bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of preventive use of hydrolyzed protein formula milk on gastrointestinal diseases and physical development of premature infants
Authors: Yang Qiyan , Lin Qun , Chen Keni , Cao Juan , Feng Yonghong , Han Shuli
Published: November 2020

Background:

Because of the controversy in clinical nutritional support therapy of hydrolyzed protein formula milk and standard preterm infant formula (SPIF) in premature infants. In this study, the effectiveness and safety of preventive use of hydrolyzed protein formula milk in reducing gastrointestinal diseases and promoting physical development of premature infants are scientifically evaluated by systematic evaluation. To help find the suitable nutritional support for premature infants.

Methods:

To search the database of Chinese and English by computer: SinoMed, CNKI, WanFang Data, VIP, PubMed, EMbase and The Cochrane Library, and to collect randomized controlled trials on the application of hydrolyzed protein formula milk in nutritional support treatment of premature infants compared with SPIF. The retrieval time limit is from the establishment of each database to September 1, 2020. Two authors independently completed the paper search, and sorting out the main outcome indicator and secondary outcome indicator in the selected literature, and the data are statistically analyzed by Review Manager software (RevManV.5.3.0) and STATA 13.0.

Results:

This study will provide a high-quality evidence on the effects of hydrolyzed protein formula milk on gastrointestinal diseases and physical development of premature infants.

Conclusion:

At present, the clinicians are controversial about the safety and effectiveness of hydrolyzed protein formula milk and SPIF in the nutritional support therapy of premature infants. This study will compare the effectiveness and safety of these 2 nutritional support methods, and make a comprehensive analysis of the influence of hydrolyzed protein formula milk on gastrointestinal diseases and physical development of premature infants, and finally give a positive conclusion.

OSF registration number:

DOI 10.17605/OSF.IO/UQD92
Effect of initiation of renal replacement therapy on mortality in acute pancreatitis patients
Authors: Zhang Xing , Cao Yang , Pan Chang-Kun , Han Qiu-Yuan , Guo Ya-Qi , Song Ting , Qi Zhi-Dong , Huang Rui , Li Ming , Yang Zhen-Yu , Zheng Jun-Bo , Hou Gui-Ying , Li Jia-Yu , Wang Si-Cong , Liu Yan-Song , Liu Rui-Jin , Gao Yang , Wang Hong-Liang
Published: November 2020

This study aims to explore effect of initiation of renal replacement therapy (RRT) on mortality in acute pancreatitis (AP) patients. In this study, a total of 92 patients from the surgical intensive care unit (SICU) of the Second Affiliated Hospital of Harbin Medical University who were diagnosed with AP and underwent RRT or not between January 2014 and December 2018 were included in this retrospective study. Demographic and clinical data were obtained on admission to SICU. Patients were divided into early initiation of RRT group (n = 44) and delayed initiation of RRT group (n = 48). Duration of mechanical ventilation (MV), intra-peritoneal pressure, vasopressors infusion, body temperature, procalcitonin, creatinine, platelet counts, length of hospital stay and prognosis were recorded during hospitalization, and then compared between groups. Patients with delayed initiation of RRT exhibited significantly higher APACHE II score, SOFA score and lower GCS score than those with early initiation of RRT (P < 0.001, <0.001,  = 0.04, respectively). No difference in the rest of the baseline data and vasopressors infusion was found. Dose of Norepinephrine, maximum and mean PCT, maximum and mean creatinine, maximum and mean intra-peritoneal pressure, length of hospital stay, prognosis of ICU and hospitalization showed significant difference between groups. Early initiation of RRT may be beneficial for AP patients, which can provide some insight and support for patients’ treatment in clinic.
Clinical characteristics of non-ampullary duodenal polyps in the elderly and the outcomes of endoscopic mucosal resection
Authors: Zheng Linfu , Li Dazhou , Jiang Chuanshen , Zhang Xiaolan , Wang Rong , Zeng Xiangpeng , Zheng Yunping , Chen Junguo , Qiu Jianting , Zeng Dehua , Wang Wen
Published: November 2020

At present, there are no reports on non-ampullary polyps of the duodenum (NAPDs) in the elderly. The aim of this study was to analyze the clinicopathological features of NAPDs in elderly and non-elderly patients to explore the efficacy and safety of endoscopic mucosal resection (EMR) of NAPDs in the elderly.

A total of 110 patients underwent EMR of NAPDs between April 2016 and December 2019. The shape, location, size, postoperative complications, and histopathological types of NAPDs were compared between the elderly group (n = 44) and the non-elderly group (n = 66).

Sessile type was the most common form of NAPD in both groups. In the elderly group, the average size of NAPDs was 12.6 ± 3.9 mm. In the non-elderly group, NAPDs had an average size of 10.1 ± 5.8 mm. Complete EMR was performed in both groups. The postoperative complications of EMR did not significantly differ between the 2 groups. Postoperative pathological examination showed that tubular villous adenomas were more common in the elderly group than in the non-elderly group (P = .005), while tubular adenomas were more common in the non-elderly group than in the elderly group (P = .007). Of the 110 patients, 99 completed postoperative follow-up (median follow-up duration, 20.93 months). There were no residual or recurrent lesions.

EMR is safe and effective for the treatment of NAPDs in elderly patients.
Neutrophil Phenotypes and Functions in Trauma and Trauma-Related Sepsis
Authors: Janicova Andrea , Relja Borna
Published: November 2020

Physical trauma is one of the leading causes of mortality worldwide. Early post-traumatic upregulation of the pro-inflammatory immune response to traumatic injury is paralleled by an anti-inflammatory reaction. A prevalence of each has been associated with the development of secondary complications, including nosocomial infections, acute lung injury, acute respiratory distress syndrome, sepsis, and death after trauma. There is accumulating evidence that neutrophils, which are known to provide the first line of defense against invading pathogens or harmful agents, are considerably involved in the initiation and propagation of the inflammatory response to traumatic injury. In this review, we summarize and discuss recent findings about the impact of trauma and trauma-related sepsis as a secondary complication on neutrophil biology, which constitutes as the interface between homeostasis and tissue damage after a traumatic insult. Here, patient cohorts of physically injured patients with an overall injury severity score above 9 have been considered, including patients with blunt as well as penetrating injuries, and sepsis. Mechanisms were replenished by animal studies. Altered antigen presentation on neutrophils has been shown to possess biomarker features predicting both outcome and vulnerability to infectious complications in severely injured patients. Dysregulated activation of neutrophils following trauma affects their functions including phagocytizing capacity, production of reactive oxygen species, formation of neutrophil extracellular traps, which all together have been associated with the development of secondary complications. Thus, we highlight neutrophils and their functions as potential future targets for optimizing post-traumatic treatment strategies, which potentially may improve patient outcomes.
Condition-dependent responses of fish to motorboats
Authors: Harding H. R. , Gordon T. A. C. , Wong K. , McCormick M. I. , Simpson S. D. , Radford A. N.
Published: November 2020

Anthropogenic noise is a pollutant of global concern that has been shown to have a wide range of detrimental effects on multiple taxa. However, most noise studies to-date consider only overall population means, ignoring the potential for intraspecific variation in responses. Here, we used field experiments on Australia's Great Barrier Reef to assess condition-dependent responses of blue-green damselfish (Chromis viridis) to real motorboats. Despite finding no effect of motorboats on a physiological measure (opercular beat rate; OBR), we found a condition-dependent effect on anti-predator behaviour. In ambient conditions, startle responses to a looming stimulus were equivalent for relatively poor- and good-condition fish, but when motorboats were passing, poorer-condition fish startled at significantly shorter distances to the looming stimulus than better-condition fish. This greater susceptibility to motorboats in poorer-condition fish may be the result of generally more elevated stress levels, as poorer-condition fish had a higher pre-testing OBR than those in better condition. Considering intraspecific variation in responses is important to avoid misrepresenting potential effects of anthropogenic noise and to ensure the best management and mitigation of this pervasive pollutant.
Can paternal effects via seminal fluid contribute to the evolution of polyandry?
Authors: Simmons Leigh W. , Lovegrove Maxine
Published: November 2020

Genetic benefits from mating with multiple males are thought to favour the evolution of polyandry. However, recent evidence suggests that non-genetic paternal effects via seminal fluid might contribute to the observed effects of polyandry on offspring performance. Here, we test this hypothesis using the field cricket
Teleogryllus oceanicus
. Using interference RNA, we first show that at least one seminal fluid protein is essential for embryo survival. We then show that polyandrous females mated to three different males produced embryos with higher pre-hatching viability than did monandrous females mated with the same male three times. Pseudo-polyandrous females that obtained sperm and seminal fluid from a single male and seminal fluid from two additional males had embryos with viabilities intermediate between monandrous and polyandrous females. Our results suggest either that ejaculate mediated paternal effects on embryo viability have both genetic and non-genetic components, or that seminal fluids transferred by castrated males provide only a subset of proteins contained within the normal ejaculate, and are unable to exert their full effect on embryo viability.
Learning enables adaptation in cooperation for multi-player stochastic games
Authors: Huang Feng , Cao Ming , Wang Long
Published: November 2020

Interactions among individuals in natural populations often occur in a dynamically changing environment. Understanding the role of environmental variation in population dynamics has long been a central topic in theoretical ecology and population biology. However, the key question of how individuals, in the middle of challenging social dilemmas (e.g. the ‘tragedy of the commons’), modulate their behaviours to adapt to the fluctuation of the environment has not yet been addressed satisfactorily. Using evolutionary game theory, we develop a framework of stochastic games that incorporates the adaptive mechanism of reinforcement learning to investigate whether cooperative behaviours can evolve in the ever-changing group interaction environment. When the action choices of players are just slightly influenced by past reinforcements, we construct an analytical condition to determine whether cooperation can be favoured over defection. Intuitively, this condition reveals why and how the environment can mediate cooperative dilemmas. Under our model architecture, we also compare this learning mechanism with two non-learning decision rules, and we find that learning significantly improves the propensity for cooperation in weak social dilemmas, and, in sharp contrast, hinders cooperation in strong social dilemmas. Our results suggest that in complex social–ecological dilemmas, learning enables the adaptation of individuals to varying environments.
The effect of social balance on social fragmentation
Authors: Minh Pham Tuan , Kondor Imre , Hanel Rudolf , Thurner Stefan
Published: November 2020

With the availability of internet, social media, etc., the interconnectedness of people within most societies has increased tremendously over the past decades. Across the same timespan, an increasing level of fragmentation of society into small isolated groups has been observed. With a simple model of a society, in which the dynamics of individual opinion formation is integrated with social balance, we show that these two phenomena might be tightly related. We identify a critical level of interconnectedness, above which society fragments into sub-communities that are internally cohesive and hostile towards other groups. This critical communication density necessarily exists in the presence of social balance, and arises from the underlying mathematical structure of a phase transition known from the theory of disordered magnets called spin glasses. We discuss the consequences of this phase transition for social fragmentation in society.
Viral macrodomains: a structural and evolutionary assessment of the pharmacological potential
Authors: Rack Johannes Gregor Matthias , Zorzini Valentina , Zhu Zihan , Schuller Marion , Ahel Dragana , Ahel Ivan
Published: November 2020

Viral macrodomains possess the ability to counteract host ADP-ribosylation, a post-translational modification implicated in the creation of an antiviral environment via immune response regulation. This brought them into focus as promising therapeutic targets, albeit the close homology to some of the human macrodomains raised concerns regarding potential cross-reactivity and adverse effects for the host. Here, we evaluate the structure and function of the macrodomain of SARS-CoV-2, the causative agent of COVID-19. We show that it can antagonize ADP-ribosylation by PARP14, a cellular (ADP-ribosyl)transferase necessary for the restriction of coronaviral infections. Furthermore, our structural studies together with ligand modelling revealed the structural basis for poly(ADP-ribose) binding and hydrolysis, an emerging new aspect of viral macrodomain biology. These new insights were used in an extensive evolutionary analysis aimed at evaluating the druggability of viral macrodomains not only from theCoronaviridaebut alsoTogaviridaeandIridoviridaegenera (causing diseases such as Chikungunya and infectious spleen and kidney necrosis virus disease, respectively). We found that they contain conserved features, distinct from their human counterparts, which may be exploited during drug design.
Biochemical evidence for diverse strategies in the inner kinetochore
Authors: Hamilton G. E. , Davis T. N.
Published: November 2020

The kinetochore is a complex structure whose function is absolutely essential. Unlike the centromere, the kinetochore at first appeared remarkably well conserved from yeast to humans, especially the microtubule-binding outer kinetochore. However, recent efforts towards biochemical reconstitution of diverse kinetochores challenge the notion of a similarly conserved architecture for the constitutively centromere-associated network of the inner kinetochore. This review briefly summarizes the evidence from comparative genomics for interspecific variability in inner kinetochore composition and focuses on novel biochemical evidence indicating that even homologous inner kinetochore protein complexes are put to different uses in different organisms.
A versatile Diels–Alder approach to functionalized hydroanthraquinones
Authors: Beck Janina , Fuhr Olaf , Nieger Martin , Bräse Stefan
Published: November 2020

The synthesis of highly substituted hydroanthraquinone derivatives with up to three stereogenic centres
via
a Diels–Alder reaction, starting from easily accessible 2-substituted naphthoquinones, is described. The [4+2]-cycloaddition is applicable for a broad range of substrates, runs under mild conditions and results in high yields. The highly regioselective outcome of the reactions is enabled by a benzoyl substituent at C2 of the dienophiles. The obtained hydroanthraquinones can be further modified and represent ideal substrates for follow-up intramolecular coupling reactions to create unique bicyclo[3.3.1] or -[3.2.2]nonane ring systems which are important natural product skeletons.
Robust estimates of the true (population) infection rate for COVID-19: a backcasting approach
Authors: Phipps Steven J. , Grafton R. Quentin , Kompas Tom
Published: November 2020

Differences in COVID-19 testing and tracing across countries, as well as changes in testing within each country over time, make it difficult to estimate the true (population) infection rate based on the confirmed number of cases obtained through RNA viral testing. We applied a backcasting approach to estimate a distribution for the true (population) cumulative number of infections (infected and recovered) for 15 developed countries. Our sample comprised countries with similar levels of medical care and with populations that have similar age distributions. Monte Carlo methods were used to robustly sample parameter uncertainty. We found a strong and statistically significant negative relationship between the proportion of the population who test positive and the implied true detection rate. Despite an overall improvement in detection rates as the pandemic has progressed, our estimates showed that, as at 31 August 2020, the true number of people to have been infected across our sample of 15 countries was 6.2 (95% CI: 4.3–10.9) times greater than the reported number of cases. In individual countries, the true number of cases exceeded the reported figure by factors that range from 2.6 (95% CI: 1.8–4.5) for South Korea to 17.5 (95% CI: 12.2–30.7) for Italy.
Interpreting the socio-technical interactions within a wind damage–artificial neural network model for community resilience
Authors: Pilkington Stephanie F. , Mahmoud Hussam N.
Published: November 2020

The use of machine learning has grown in popularity in various disciplines. Despite the popularity, the apparent ‘black box’ nature of such tools continues to be an area of concern. In this article, we attempt to unravel the complexity of this black box by exploring the use of artificial neural networks (ANNs), coupled with graph theory, to model and interpret the spatial distribution of building damage from extreme wind events at a community level. Structural wind damage is a topic that is mostly well understood for how wind pressure translates to extreme loading on a structure, how debris can affect that loading and how specific social characteristics contribute to the overall population vulnerability. While these themes are widely accepted, they have proven difficult to model in a cohesive manner, which has led primarily to physical damage models considering wind loading only as it relates to structural capacity. We take advantage of this modelling difficulty to reflect on two different ANN models for predicting the spatial distribution of structural damage due to wind loading. Through graph theory analysis, we study the internal patterns of the apparent black box of artificial intelligence of the models and show that social parameters are key to predict structural damage.
Migratory insights from singing humpback whales recorded around central New Zealand
Authors: Warren Victoria E. , Constantine Rochelle , Noad Michael , Garrigue Claire , Garland Ellen C.
Published: November 2020

The migration routes of wide-ranging species can be difficult to study, particularly at sea. In the western South Pacific, migratory routes of humpback whales between breeding and feeding areas are unclear. Male humpback whales sing a population-specific song, which can be used to match singers on migration to a breeding population. To investigate migratory routes and breeding area connections, passive acoustic recorders were deployed in the central New Zealand migratory corridor (2016); recorded humpback whale song was compared to song from the closest breeding populations of East Australia and New Caledonia (2015–2017). Singing northbound whales migrated past New Zealand from June to August via the east coast of the South Island and Cook Strait. Few song detections were made along the east coast of the North Island. New Zealand song matched New Caledonia song, suggesting a migratory destination, but connectivity to East Australia could not be ruled out. Two song types were present in New Zealand, illustrating the potential for easterly song transmission from East Australia to New Caledonia in this shared migratory corridor. This study enhances our understanding of western South Pacific humpback whale breeding population connectivity, and provides novel insights into the dynamic transmission of song culture.
RE
BCO mixtures with large difference in rare-earth ion size: superconducting properties of chemical solution deposition-grown Yb

1−
x

Sm

x

Ba
2
Cu
3
O
7−

δ

films
Authors: Cayado Pablo , Li Minjuan , Erbe Manuela , Liu Zhiyong , Cai Chuanbing , Hänisch Jens , Holzapfel Bernhard
Published: November 2020

The main objective of this work was to study the superconducting properties of
RE
BCO films with a mixture of rare-earth (
RE
) ions with large difference in ion size, in particular Sm
3+
and Yb
3+
. These Yb

1−
x

Sm

x

Ba
2
Cu
3
O
7−

δ

films have been successfully prepared for the first time by chemical solution deposition following the extremely low-fluorine route, which allows reducing the fluorine content by 93% with respect to standard full trifluoroacetate solutions. On the one hand, critical temperature
T
c
remains stable at approximately 90 K with Sm content up to
x
= 0.5 where
T
c
starts to increase towards the values of pure SmBCO films of approximately 95 K. On the other hand, the critical current densities
J
c
of the pure SmBCO films are the largest at 77 K, where the influence of a higher
T
c
is very relevant, while at lower temperatures and low fields, the mixed films reach larger values. This demonstrates that mixing rare-earth elements
RE
in
RE
Ba
2
Cu
3
O
7−

δ

causes a change in the pinning properties of the films and reveals the importance of selecting adequate
RE
BCO compounds according to the temperature and magnetic field region of a desired application.
Replicator–mutator dynamics of linguistic convergence and divergence
Authors: Kauhanen Henri
Published: November 2020

People tend to align their use of language to the linguistic behaviour of their own ingroup and to simultaneously diverge from the language use of outgroups. This paper proposes to model this phenomenon of sociolinguistic identity maintenance as an evolutionary game in which individuals play the field and the dynamics are supplied by a multi-population extension of the replicator–mutator equation. Using linearization, the stabilities of all dynamic equilibria of the game in its fully symmetric two-population special case are found. The model is then applied to an empirical test case from adolescent sociolinguistic behaviour. It is found that the empirically attested population state corresponds to one of a number of stable equilibria of the game under an independently plausible value of a parameter controlling the rate of linguistic mutations. An asymmetric three-population extension of the game, explored with numerical solution methods, furthermore predicts to which specific equilibrium the system converges.
Indirect reduced-order modelling: using nonlinear manifolds to conserve kinetic energy
Authors: Nicolaidou Evangelia , Hill Thomas L. , Neild Simon A.
Published: November 2020

Nonlinear dynamic analysis of complex engineering structures modelled using commercial finite element (FE) software is computationally expensive. Indirect reduced-order modelling strategies alleviate this cost by constructing low-dimensional models using a static solution dataset from the FE model. The applicability of such methods is typically limited to structures in which (a) the main source of nonlinearity is the quasi-static coupling between transverse and in-plane modes (i.e. membrane stretching); and (b) the amount of in-plane displacement is limited. We show that the second requirement arises from the fact that, in existing methods, in-plane kinetic energy is assumed to be negligible. For structures such as thin plates and slender beams with fixed/pinned boundary conditions, this is often reasonable, but in structures with free boundary conditions (e.g. cantilever beams), this assumption is violated. Here, we exploit the concept of nonlinear manifolds to show how the in-plane kinetic energy can be accounted for in the reduced dynamics, without requiring any additional information from the FE model. This new insight enables indirect reduction methods to be applied to a far wider range of structures while maintaining accuracy to higher deflection amplitudes. The accuracy of the proposed method is validated using an FE model of a cantilever beam.
Perturbation theory for Bose–Einstein condensates on bounded space domains
Authors: Van Gorder Robert A.
Published: November 2020

Bose–Einstein condensates (BECs), first predicted theoretically by Bose and Einstein and finally discovered experimentally in the 1990s, continue to motivate theoretical and experimental physics work. Although experiments on BECs are carried out in bounded space domains, theoretical work in the modelling of BECs often involves solving the Gross–Pitaevskii equation on unbounded domains, as the combination of bounded domains and spatial heterogeneity render most existing analytical approaches ineffective. Motivated by a lack of theory for BECs on bounded domains, we first derive a perturbation theory for both ground and excited stationary states on a given bounded space domain, allowing us to explore the role various forms of the self-interaction, external potential and space domain have on BECs. We are able to show that the shape and curvature of a space domain strongly influence BEC structure, and may be used as control mechanisms in experiments. We next derive a non-autonomous perturbation theory to predict BEC response to temporal changes in an external potential. In certain cases, our approach can be extended to unbounded domains, and we conclude by constructing a perturbation theory for bright solitons within external potentials on unbounded domains.
Molecular basis of bile-salt- and iron-induced enterohaemorrhagic E. coli resistance to cationic antimicrobial peptides
Authors: Kunwar Chhatra B. , Birstonas Sarah , McPhee Joseph B. , Barnett Foster Debora
Published: November 2020

Colonization of the gastrointestinal tract by enterohaemorrhagic

Escherichia coli

(EHEC) is critically dependent on its ability to sense and respond to various microenvironments within the host. EHEC exposure to physiologically relevant levels of bile salts upregulates the two-component system, pmrAB, and the arnBCADTEF operon, resulting in lipopolysaccharide modification and increased resistance to the cationic antimicrobial peptide, polymyxin B (PMB). A similar pmrAB- and arn-dependent PMB resistance has been observed in

Salmonella enterica

in the presence of ferric iron. Limiting magnesium levels and mild acid can also induce

Salmonella

resistance to PMB through another two-component system, PhoPQ and the connector protein, PmrD. This study aims to evaluate the relative contributions of a bile-salt mix (BSM), iron, limiting magnesium as well as the roles of pmrAB, phoPQ and pmrD to EHEC’s resistance to PMB. Killing assays show that EHEC treatment with the BSM or iron under excess magnesium and neutral pH conditions induces a pmrAB-dependent, phoP-independent PMB resistance. By contrast, exposure to limiting magnesium triggers a pmrB-, phoP- and pmrD-dependent PMB resistance. The iron-induced PMB resistance is independent of phoP and pmrD under limiting magnesium conditions while the bile-salt-induced PMB resistance is independent of pmrD only under non-PhoP-inducing conditions. GFP-pmrD transcriptional reporter studies reveal that the limiting magnesium enhances pmrD expression, which is repressed upon additional exposure to either BSM or iron. Our results also show that exposure to mild acid enhances PMB resistance in a pmrD-independent manner and GFP reporter results confirm minimal expression of pmrD at this pH regardless of the magnesium level. This study provides novel insights into how EHEC differentially employs PmrAB, PhoPQ and PmrD to monitor and respond to bile salts, iron, acidic pH and magnesium typically encountered within the gastrointestinal tract in order to modulate its survival against cationic antimicrobial peptides.
Accuracy of deep learning based computed tomography diagnostic system of COVID-19: a consecutive sampling external validation cohort study
Authors: Ikenoue Tatsuyoshi , Kataoka Yuki , Matsuoka Yoshinori , Matsumoto Junichi , Kumasawa Junji , Tochitatni Kentaro , Funakoshi Hiraku , Hosoda Tomohiro , Kugimiya Aiko , Shirano Michinori , Hamabe Fumiko , Iwata Sachiyo , Fukuma Shingo ,   Japan COVID-19 AI team
Published: November 2020

Objectives

Ali-M3, an artificial intelligence, analyses chest computed tomography (CT) and detects the likelihood of coronavirus disease (COVID-19) in the range of 0 to 1. It demonstrates excellent performance for the detection of COVID-19 patients with a sensitivity and specificity of 98.5 and 99.2%, respectively. However, Ali-M3 has not been externally validated. Our purpose is to evaluate the external validity of Ali-M3 using Japanese sequential sampling data.

Methods

In this retrospective cohort study, COVID-19 infection probabilities were calculated using Ali-M3 in 617 symptomatic patients who underwent reverse transcription-polymerase chain reaction (RT-PCR) tests and chest CT for COVID-19 diagnosis at 11 Japanese tertiary care facilities, between January 1 and April 15, 2020.

Results

Of 617 patients, 289 patients (46.8%) were RT-PCR-positive. The area under the curve (AUC) of Ali-M3 for predicting a COVID-19 diagnosis was 0.797 (95% confidence intervals [CI]: 0.762-0.833) and goodness-of-fit was P = 0.156. With a cut-off of probability of COVID-19 by Ali-M3 diagnosis set at 0.5, the sensitivity and specificity were 80.6% and 68.3%, respectively, while a cut-off of 0.2 yielded a sensitivity and specificity of 89.2% and 43.2%, respectively. Among 223 patients who required oxygen support, the AUC was 0.825 and sensitivity at a cut-off of 0.5 and 0.2 were 88.7% and 97.9%, respectively. Although the sensitivity was lower when the days from symptom onset were few, sensitivity increased for both cut-off values after 5 days.

Conclusions

Ali-M3 was evaluated by external validation and shown to be useful to exclude a diagnosis of COVID-19.

Key Points

The area under the curve (AUC) of Ali-M3, which is an AI system for diagnosis of COVID-19 based on chest CT images, was 0.797 and goodness-of-fit was P = 0.156.

With a cut-off of probability of COVID-19 by Ali-M3 diagnosis set at 0.5, the sensitivity and specificity were 80.6% and 68.3%, respectively, while a cut-off of 0.2 yielded 89.2% and 43.2%.

Although low sensitivity was observed in less number of days from symptoms onset, after 5 days high increasing sensitivity was observed. In patients requiring oxygen support, the AUC was higher that is 0.825.
The role of blame-related action tendencies in the vulnerability to major depressive disorder
Authors: Duan Suqian , Lawrence Andrew , Valmaggia Lucia , Moll Jorge , Zahn Roland
Published: November 2020

Background

Persisting self-blaming emotional biases were previously associated with vulnerability to major depressive disorder (MDD). More specifically self-contempt/disgust biases distinguished remitted MDD, compared with never-depressed control participants. The contribution of action tendencies to MDD vulnerability and their relationship with blame-related emotions to prepare for subsequent behaviour is elusive. Here, we investigated whether maladaptive action tendencies such as “creating a distance from oneself” and “hiding” are associated with MDD vulnerability, as well as with self-disgust/contempt and shame respectively.

Methods

76 participants with medication-free remitted MDD and 44 healthy control (HC) participants without a personal or family history of MDD completed the value-related moral sentiment task, which measured their blame-related emotions during hypothetical social interactions and a novel task to assess their blame-related action tendencies.

Results

As predicted, the MDD group exhibited a higher proneness to feeling like hiding and creating a distance from themselves compared with the HC group. Interestingly, apologising for one’s wrongdoing, was associated with all self-blaming emotions including shame, guilt, self-contempt/disgust and self-indignation, but was more common in HC. In contrast, apologising and perceiving to be in control of one’s friend’s wrongdoings were more common in MDD. Although shame was indeed associated with hiding, this was also true of guilt. Self-disgust/contempt was associated with attacking rather than creating a distance from oneself.

Conclusions

MDD vulnerability was associated with specific maladaptive action tendencies which were not clearly predicted by the type of emotion, thus unveiling novel cognitive markers and neurocognitive treatment targets.

General Scientific summary

This study confirmed the hypothesis that specific maladaptive action tendencies related to self-blame, such as feeling like hiding and feeling like creating a distance from oneself, were distinctive of people with major depressive disorder, even on remission of symptoms. These action tendencies were not clearly predicted by the type of emotion experienced, showing the importance of assessing them directly. This calls for novel psychological and neurocognitive treatments specifically aiming at maladaptive action tendencies which have so far not been directly addressed in standard assessments and treatments.
The burden of Progressive Fibrotic Interstitial lung disease across the UK
Authors: Simpson Thomas , Barratt Shaney L , Beirne Paul , Chaudhuri Nazia , Crawshaw Anjali , Crowley Louise E , Fletcher Sophie , Gibbons Michael A , Hallchurch Philippa , Horgan Laura , Jakaityte Ieva , Lewis Thomas , McLellan Tom , Miller Ryan , Stanel Stefan , Thillai Muhunthan , Thompson Fiona , Wu Zhe , Molyneaux Philip L , West Alex G
Published: November 2020

While Idiopathic pulmonary fibrosis (IPF) remains the exemplar progressive fibrotic lung disease, there remains a cohort of non-IPF fibrotic lung diseases (fILD) which adopt a similar clinical behaviour to IPF despite therap. This phenotypically related group of conditions, where progression of disease is similar to that seen in IPF, have recently been described as Progressive Fibrotic Interstitial Lung diseases (PF-ILD). Previous estimates suggest that between 18 to 40% of all fILD will develop progressive disease, however, the exact burden remains unknown. This retrospective, observational study therefore aimed to estimate the incidence of PF-ILD across England.

All new referrals seen across nine UK centres for their first outpatient clinic appointment between 1st August 2017 and 31st January 2018 were assessed against the diagnostic criteria for PF-ILD laid out in the INBUILD trial. A total of 1749 patients with fILD were assessed. In this cohort of patients at risk of developing PF-ILD the INBUILD criteria were met in 14.5% (253/1749) of all new non-IPF fILD referrals. The average time from referral to specialist centre to diagnosis of progressive phenotype was 311 days. Of the progression events the majority were driven by a measured drop in FVC, with more than half of patients experiencing a drop of 10%. Almost one quarter of patients (24.1%) were diagnosed with progressive disease on the basis of radiological and symptomatic progression alone without a spirometric deterioration.

This study represents a fair and balanced approach to assessing the incidence of objectively measurable and treatable PF-ILDs in the UK. A rate of 14.5% of new referrals with non-IPF ILD is less than that reported in previous studies however our methodology is likely to give a more accurate result than estimates based on extrapolation from general disease statistics, from physician-reported estimates prone to significant biases, or insurance claim processes also substantially prone to bias. This information has implication for workforce planning and the funding of anti-fibrotic therapy in the UK and beyond.
Involvement of Gut Microbiota in the Development of Psoriasis Vulgaris
Authors: Sun Chaonan , Chen Ling , Yang Huan , Sun Hongjiang , Xie Zhen , Zhao Bei , Jiang Xuemei , Qin Bi , Shen Zhu
Published: November 2020

Background

Psoriasis is a common chronic recurrent dermatitis. Accumulating observations show gut microbiota dysbiosis in psoriasis.

Objectives

We intend to further investigate the relationship between intestinal microbiota and psoriasis development.

Methods

We first performed an epidemiological investigation on differences of gastrointestinal discomfort symptoms between psoriatic patients and general population. Then variation of gut microbiota in psoriatic patients (un)treated with Acitretin was analyzed by 16S rRNA sequencing. We last compared recovery status and vital cytokines of mouse psoriasiform models, which were transplanted with fecal microbiota from psoriatic patients or healthy controls.

Results

(1) 85.53% of psoriatic patients versus 58.08% of healthy controls presented with at least one gastrointestinal symptom. The prevalence of investigated symptoms (e.g. abdominal distension, constipation) were significantly higher in patients, compared with controls (p<0.05). Increased fart and constipation were significantly correlated with psoriasis (p<0.05, respectively). (2) The abundance of Ruminococcaceae family, Coprococcus_1 genus and Blautia genus were significantly decreased with psoriasis improvement, which had been demonstrated significantly increased in psoriasis. (3) Mice receiving psoriatic microflora transplantation showed significantly delayed recovery of psoriasiform dermatitis and less reduction of IL-17A, than those receiving healthy microflora or blank control (p<0.05 and p<0.01, respectively).

Conclusions

Multiple evidences we provided here demonstrate the involvement of gut microbiota in psoriasis development. The strategy based on gut microbiota is expected to be a promising supplementary for long-term management of psoriasis.
Making prognostic algorithms useful in shared decision-making: Patients and clinicians’ requirements for the Predict:Breast Cancer interface
Authors: Farmer G.D. , Pearson G.M. , Skylark W.J. , Freeman A.L.J. , Spiegelhalter D.J.
Published: November 2020

Objectives

To develop a new interface for the widely used prognostic breast cancer tool: PREDICT. To facilitate shared decision-making around post-surgery breast cancer treatments. To derive insights into communicating the outputs of prognostic models to patients and their clinicians.

Method

We applied user-centred design principles in developing a new interface for PREDICT. The research involved online surveys, focus groups, meetings, and usability testing with patients, clinicians and the public.

Results

The new interface has been launched and delivers around 30,000 sessions per month. We identified several principles that are useful when communicating the output of prognostic models, including multiple presentation formats, and contextualising statistics. A programme of future work based on patient and clinician feedback has been developed, including the provision of quantitative data on the adverse effects of adjuvant breast cancer treatments.

Conclusions

For prognostic algorithms to fulfil their potential to assist with shared decision-making they need carefully designed interfaces. User-centred design puts patients and clinicians needs at the forefront, allowing them to derive the maximum benefit from prognostic models.
Socioeconomic determinants of mobility responses during the first wave of COVID-19 in Italy: from provinces to neighbourhoods
Authors: Gauvin Laetitia , Bajardi Paolo , Pepe Emanuele , Lake Brennan , Privitera Filippo , Tizzoni Michele
Published: November 2020

As the second wave of SARS-CoV-2 infections is surging across Europe, it is crucial to identify the drivers of mobility responses to mitigation efforts during different restriction regimes, for planning interventions that are both economically and socially sustainable while effective in controlling the outbreak. Here, using anonymous and privacy enhanced cell phone data from Italy, we investigate the determinants of spatial variations of reductions in mobility and co-location in response to the adoption and the lift of restrictions, considering both provinces and city neighbourhoods. In large urban areas, our analysis uncovers the desertification of historic city centers, which persisted after the end of the lockdown. At the province level, the local structure of the labour market mainly explained the variations in mobility responses, together with other demographic factors, such as population’s age and sex composition. In the future, targeted interventions should take into account how the ability to comply with restrictions varies across geographic areas and socio-demographic groups.
Characteristic of IgA and IgG antibody response to SARS-CoV-2 infection in an Italian referral Covid-19 Hospital
Authors: Annamaria Carnicelli , Barbara Fiori , Rosalba Ricci , Alfonso Piano , Nicola Bonadia , Eleonora Taddei , Massimo Fantoni , Rita Murri , Antonella Cingolani , Christian Barillaro , Lucio Cutuli Salvatore , Debora Marchesini , Davide Antonio Della Polla , Evelina Forte , Mariella Fuorlo , Luca Di Maurizio , Paola Amorini , Francesco Franceschi , Maurizio Sanguinetti
Published: November 2020

Introduction

Antibody response play a fundamental role in the natural history of infectious disease. A better understanding of the immune response in patients with SARS-CoV-2 infection could be important for identifying patients at greater risk of developing a more severe form of disease and with a worse prognosis.

Methods

We performed a cross-sectional analysis to determine the presence and the levels of both anti-SARS-CoV-2 IgG and IgA in a cohort of hospitalized patients with confirmed infection at different times in the natural history of the disease. Patients enrolled when admitted at the emergency department were prospectively followed up during hospital stay.

Results

Overall, 131 patients were considered with a total of 237 samples processed. Cross-sectional analysis showed that seroconversion for IgA seems to occur between days 5 and 15 while IgG response seems to occur slightly later, peaking at day 20 after symptoms onset. Both IgA and IgG were maintained beyond two months. Severe patients showed a higher IgA response compared with mild patients when analyzing optical density (8.3 versus 5.6, p < 0.001). Prospective analysis conducted on 55 patients confirmed that IgA appear slightly earlier than IgG. After stratifying for the severity of disease, both the IgA and IgG response was more vigorous in severe cases. Moreover, while IgG tended to stabilize, there was a relevant decline after the first month of IgA levels in mild cases.

Conclusion

IgA and IgG antibody response is closely related although seroconversion for IgA occurs earlier. Both IgA and IgG are maintained beyond two months. Severe patients showed a more vigorous IgA and IgG response. IgA levels seem to decline after one month since the onset of symptoms in mild cases.
5-Alpha-Reductase Inhibitors Reduce Remission Time of COVID-19: Results From a Randomized Double Blind Placebo Controlled Interventional Trial in 130 SARS-CoV-2 Positive Men
Authors: Cadegiani Flávio Adsuara , McCoy John , Wambier Carlos Gustavo , Goren Andy
Published: November 2020

Background

SARS-CoV-2 entry into type II pneumocytes is depended on the TMPRSS2 proteolytic enzyme. The only known promoter of TMPRSS2 in humans is an androgen response element. As such, androgen sensitivity may be a risk factor for COVID-19. Previously, we have reported a retrospective cohort analysis demonstrating the protective effect of 5-alpha-reductase inhibitors (5ARis) in COVID-19. Men using 5ARis were less likely to be admitted to the ICU than men not taking 5ARis. Additionally, men using 5ARis had drastically reduced frequency of symptoms compared to men not using 5ARis in an outpatient setting. Here we aim to determine if 5ARis will be a beneficial treatment if given after SARS-CoV-2 infection.

Methods

A double-blinded, randomized, prospective, investigational study of dutasteride for the treatment of COVID-19 (NCT04446429). Subjects confirmed positive for SARS-CoV-2 were treated in an outpatient setting. Endpoints for the study were remission times for a predetermined set of symptoms: fever or feeling feverish, cough, shortness of breath, sore throat, body pain or muscle pain/ache, fatigue, headache, nasal congestion, nasal discharge (runny nose), nausea or vomiting, diarrhea, loss of appetite, and loss of taste or smell (Ageusia or Anosmia).

Results

A total of 130 SARS-CoV-2 positive men were included in the study, 64 subjects in the dutasteride arm and 66 subjects in the placebo-controlled group. The differences in the average remission times for fatigue and anosmia or ageusia was statistically different between the groups (5.8 versus 10.1 days for fatigue and 7.3 versus 13.4 days for anosmia or ageusia, in dutasteride and placebo groups, respectively), however, the total remission time was significantly reduced for the men given dutasteride; 9.0 days versus 15.6 days in the placebo group (p < 0.001). Excluding loss of taste and smell the average total remission time was 7.3 days in the dutasteride group versus 11.7 in the placebo arm (p < 0.001).

Conclusion

The total remission time for men using 5ARis was significantly reduced compared to men not taking 5ARis.
RT-LAMP assay for ultra-sensitive detection of SARS-CoV-2 in saliva and VTM clinical samples
Authors: Ganguli A. , Mostafa A. , Berger J. , Stewart de Ramirez S. A. , Baltaji A. , Roth K. , Aamir M. , Aedma S. , Mady M. , Mahajan P. , Sathe S. , Johnson M. , White K. , Kumar J. , Valera E. , Bashir R.
Published: November 2020

The COVID-19 pandemic has underscored the shortcomings in the deployment of state-of-the-art diagnostic platforms. Although several PCR-based techniques have been rapidly developed to meet the growing testing needs, such techniques often need samples collected through a swab, the use of RNA extraction kits, and expensive thermocyclers in order to successfully perform the test. Isothermal amplification-based approaches have also been recently demonstrated for rapid SARS-CoV-2 detection by minimizing sample preparation while also reducing the instrumentation and reaction complexity. There are limited reports of saliva as the sample source and some of these indicate inferior sensitivity when comparing RT-LAMP with PCR-based techniques. In this paper, we demonstrate an improved sensitivity assay to test saliva using a 2-step RT-LAMP assay, where a short 10-minute RT step is performed with only B3 and BIP primers before the final reaction. We show that while the 1-step RT-LAMP demonstrate satisfactory results, the optimized 2-step approach allows for single molecule sensitivity per reaction and performs significantly better than the 1-step RT-LAMP and conventional 2-step RT-LAMP approaches with all primers included in the RT Step. Importantly, we demonstrate RNA extraction-free RT-LAMP based assays for detection of SARS-CoV-2 from VTM and saliva clinical samples.