remission. Secondary outcomes were kidney failure, partial remission, estimated glomerular filtration rate, doubling of serum creatinine, proteinuria, serious adverse events, discontinuation of treatment, serious infection and bone marrow suppression.

Results

Cyclophosphamide had uncertain effects on inducing complete remission when compared to rituximab (OR 0.35, CI 0.10–1.24, low certainty evidence), mycophenolate mofetil (OR 1.81, CI 0.69–4.71, low certainty), calcineurin inhibitor (OR 1.26, CI 0.61–2.63, low certainty) or steroid monotherapy (OR 2.31, CI 0.62–8.52, low certainty). Cyclophosphamide had a higher probability of inducing complete remission when compared to calcineurin inhibitor plus rituximab (OR 4.45, CI 1.04–19.10, low certainty). Compared to other immunosuppression strategies, there was limited evidence that cyclophosphamide had different effects on other pre-specified outcomes.

Conclusions

The comparative effectiveness and safety of immunosuppression strategies compared to cyclophosphamide is uncertain in adults with idiopathic membranous nephropathy.

Graphical abstract
Turning mobile big data insights into public health responses in times of pandemics: Lessons learnt from the Democratic Republic of the Congo
Authors: Gueguen Chloe , Snel Nicolas , Mutonji Eric
Published: February 2022

In low-income countries like the Democratic Republic of the Congo (DRC)—where data is scarce and national statistics offices often under-resourced—aggregated and anonymised mobile operators’ data can provide vital insights for decision-makers to promptly respond to both prevailing and new pandemics, such as COVID-19. Yet, while research on possible applications of mobile big data (MBD) analytics for COVID-19 is growing, there is still little evidence on how such use cases are actually being adopted by governmental authorities and how MBD insights can effectively be turned into informed public health actions in times of crises. This four-part commentary paper aims to bridge such literature gaps, by sharing lessons learnt from the DRC, whereby Congolese public health authorities, through a steep learning curve, have initiated a public–private sector dialogue with local mobile network operators (MNOs) and their ecosystem partners to leverage population mobility insights for COVID-19 policy-making. After having set the scene on the policy relevance of MBD analytics in the context of the DRC in the first section, the paper will then detail four key enablers that contributed, since March 2020, to accelerate Congolese authorities’ uptake of MBD, thus effectively increasing preparedness for future pandemics. Thirdly, we showcase concreate use-cases where “readiness-to-use” has actually translated into actual “usage” and “adoption” for decision-making, while introducing other use cases currently under development. Finally, we explore challenges when harnessing telco big data for decision-making with the ultimate aim to share lessons to replicate the successes and steer the development of MBD for social good in other low-income countries.
The COVID-19 Church-Closure Cases and the Free Exercise of Religion
Authors: Storslee Mark
Published: February 2022

In a series of cases over the past year, the U.S. Supreme Court upheld then struck down COVID-19–related restrictions on worship in various states across the country. Those decisions clarified that, under the Free Exercise Clause, laws burdening religion aren't “generally applicable” when they treat religious conduct less favorably than comparable secular conduct. But they also relied on controversial claims that religious gatherings were comparable to places like grocery stores in their likelihood of spreading the virus. This article offers a different perspective. In addition to the rule about comparators, general applicability also contains a second rule. Where a law requires officials to consider the religious reasons for conduct as a precondition for regulating it, the law isn't generally applicable and ought to be subject to heightened scrutiny. The Court mostly passed over that requirement in the COVID-19 church-closure cases. But rightly understood, it may have provided an alternative path for resolving them—and one that didn't depend on controversial comparisons between churches and shopping centers. Instead, focusing on this second aspect of general applicability would have yielded a commonsense conclusion: where a law or policy grants favored treatment for activities it explicitly deems “essential,” “critical,” or “life-sustaining,” one of those things must be religion, absent compelling reason to the contrary. And understanding the rationale behind that conclusion provides important insights about the meaning of the Free Exercise Clause and several other issues at the heart of the First Amendment.
Collective Self-Determination, Territory and the Wet'suwet’en: What Justifies the Political Authority of Historic Indigenous Governments over Land and People?
Authors: Luoma Michael
Published: February 2022

This article examines the Wet'suwet’en people's struggle for territorial control over their traditional homeland from the normative perspective of collective self-determination. I focus on two interlocking philosophical questions that arise in examination of the case: the justification for a group's right to control territory and the justification for the right of political institutions and officials within those institutions to make and enforce law for the occupants of the territory. I argue that, pursuant to the collective self-determination theory of territorial rights, the legitimate representatives of the Wet'suwet’en people must reflect the people's shared will. After describing the traditional governance system of the Wet'suwet’en people, I argue that there is nothing in principle preventing the hereditary chiefs from reflecting the shared will of the Wet'suwet’en people (as I argue electoral democracy is not always necessary for collective self-determination). I illustrate several reasons why hereditary leaders could reflect the shared will of Wet'suwet’en people better than alternative political authorities, while demonstrating that the political authority of any Wet'suwet’en governance system depends upon the actual endorsement of Wet'suwet’en people themselves.
Prevalence of Dirofilaria repens in dogs living in deltaic coastal plain of the Volturno River (Italy): a geographical risk model of infection
Authors: Ferrara M. , Maglione R. , Ciccarelli D. , Mundis S.J. , Di Loria A. , Pisaroglo de Carvalho M. , Santoro D.
Published: February 2022

The prevalence of vector-associated parasitic infections is high in central-southern Italy. The deltaic coastal plain of the Volturno River has been suspected, by veterinary practitioners, to have a high accidental incidence of Dirofilaria repens. Thus, the goal of this study was to evaluate the prevalence of dirofilariasis and other coinfections frequently described in dogs living in the Volturno area. Blood samples of 100 clinical asymptomatic dogs were examined using a Knott's technique and polymerase chain reaction in order to identify microfilariae. Other vector-borne coinfections were also investigated using ELISA kits. The results were analysed using statistical and Geographic Information System (GIS) software. Microfilariae of D. repens were detected in 10% of the dogs surveyed, with a presence of antibodies against Ehrlichia canis (4/10) and Dirofilaria immitis (1/10). Such high incidence should be considered in light of the zoonotic potential for D. repens and the support for more regular use of repellents to prevent the spread of this disease. The GIS analyses indicated that the study area provides suitable conditions to sustain populations of mosquito vectors and D. repens parasites throughout much of the year.
A randomised controlled trial of acceptance and commitment therapy for improving quality of life in people with muscle diseases
Authors: Rose Michael , Graham Christopher D. , O'Connell Nicola , Vari Chiara , Edwards Victoria , Taylor Emma , McCracken Lance M. , Radunovic Aleksander , Rakowicz Wojtek , Norton Sam , Chalder Trudie
Published: February 2022

Abstract

Background

Chronic muscle diseases (MD) are progressive and cause wasting and weakness in muscles and are associated with reduced quality of life (QoL). The ACTMuS trial examined whether Acceptance and Commitment Therapy (ACT) as an adjunct to usual care improved QoL for such patients as compared to usual care alone.

Methods

This two-arm, randomised, multicentre, parallel design recruited 155 patients with MD (Hospital and Depression Scale ⩾ 8 for depression or ⩾ 8 for anxiety and Montreal Cognitive Assessment ⩾ 21/30). Participants were randomised, using random block sizes, to one of two groups: standard medical care (SMC) (n = 78) or to ACT in addition to SMC (n = 77), and were followed up to 9 weeks. The primary outcome was QoL, assessed by the Individualised Neuromuscular Quality of Life Questionnaire (INQoL), the average of five subscales, at 9-weeks. Trial registration was NCT02810028.

Results

138 people (89.0%) were followed up at 9-weeks. At all three time points, the adjusted group difference favoured the intervention group and was significant with moderate to large effect sizes. Secondary outcomes (mood, functional impairment, aspects of psychological flexibility) also showed significant differences between groups at week 9.

Conclusions

ACT in addition to usual care was effective in improving QoL and other psychological and social outcomes in patients with MD. A 6 month follow up will determine the extent to which gains are maintained.
The influence of the temporal characteristics of events on adults’ and children’s pronoun resolution
Authors: FRANCEY Gillian , CAIN Kate
Published: February 2022

We examined the influence of the lexical and grammatical aspect of events on pronoun resolution in adults (18 to 23 years, N = 46), adolescents (13 to 14 years, N=66) and children (7 to 11 years, N=192). Participants were presented with 64 two-sentence stimuli: the first sentence described events with two same gender protagonists; the second began with a personal pronoun and described a status that could be attributed to either protagonist. Participants recorded to whom the pronoun referred, in a booklet. For all groups, Subject resolutions were more likely for events (a) without endpoints relative to those with endpoints, and (b) described as ongoing rather than completed, but this latter influence was restricted to events with endpoints for adults and adolescents. The findings provide support for the Event Structure Hypothesis of pronoun resolution (Rohde, Kehler & Elman, 2006) and provide new insights into the development of pronoun resolution.
Cognitive predictors of language abilities in primary school children: A cascaded developmental view
Authors: ACHA Joana , AGIRREGOIKOA Ainhize , BARRETO-ZARZA Florencia , ARRANZ-FREIJO Enrique B.
Published: February 2022

This study investigated the longitudinal relationship between children’s domain-general cognitive constraints underlying phonological and sentence processing development in a big sample of typically developing children. 104 children were tested on non-linguistic processing speed, phonological skills (phonological short term memory, phonological knowledge, phonological working memory), and sentence processing abilities (sentence repetition and receptive grammar) in 1st grade (aged 6 to 6.5) and one year later. A cross-lagged structural equation model showed that non-linguistic processing speed was a concurrent predictor of phonological skills, and that phonology had a powerful effect on the child’s sentence processing abilities concurrently and longitudinally, providing clear evidence for the role of domain-general processes in the developmental pathway of language. These findings support a cascaded cognitive view of language development and pose important challenges for evaluation and intervention strategies in childhood.
Censoring the Muses: Opera and Creative Control in Nicholas's Russia (1825–1855)
Authors: Zavlunov Daniil
Published: February 2022

This article offers the first systematic investigation of the institution of opera censorship in Russia during the reign of Nicholas I. Drawing on new archival sources, it examines censorship legislation, the organisation of dramatic (i.e., theatre) censorship, the workings of its bureaucracy, censors’ reports and protocols and Nicholas's personal decrees on productions of specific operas, and printed and manuscript librettos. From these, it distils the patterns of state intervention in opera, revealing a remarkable fluidity – even capriciousness – of approaches. Decisions to ban or permit, and specific intrusions into the texts, were based on the censors’ adherence to or disregard for the Empire's censorship laws, Nicholas's inclinations and impulses, changes in cultural policy, practical needs of the Imperial Theatres, the shifting political climate at home and abroad, and, most of all, the national point of origin of the operatic work under review. In addition to surveying the trends, the article offers three case studies: Glinka'sZhizn’ za Tsarya(A Life for the Tsar), Verdi'sRigolettoand Meyerbeer'sLes Huguenots.
Paediatric acute care cardiology collaborative data registry validation
Authors: Khadr L. , Hart S.A. , Schachtner S. , Graupe M. , Veneziale K.L. , Bushnell J. , Roberts F. , Jolly-Passerini H. , Madsen N.
Published: February 2022

Background:

The Pediatric Acute Care Cardiology Collaborative (PAC3) was established to improve acute care cardiology outcomes through the development of an accurate and well-validated clinical registry. We report the validation results of the initial PAC3 registry audits and describe a novel regional audit format developed to accommodate a rapidly expanding membership facilitate collaborative learning and allow for necessary modification due to the COVID-19 pandemic.

Materials and methods:

Six hospitals were audited using a regional audit format and three hospitals were subsequently audited virtually. Critical and challenging-to-collect data elements were audited among at least 40 randomly selected cases. Discrepancies were categorised as either major or minor depending on their relative importance to patient outcomes and clinical care. Results were tabulated and reported.

Results:

We audited 386 encounters and 27,086 individual data fields across 9 hospitals. The aggregate overall accuracy rate was 99.27% and the aggregate major discrepancy rate was 0.51%. The overall accuracy rate ranged from 98.77% to 99.59%, and the major discrepancy rate ranged from 0.26% to 0.88% across the cohort. No appreciable difference was seen between audit formats. Both the regional and virtual audit methods were viewed favourably by participants.

Conclusions:

A low data discrepancy rate was found demonstrating that the PAC3 registry is a highly accurate data source for use in quality improvement, benchmarking, and research. Regional audits and virtual audits were both successfully implemented.
Cryptogenic stroke caused by patent foramen ovale with thrombophilia and accessory tricuspid valve in a teenager
Authors: Takafuji Hiroya , Kato Nahoko , Obunai Kotaro
Published: February 2022

Accessory tricuspid valve is rare congenital abnormality. We describe a case of cryptogenic stroke in teenager boy caused by patent foramen ovale with thrombophilia and accessory tricuspid valve.
Aggregate Semantics for Propositional Answer Set Programs
Authors: ALVIANO MARIO , FABER WOLFGANG , GEBSER MARTIN
Published: February 2022

Answer set programming (ASP) emerged in the late 1990s as a paradigm for knowledge representation and reasoning. The attractiveness of ASP builds on an expressive high-level modeling language along with the availability of powerful off-the-shelf solving systems. While the utility of incorporating aggregate expressions in the modeling language has been realized almost simultaneously with the inception of the first ASP solving systems, a general semantics of aggregates and its efficient implementation have been long-standing challenges. Aggregates have been proposed and widely used in database systems, and also in the deductive database language Datalog, which is one of the main precursors of ASP. The use of aggregates was, however, still restricted in Datalog (by either disallowing recursion or only allowing monotone aggregates), while several ways to integrate unrestricted aggregates evolved in the context of ASP. In this survey, we pick up at this point of development by presenting and comparing the main aggregate semantics that have been proposed for propositional ASP programs. We highlight crucial properties such as computational complexity and expressive power, and outline the capabilities and limitations of different approaches by illustrative examples.
A SIMPLE SEQUENT SYSTEM FOR MINIMALLY INCONSISTENT LP
Authors: GOLAN REA
Published: February 2022

Minimally inconsistent LP (MiLP) is a nonmonotonic paraconsistent logic based on Graham Priest’s logic of paradox (LP). Unlike LP, MiLP purports to recover, in consistent situations, all of classical reasoning. The present paper conducts a proof-theoretic analysis of MiLP. I highlight certain properties of this logic, introduce a simple sequent system for it, and establish soundness and completeness results. In addition, I show how to use my proof system in response to a criticism of this logic put forward by J. C. Beall.
Die Neuordnung der psychotherapeutischen Weiterbildung
Authors: Werheid Katja
Published: February 2022

Zusammenfassung: Die Reform des Psychotherapeutengesetzes, dessen Neufassung im September 2020 in Kraft getreten ist, hat eine Reihe von Auswirkungen, die die künftige Weiterbildung in Neuropsychologischer Psychotherapie betreffen. In diesem Artikel werden der aktuelle Stand des komplexen Transitionsprozesses, die besondere Stellung des Fachgebiets Klinische Neuropsychologie in diesem Prozess sowie rechtlich-organisatorische Auswirkungen auf die künftige kammergeführte Weiterbildung dargestellt. Daraus abgeleitet werden zukünftige Aufgabenfelder für Akteure und Institutionen, die in verschiedenen Kontexten auf dem Gebiet der Klinischen Neuropsychologie tätig sind.
Neuropsychologische Psychotherapie an Universitäten
Authors: Billino Jutta , Hennig-Fast Kristina , Exner Cornelia
Published: February 2022

Zusammenfassung: Die Psychotherapieausbildungsreform hat die Weichen für eine Neupositionierung der Klinischen Neuropsychologie an den Universitäten gestellt. Durch die feste Verankerung der Neuropsychologie innerhalb der Psychotherapieaus- und weiterbildung ergeben sich neue Chancen für Forschung und Praxis. Allerdings besteht beim Aufbau der erforderlichen Infrastruktur an den meisten Standorten noch erheblicher Entwicklungsbedarf. Ziel muss sein, dem Gebiet der Neuropsychologischen Psychotherapie an den Universitäten ein Profil zu geben, das in Zukunft sowohl die klinische als auch wissenschaftliche Qualifizierung des Nachwuchses sichern kann.
Southern Ocean Precipitation Characteristics Observed From CloudSat and Ground Instrumentation During the Macquarie Island Cloud & Radiation Experiment (MICRE): April 2016 to March 2017
Authors: Tansey Emily , Marchand Roger , Protat Alain , Alexander Simon P. , Ding Saisai
Published: February 2022

A 1‐year blended surface precipitation data set using Parsivel disdrometer, surface W‐band radar, and tipping bucket measurements is produced for the Macquarie Island Cloud and Radiation Experiment (MICRE) and compared with retrievals from CloudSat (spaceborne 94 GHz radar). Surface precipitation was observed 44% ± 4% of the time between April 2016 and March 2017. Precipitation composed primarily of small particles (diameter <1 mm) occurred about 36% ± 2% of the time, constituting 10% of total accumulation. Remaining precipitation contained enough large particles such that the disdrometer could be used to identify the precipitation type as rain, ice, snow or wet snow. Seasonal and annual statistics on frequency of occurrence and accumulation for each precipitation type observed during MICRE are presented. Most ice and mixed phase precipitation was shallow, originating at a height of 3 km or lower, and occurred most often when Macquarie Island was to the northwest of the nearest cyclonic low‐pressure center. In contrast, rain was more often deep and occurred most frequently when the island was to the southeast of cyclonic lows. A weak diurnal cycle in frequency and mean rate was present with a minimum between 12:00 and 14:00 local time and maximum between 03:00 and 06:00 local time. The CloudSat 2C‐Precip‐Column product missed the lightest precipitation (because the near‐surface reflectivity is <−15 dBZ) and overestimated total liquid precipitation and occurrence of mixed phase precipitation, but captured reasonably well the distribution of rain rates for rates >0.5 mm/hr.
How to Work in the Dark on Deep Time
Authors: Goss Heather
Published: February 2022

Researchers who study the formation of Earth show how ingenuity can shed light on hidden moments of creation.
Gut microbiota and plasma cytokine levels in patients with attention-deficit/hyperactivity disorder
Authors: Wang Liang-Jen , Li Sung-Chou , Li Shiao-Wen , Kuo Ho-Chang , Lee Sheng-Yu , Huang Lien-Hung , Chin Chia-Yin , Yang Chia-Yu
Published: February 2022

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood mental disorder with undetermined pathophysiological mechanisms. The gut microbiota and immunological dysfunction may influence brain functions and social behaviours. In the current study, we aimed to explore the correlation of gut microbiome imbalance and inflammation in the pathophysiology of ADHD. Forty-one children with ADHD and thirty-nine healthy-control (HC) individuals were recruited. Faecal samples from all participants were collected and submitted for 16 S rRNA V3–V4 amplicon microbiome sequencing analysis. The plasma levels of 10 cytokines, including TNF-α, IL-6, IL-1β, IL-2, IL-10, IL-13, IL-17A, IFN-α2, IFN-γ, and MCP-1, were determined using a custom-made sandwich enzyme-linked immunosorbent assay (ELISA) developed by Luminex Flowmetrix. There was no significant difference between the ADHD and HC groups in species diversity in the faeces, as determined with α-diversity and β-diversity analysis. In the ADHD group, three differentially abundant taxonomic clades at the genus level were observed, namely Agathobacter, Anaerostipes, and Lachnospiraceae. Top differentially abundant bacteria and representative biological pathways were identified in children with ADHD using linear discriminant analysis (LDA) effect size (LEfSe), and the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis, respectively. The plasma levels of TNF-α were significantly lower in children with ADHD than in HCs. Within the ADHD group, the levels of TNF-α were negatively correlated with ADHD symptoms and diversity of the gut microbiome. Our study provides new insights into the association between gut microbiome dysbiosis and immune dysregulation, which may contribute to the pathophysiology of ADHD.
Psilocin acutely alters sleep-wake architecture and cortical brain activity in laboratory mice
Authors: Thomas Christopher W. , Blanco-Duque Cristina , Bréant Benjamin J. , Goodwin Guy M. , Sharp Trevor , Bannerman David M. , Vyazovskiy Vladyslav V.
Published: February 2022

Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A prominent factor associated with psychiatric disorders is disturbed sleep, and the sleep-wake cycle is implicated in the homeostatic regulation of neuronal activity and synaptic plasticity. However, it remains largely unknown to what extent psychedelic agents directly affect sleep, in terms of both acute arousal and homeostatic sleep regulation. Here, chronic electrophysiological recordings were obtained in mice to track sleep-wake architecture and cortical activity after psilocin injection. Administration of psilocin led to delayed REM sleep onset and reduced NREM sleep maintenance for up to approximately 3 h after dosing, and the acute EEG response was associated primarily with an enhanced oscillation around 4 Hz. No long-term changes in sleep-wake quantity were found. When combined with sleep deprivation, psilocin did not alter the dynamics of homeostatic sleep rebound during the subsequent recovery period, as reflected in both sleep amount and EEG slow-wave activity. However, psilocin decreased the recovery rate of sleep slow-wave activity following sleep deprivation in the local field potentials of electrodes targeting the medial prefrontal and surrounding cortex. It is concluded that psilocin affects both global vigilance state control and local sleep homeostasis, an effect which may be relevant for its antidepressant efficacy.
SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7
Authors: Zhang Zi-Mu , Cao Hai-Bo , Li Zhi-Heng , Zhuo Ran , Tao Yan-Fang , Li Xiao-Lu , Li Gen , Liao Xin-Mei , Fang Fang , Xie Yi , Wu Di , Wang Hai-Rong , Wang Jian-Wei , Chen Yan-Ling , Yu Juan-Juan , Jia Si-Qi , Yang Ran-Dong , Guo Xin-Yi , Yang Yang , Feng Chen-Xi , Xu Yun-Yun , Qian Guang-Hui , Pan Jian
Published: February 2022

Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB. SAPCD2 promoted NB progression in vitro and in vivo. Mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity. Among the E2F family members, the roles of E2F7 in NB are poorly understood. We found that an increasing level of nuclear E2F7 was induced by SAPCD2 knockdown, thereby affecting the expression of genes involved in the cell cycle and chromosome instability. In addition, Selinexor (KTP-330), a clinically available inhibitor of exportin 1 (XPO1), could induce nuclear accumulation of E2F7 and suppress the growth of NB. Overall, our studies suggested a previously unrecognized role of SAPCD2 in the E2F signaling pathway and a potential therapeutic approach for NB, as well as clues for understanding the differences in subcellular distribution of E2F1 and E2F7 during their nucleocytoplasmic shuttling.
Neutrophil extracellular traps promote metastasis in gastric cancer patients with postoperative abdominal infectious complications
Authors: Xia Xiang , Zhang Zizhen , Zhu Chunchao , Ni Bo , Wang Shuchang , Yang Shuofei , Yu Fengrong , Zhao Enhao , Li Qing , Zhao Gang
Published: February 2022

Postoperative abdominal infectious complication (AIC) is associated with metastasis in locally advanced gastric cancer (GC) patients after radical gastrectomy. However, the underlying mechanism remains unclear. Herein, we report that neutrophil extracellular traps (NETs), the DNA meshes released by neutrophils in response to infection, could promote GC cells proliferation, invasion, migration and epithelial–mesenchymal transition dependent on TGF-β signaling. Then we model nude mice with cecal puncture without ligation to simulate postoperative AIC and find that NETs in peripheral blood and ascites fluid facilitate GC cells extravasation and implantation into liver and peritoneum for proliferation and metastasis. Notably, TGF-β signaling inhibitor LY 2157299 could effectively impede liver and peritoneal metastasis but not concurrently aggravate sepsis in those AIC-bearing nude mice. These findings implicate that targeting downstream effectors of NETs such as TGF-β signaling might provide potential therapeutic prospect to reduce the risk of GC metastasis.
Proteomic profiling reveals CDK6 upregulation as a targetable resistance mechanism for lenalidomide in multiple myeloma
Authors: Ng Yuen Lam Dora , Ramberger Evelyn , Bohl Stephan R. , Dolnik Anna , Steinebach Christian , Conrad Theresia , Müller Sina , Popp Oliver , Kull Miriam , Haji Mohamed , Gütschow Michael , Döhner Hartmut , Walther Wolfgang , Keller Ulrich , Bullinger Lars , Mertins Philipp , Krönke Jan
Published: February 2022

The immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide are highly effective treatments for multiple myeloma. However, virtually all patients eventually relapse due to acquired drug resistance with resistance-causing genetic alterations being found only in a small subset of cases. To identify non-genetic mechanisms of drug resistance, we here perform integrated global quantitative tandem mass tag (TMT)-based proteomic and phosphoproteomic analyses and RNA sequencing in five paired pre-treatment and relapse samples from multiple myeloma patients. These analyses reveal a CDK6-governed protein resistance signature that includes myeloma high-risk factors such as TRIP13 and RRM1. Overexpression of CDK6 in multiple myeloma cell lines reduces sensitivity to IMiDs while CDK6 inhibition by palbociclib or CDK6 degradation by proteolysis targeting chimeras (PROTACs) is highly synergistic with IMiDs in vitro and in vivo. This work identifies CDK6 upregulation as a druggable target in IMiD-resistant multiple myeloma and highlights the use of proteomic studies to uncover non-genetic resistance mechanisms in cancer.
Comparison of temperature and doping dependence of elastoresistivity near a putative nematic quantum critical point
Authors: Palmstrom J. C. , Walmsley P. , Straquadine J. A. W. , Sorensen M. E. , Hannahs S. T. , Burns D. H. , Fisher I. R.
Published: February 2022

Strong electronic nematic fluctuations have been discovered near optimal doping for several families of Fe-based superconductors, motivating the search for a possible link between these fluctuations, nematic quantum criticality, and high temperature superconductivity. Here we probe a key prediction of quantum criticality, namely power-law dependence of the associated nematic susceptibility as a function of composition and temperature approaching the compositionally tuned putative quantum critical point. To probe the ‘bare’ quantum critical point requires suppression of the superconducting state, which we achieve by using large magnetic fields, up to 45 T, while performing elastoresistivity measurements to follow the nematic susceptibility. We performed these measurements for the prototypical electron-doped pnictide, Ba(Fe1−xCox)2As2, over a dense comb of dopings. We find that close to the putative quantum critical point, the elastoresistivity appears to obey power-law behavior as a function of composition over almost a decade of variation in composition. Paradoxically, however, we also find that the temperature dependence for compositions close to the critical value cannot be described by a single power law.
Assembling covalent organic framework membranes with superior ion exchange capacity
Authors: Wang Xiaoyao , Shi Benbing , Yang Hao , Guan Jingyuan , Liang Xu , Fan Chunyang , You Xinda , Wang Yanan , Zhang Zhe , Wu Hong , Cheng Tao , Zhang Runnan , Jiang Zhongyi
Published: February 2022

Ionic covalent organic framework membranes (iCOFMs) hold great promise in ion conduction-relevant applications because the high content and monodispersed ionic groups could afford superior ion conduction. The key to push the upper limit of ion conductivity is to maximize the ion exchange capacity (IEC). Here, we explore iCOFMs with a superhigh ion exchange capacity of 4.6 mmol g−1, using a dual-activation interfacial polymerization strategy. Fukui function is employed as a descriptor of monomer reactivity. We use Brønsted acid to activate aldehyde monomers in organic phase and Brønsted base to activate ionic amine monomers in water phase. After the dual-activation, the reaction between aldehyde monomer and amine monomer at the water-organic interface is significantly accelerated, leading to iCOFMs with high crystallinity. The resultant iCOFMs display a prominent proton conductivity up to 0.66 S cm−1, holding great promise in ion transport and ionic separation applications.
Effect of HO-1-modified BMMSCs on immune function in liver transplantation
Authors: Li Peng , Zhang Yuyi , Li Qiongxia , Zhang Yubo
Published: February 2022

We examined whether haem oxygenase-1 (HO-1) could enhance the immunosuppressive effects of bone marrow mesenchymal stem cells (BMMSCs) on the rejection of transplanted liver allografts in rats. The animals were divided into three groups: the normal saline (NS) group, BMMSC group and HO-1/BMMSCs group. In vitro, the extraction, culture and HO-1 transfection of BMMSCs were performed. Mixed lymphocyte response (MLR) analysis of HO-1/BMMSCs efficacy was performed. The rejection model of orthotopic liver transplantation in rats was established when BMMSCs and HO-1/BMMSCs were transfused via the portal vein. To reduce research bias, we established an isogenic Liver transplantation model of (LEW → LEW) and (BN → BN), which can achieve tolerance. Changes in histopathology and liver function in the transplanted liver and changes in regulatory T cell (Tregs), natural killer (NK) cells and cytokines after transplantation were observed in the different groups. The severe acute rejection after liver transplantation on postoperative Day 10 was observed in the NS group. The BMMSC group showed strong protective effects against rejection within the first 10 days after transplantation, while HO-1/BMMSCs showed stronger effects on rejection than BMMSCs alone. In addition, the activity of natural killer (NK) cells decreased significantly, the levels of regulatory T cells (Tregs), interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) increased significantly and the levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23), tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) decreased significantly in the HO-1/BMMSC group compared with the BMMSC group. HO-1/BMMSCs showed better immunosuppressive effects after liver transplantation than the other treatments. Our findings reveal that HO-1 can enhance the effects of BMMSCs on inhibiting acute rejection in orthotopic liver transplantation in rats.
The fliR gene contributes to the virulence of S. marcescens in a Drosophila intestinal infection model
Authors: Sina Rahme Bechara , Lestradet Matthieu , Di Venanzio Gisela , Ayyaz Arshad , Yamba Miriam Wennida , Lazzaro Martina , Liégeois Samuel , Garcia Véscovi Eleonora , Ferrandon Dominique
Published: February 2022

Serratia marcescens is an opportunistic bacterium that infects a wide range of hosts including humans. It is a potent pathogen in a septic injury model of Drosophila melanogaster since a few bacteria directly injected in the body cavity kill the insect within a day. In contrast, flies do not succumb to ingested bacteria for days even though some bacteria cross the intestinal barrier into the hemolymph within hours. The mechanisms by which S. marcescens attacks enterocytes and damages the intestinal epithelium remain uncharacterized. To better understand intestinal infections, we performed a genetic screen for loss of virulence of ingested S. marcescens and identified FliR, a structural component of the flagellum, as a virulence factor. Next, we compared the virulence of two flagellum mutants fliR and flhD in two distinct S. marcescens strains. Both genes are required for S. marcescens to escape the gut lumen into the hemocoel, indicating that the flagellum plays an important role for the passage of bacteria through the intestinal barrier. Unexpectedly, fliR but not flhD is involved in S. marcescens-mediated damages of the intestinal epithelium that ultimately contribute to the demise of the host. Our results therefore suggest a flagellum-independent role for fliR in bacterial virulence.
Kinematics and kinetics comparison of ultra-congruent versus medial-pivot designs for total knee arthroplasty by multibody analysis
Authors: Putame Giovanni , Terzini Mara , Rivera Fabrizio , Kebbach Maeruan , Bader Rainer , Bignardi Cristina
Published: February 2022

Nowadays, several configurations of total knee arthroplasty (TKA) implants are commercially available whose designs resulted from clinical and biomechanical considerations. Previous research activities led to the development of the so-called medial-pivot (MP) design. However, the actual benefits of the MP, with respect to other prosthesis designs, are still not well understood. The present work compares the impact of two insert geometries, namely the ultra-congruent (UC) and medial-pivot (MP), on the biomechanical behaviour of a bicondylar total knee endoprosthesis. For this purpose, a multibody model of a lower limb was created alternatively integrating the two implants having the insert geometry discretized. Joint dynamics and contact pressure distributions were evaluated by simulating a squat motion. Results showed a similar tibial internal rotation range of about 3.5°, but an early rotation occurs for the MP design. Furthermore, the discretization of the insert geometry allowed to efficiently derive the contact pressure distributions, directly within the multibody simulation framework, reporting peak pressure values of 33 MPa and 20 MPa for the UC and MP, respectively. Clinically, the presented findings confirm the possibility, through a MP design, to achieve a more natural joint kinematics, consequently improving the post-operative patient satisfaction and potentially reducing the occurrence of phenomena leading to the insert loosening.
Risk factor targeting for vaccine prioritization during the COVID-19 pandemic
Authors: Chapman Lloyd A. C. , Shukla Poojan , Rodríguez-Barraquer Isabel , Shete Priya B. , León Tomás M. , Bibbins-Domingo Kirsten , Rutherford George W. , Schechter Robert , Lo Nathan C.
Published: February 2022

A key public health question during any disease outbreak when limited vaccine is available is who should be prioritized for early vaccination. Most vaccine prioritization analyses only consider variation in risk of infection and death by a single risk factor, such as age. We provide a more granular approach with stratification by demographics, risk factors, and location. We use this approach to compare the impact of different COVID-19 vaccine prioritization strategies on COVID-19 cases, deaths and disability-adjusted life years (DALYs) over the first 6 months of vaccine rollout, using California as a case example. We estimate the proportion of cases, deaths and DALYs averted relative to no vaccination for strategies prioritizing vaccination by a single risk factor and by multiple risk factors (e.g. age, location). When targeting by a single risk factor, we find that age-based targeting averts the most deaths (62% for 5 million individuals vaccinated) and DALYs (38%) and targeting essential workers averts the least deaths (31%) and DALYs (24%) over the first 6 months of rollout. However, targeting by two or more risk factors simultaneously averts up to 40% more DALYs. Our findings highlight the potential value of multiple-risk-factor targeting of vaccination against COVID-19 and other infectious diseases, but must be balanced with feasibility for policy.
Neural model generating klinotaxis behavior accompanied by a random walk based on C. elegans connectome
Authors: Chen Mohan , Feng Dazheng , Su Hongtao , Su Tingting , Wang Meng
Published: February 2022

Klinotaxis is a strategy of chemotaxis behavior inCaenorhabditis elegans(C. elegans), and random walking is evident during its locomotion. As yet, the understanding of the neural mechanisms underlying these behaviors has remained limited. In this study, we present a connectome-based simulation model ofC. elegansto concurrently realize realistic klinotaxis and random walk behaviors and explore their neural mechanisms. First, input to the model is derived from an ASE sensory neuron model in which the all-or-none depolarization characteristic of ASEL neuron is incorporated for the first time. Then, the neural network is evolved by an evolutionary algorithm; klinotaxis emerged spontaneously. We identify a plausible mechanism of klinotaxis in this model. Next, we propose the liquid synapse according to the stochastic nature of biological synapses and introduce it into the model. Adopting this, the random walk is generated autonomously by the neural network, providing a new hypothesis as to the neural mechanism underlying the random walk. Finally, simulated ablation results are fairly consistent with the biological conclusion, suggesting the similarity between our model and the biological network. Our study is a useful step forward in behavioral simulation and understanding the neural mechanisms of behaviors inC. elegans.
Percutaneous coronary intervention for chronic total occlusion in octogenarians: a propensity score study
Authors: Blessing Recha R. L. , Ahoopai Majid , Geyer Martin , Brandt Moritz , Zeiher Andreas M. , Vasa-Nicotera Mariuca , Münzel Thomas , Wenzel Philip , Gori Tommaso , Dimitriadis Zisis
Published: February 2022

Feasibility and efficacy of complex percutaneous coronary intervention (PCI) in the elderly, a more frail population due to more comorbidities is incompletely understood. We therefore set out to compare success and complication rate of PCI for chronic total occlusion (CTO) in octogenarians, in comparison to non-octogenarians. Data from 267 patients (58 patients over 80 years of age and 209 under 80 years of age) who had undergone CTO PCI were analyzed. To compare the results we calculated the propensity score and used inverse probability of treatment weighting. We evaluated demographic, clinical, angiographic, and periprocedural information. The median age of the total collective was 68 (31–90) years (octogenarian collective 82 (80–90) years vs non-octogenarians 65 (31–79) years). We observed a high success rate in both collectives (82.8% vs 90.4%, p = 0.10) and no difference in periprocedural complications or complications in the follow-up period. In our collective restenosis rate at follow-up was comparable to the propensity sore weighted population (11.3% vs 16.3%, p = 0.9). Our results show that CTO PCI in older patients is safe and feasible with comparable in-hospital and follow-up complication rates compared to a younger patient population.
Vertical oxide thin-film transistor with interfacial oxidation
Authors: Baek Yeong Jo , Kang In Hye , Hwang Sang Ho , Han Ye Lin , Kang Min Su , Kang Seok Jun , Kim Seo Gwon , Woo Jae Geun , Yu Eun Seong , Bae Byung Seong
Published: February 2022

A vertical oxide thin-film transistor was developed with interfacial oxidation for low voltage operation. The gate metal was used as a spacer for the definition of the transistor’s channel as well as the gate electrode. After definition of the vertical side wall, an IGZO (In-Ga-Zn Oxide) layer was deposited, followed by the interfacial oxidation to form a thin gate insulator. Ta was used for the gate material due to the low Gibbs free energy and high dielectric constant of tantalum oxide. A 15 nm tantalum oxide layer was obtained by the interfacial oxidation of Ta at 400 °C under oxygen atmosphere. The thin gate oxide made it possible to operate the transistor under 1 V. The low operation voltage enables low power consumption, which is essential for mobile application.
A multi-sensory stimulating attention model for cities’ taxi service demand prediction
Authors: Liao Lyuchao , Wang Yongqiang , Zou Fumin , Bi Shuoben , Su Jinya , Sun Qi
Published: February 2022

Taxi demand forecasting is crucial to building an efficient transportation system in a smart city. Accurate taxi demand forecasting could help the taxi management platform to allocate taxi resources in advance, alleviate traffic congestion, and reduce passenger waiting time. Thus, more efforts in industrial and academic circles have been directed towards the cities’ taxi service demand prediction (CTSDP). However, the complex nonlinear spatio-temporal relationship in demand data makes it challenging to construct an accurate forecasting model. There remain challenges in perceiving the micro spatial characteristics and the macro periodicity characteristics from cities’ taxi service demand data. What’s more, the existing methods are significantly insufficient for exploring the potential multi-time patterns from these demand data. To meet the above challenges, and also stimulated by the human perception mechanism, we propose a Multi-Sensory Stimulus Attention (MSSA) model for CTSDP. Specifically, the MSSA model integrates a detail perception attention and a stimulus variety attention for capturing the micro and macro characteristics from massive historical demand data, respectively. The multiple time resolution modules are employed to capture multiple potential spatio-temporal periodic features from massive historical demand data. Extensive experiments on the yellow taxi trip records data in Manhattan show that the MSSA model outperforms the state-of-the-art baselines.
Mitochondrial dysfunction associated with TANGO2 deficiency
Authors: Heiman Paige , Mohsen Al-Walid , Karunanidhi Anuradha , St Croix Claudette , Watkins Simon , Koppes Erik , Haas Richard , Vockley Jerry , Ghaloul-Gonzalez Lina
Published: February 2022

Transport and Golgi Organization protein 2 Homolog (TANGO2)-related disease is an autosomal recessive disorder caused by mutations in the TANGO2 gene. Symptoms typically manifest in early childhood and include developmental delay, stress-induced episodic rhabdomyolysis, and cardiac arrhythmias, along with severe metabolic crises including hypoglycemia, lactic acidosis, and hyperammonemia. Severity varies among and within families. Previous studies have reported contradictory evidence of mitochondrial dysfunction. Since the clinical symptoms and metabolic abnormalities are suggestive of a broad dysfunction of mitochondrial energy metabolism, we undertook a broad examination of mitochondrial bioenergetics in TANGO2 deficient patients utilizing skin fibroblasts derived from three patients exhibiting TANGO2-related disease. Functional studies revealed that TANGO2 protein was present in mitochondrial extracts of control cells but not patient cells. Superoxide production was increased in patient cells, while oxygen consumption rate, particularly under stress, along with relative ATP levels and β-oxidation of oleate were reduced. Our findings suggest that mitochondrial function should be assessed and monitored in all patients with TANGO2 mutation as targeted treatment of the energy dysfunction could improve outcome in this condition.