bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring Peer Support as a Strategy to Reduce Self-Stigma for Marginalised Children of Parents with Mental Illness (COPMI)
Authors: Parkinson Adele , Keddell Emily , Walker Peter
Published: October 2020

Many children of parents with mental illness (COPMI) experience stigma, resulting in detrimental effects and the need for support. Peer support programmes are widespread interventions, commonly providing relational, psychological and educational support. Some evidence suggests that these programmes result in positive changes to COPMI experiences of self, peers and their families. This article adds to the evidence base, presenting findings from a primarily qualitative, mixed-methods programme evaluation of a COPMI service in Aotearoa/New Zealand. Formative evaluation data were gathered from a COPMI service which supports families adversely affected by chronic and severe parental mental illness, via interviews (N = 10) and four age-differentiated focus groups (N = 24) of child/youth service-users aged eight to eighteen years, and mixed-method surveys of adult service-users (N = 32). This article reports data from child/youth service-users who participated. Findings indicate that many participants experienced stigma outside the service, and self-stigma was reduced for many due to supportive peer relationships formed during service delivery. Further understanding of the relationship between peer support and self-stigma in these programmes is needed, and how positive changes to self-perceptions might translate to other spheres. The application of socio-ecological resilience theory to findings implies that COPMI service delivery should address differential needs in relation to marginalisation and promote sustained peer relationships for those who are marginalised.
Dopamine D2R is Required for Hippocampal-dependent Memory and Plasticity at the CA3-CA1 Synapse
Authors: Espadas Isabel , Ortiz Oscar , García-Sanz Patricia , Sanz-Magro Adrián , Alberquilla Samuel , Solis Oscar , Delgado-García José María , Gruart Agnès , Moratalla Rosario
Published: October 2020

Dopamine receptors play an important role in motivational, emotional, and motor responses. In addition, growing evidence suggests a key role of hippocampal dopamine receptors in learning and memory. It is well known that associative learning and synaptic plasticity of CA3-CA1 requires the dopamine D1 receptor (D1R). However, the specific role of the dopamine D2 receptor (D2R) on memory-related neuroplasticity processes is still undefined. Here, by using two models of D2R loss, D2R knockout mice (Drd2−/−) and mice with intrahippocampal injections of Drd2-small interfering RNA (Drd2-siRNA), we aimed to investigate how D2R is involved in learning and memory as well as in long-term potentiation of the hippocampus. Our studies revealed that the genetic inactivation of D2R impaired the spatial memory, associative learning, and the classical conditioning of eyelid responses. Similarly, deletion of D2R reduced the activity-dependent synaptic plasticity in the hippocampal CA1-CA3 synapse. Our results demonstrate the first direct evidence that D2R is essential in behaving mice for trace eye blink conditioning and associated changes in hippocampal synaptic strength. Taken together, these results indicate a key role of D2R in regulating hippocampal plasticity changes and, in consequence, acquisition and consolidation of spatial and associative forms of memory.
Clinical benefits of a swallowing intervention for esophageal cancer patients after esophagectomy
Authors: Takatsu Jun , Higaki Eiji , Hosoi Takahiro , Yoshida Masahiro , Yamamoto Masahiko , Abe Tetsuya , Shimizu Yasuhiro
Published: October 2020

Dysphagia after esophagectomy is the main cause of a prolonged postoperative stay. The present study investigated the effects of a swallowing intervention led by a speech–language–hearing therapist (SLHT) on postoperative dysphagia. We enrolled 276 consecutive esophageal cancer patients who underwent esophagectomy and cervical esophagogastric anastomosis between July 2015 and December 2018; 109 received standard care (control group) and 167 were treated by a swallowing intervention (intervention group). In the intervention group, swallowing function screening and rehabilitation based on each patient’s dysfunction were led by SLHT. The start of oral intake, length of oral intake rehabilitation, and length of the postoperative stay were compared in the two groups. The patient’s subgroups in the 276 patients were examined to clarify the more effectiveness of the intervention. The start of oral intake was significantly earlier in the intervention group (POD: 11 vs. 8 days; P = 0.009). In the subgroup analysis, the length of the postoperative stay was also significantly shortened by the swallowing intervention in patients without complications (POD: 18 vs. 14 days; P = 0.001) and with recurrent laryngeal nerve paralysis (RLNP) (POD: 30 vs. 21.5 days; P = 0.003). A multivariate regression analysis identified the swallowing intervention as a significant independent factor for the earlier start of oral intake and a shorter postoperative stay in patients without complications and with RLNP. Our proposed swallowing intervention is beneficial for the earlier start of oral intake and discharge after esophagectomy, particularly in patients without complications and with RLNP. This program may contribute to enhanced recovery after surgery.
Marked Absences: Locating Gender and Race in International Legal History
Authors: Nijman Janne E
Published: October 2020

This article was sparked by a critical reading of Henri de Waele’s article ‘A New League of Extraordinary Gentlemen? The Professionalization of International Law Scholarship in the Netherlands, 1919–1940’, and aims to offer an alternative perspective on this period in the history of Dutch international legal scholarship. While it appreciates the author’s examination of Dutch international law scholarship during the interwar period and concurs with the idea that this scholarship needs to be examined more closely, it argues that doing history today requires us first to raise ‘the woman question’, especially in the context of the so-called ‘professionalization’ of international law in the 1920s and 1930s, and second to include Dutch colonialism as an important backdrop to the work of the interwar international law scholars. I will give some pointers and illustrations to support this argument. The specific Dutch material brought to bear aims to show more generally the importance of questioning rather than reproducing traditional historiography, within which ‘the woman question’ and ‘the colonial question’ were left unmentioned. As such this article also deals with the issue of expanding and remaking international legal history as an issue of present and future purport.
Accuracy of an automated method of 3D soft tissue landmark detection
Authors: Baksi Sanjana , Freezer Simon , Matsumoto Takeshi , Dreyer Craig
Published: October 2020

Introduction

Due to technological advances, the quantification of facial form can now be done via three-dimensional (3D) photographic systems such as stereophotogrammetry. To enable comparison with traditional cephalometry, soft-tissue anatomical landmark definitions have been modified to incorporate the third dimension. Annotating these landmarks manually, however, is still a time-consuming and arduous process.

Objective

To develop an automated algorithm to accurately identify anatomical landmarks on three-dimensional soft tissue images.

Methods

Thirty 3dMD images were selected from a private orthodontic practice consisting of 15 males and 15 females between 9 and 17 years of age. The soft-tissue 3D images were aligned along a reference plane to setup a Cartesian coordinate system. Screened by 2 observers, 21 landmarks were manually annotated and their coordinates defined. An automated landmark identification algorithm, based on their anatomical definitions, was developed to compare the landmark validity against the manually identified counterpart.

Results

Twenty-one landmarks were analysed in detail. Inter-observer and intra-observer reliability using ICC was >0.9. The average difference and standard deviation between manual and automated methods for all landmarks was 3.2 and 1.64 mm, respectively. Sixteen out of twenty-one landmarks had a mean difference less than 4 mm. The landmarks of greatest agreement (≤2 mm) were mainly in the midline: pronasale, subnasale, subspinale, labiale superius, stomion, with the exception of chelion right. Five linear facial measurements were found to have moderate to good agreement between the manual and automated identification methods.

Conclusions

The developed algorithm was determined to be clinically relevant in the detection of midsagittal landmarks and associated measurements within the studied sample of adolescent Caucasian subjects.
Attitudes of medical students to general practice: a multinational cross-sectional survey
Authors: Avian Alexander , Poggenburg Stephanie , Schaffler-Schaden Dagmar , Hoffmann Kathryn , Sanftenberg Linda , Loukanova Svetla , Bachler Herbert , Gehrke-Beck Sabine , Petek Ster Marija , Becker Annette , Herrmann Markus , Frese Thomas , Gerlach Ferdinand , Zelko Erika , Flamm Maria , Roos Marco , Freitag Michael , Schirgi Julia , Rieder Anita , Siebenhofer Andrea
Published: October 2020

Background

A shortage of general practitioners (GPs) is common to many European countries. To counteract this, it is essential to understand the factors that encourage or discourage medical students from choosing to become a GP

Objective

To evaluate medical students’ attitudes towards general practice and to identify factors that discourage them from considering a career as a GP.

Methods

In this multinational cross-sectional online survey, 29 284 students from nine German, four Austrian and two Slovenian universities were invited to answer a questionnaire consisting of 146 closed and 13 open-ended items.

Results

Of the 4486 students that responded (response rate: 15.3%), 3.6% wanted to become a GP, 48.1% were undecided and 34.6% did not want to be a GP. Significant predictors for interest in becoming a GP were higher age [odds ratio (OR) = 1.06; 95% confidence interval (CI) = 1.02–1.10], positive evaluation of the content of a GP’s work (OR = 4.44; 95% CI = 3.26–6.06), organizational aspects (OR = 1.42; 95% CI = 1.13–1.78), practical experience of general practice (OR = 1.66; 95% CI = 1.08–2.56) and the country of the survey [Slovenian versus German students (Reference): OR = 2.19; 95% CI = 1.10–4.38; Austrian versus German students (Reference): OR = 0.50; 95% CI = 0.32–0.79].

Conclusion

Strategies to convince undecided students to opt for a career as a GP should include a positive representation of a GP’s work and early and repeated experience of working in a general practice during medical school.
“A Toxic Trend?”: Generational Conflict and Connectivity in Twitter Discourse Under the #BoomerRemover Hashtag
Authors: Sipocz Daniel , Freeman Jessica D , Elton Jessica
Published: October 2020

Background and Objectives

This study examines the #BoomerRemover hashtag on Twitter to understand discourses of intergenerational conflict and unity that emerged during the novel coronavirus disease 2019 global pandemic. The research highlights conflict and connection surrounding generational cohorts via social media, particularly in a time of crisis.

Research Design and Methods

The study used an inductive-dominant qualitative content analysis to examine 536 tweets collected between March 9 and April 9, 2020 under #BoomerRemover.

Results

Data analysis revealed five forms of conflictive generational discourse: derogatory endorsement of the #BoomerRemover moniker, conflict regarding the nature and origins of the moniker, conflict surrounding the virus, political conflict, and generational jabs. Two forms of intergenerationally unifying discourse were identified: implicit and explicit pleas for connectivity.

Discussion and Implications

The analysis of discourse under #BoomerRemover revealed more nuanced expressions surrounding generational cohorts than widely reported in media outlets. Some users tweeted the hashtag in ways that reflected conflict, with #BoomerRemover acting as a vector through which stereotypes were perpetuated and magnified. However, a number of users tweeted the hashtag to call for intergenerational connectivity, highlighting the complexity of online discourse. These results yield implications for the study of online generational discourse, particularly in light of the unique circumstances surrounding the pandemic.
Immune profiling after minimally invasive lobectomy
Authors: Erus Suat , Öztürk Ayşe Bilge , Albayrak Özgür , İncir Said , Kapdağlı Murat Hüseyin , Cesur Ekin Ezgi , Yavuz Ömer , Tanju Serhan , Dilege Şükrü
Published: October 2020

OBJECTIVES

Whether acute phase and immune responses are minimally affected following minimally invasive lung surgery needs further investigation. We performed a pilot study to evaluate the immune profile of patients who underwent video-assisted thoracoscopic surgery or robot-assisted thoracic surgery lobectomies for the treatment of suspicious or known stage I non-small-cell lung cancer.

METHODS

Blood samples were taken preoperatively and 3 and 24 h postoperatively were analysed for C-reactive protein, glucose, cortisol, tumour necrosis factor alpha (TNF-α), interleukin 8 (IL-8) and interleukin 10 (IL-10) levels. TNF-α, IL-8 and IL-10 were also measured in lung tissues. T (CD4, CD8), B (CD19) and natural killer (CD56, CD16) cell counts and natural killer cell functions were analysed using a flow cytometry-based assay before and after surgery.

RESULTS

Minimally invasive surgery (robot-assisted thoracic surgery + video-assisted thoracoscopic surgery) significantly decreased IL-10 (P = 0.016) levels after surgery. No significant differences were detected in TNF-α (P = 0.48) and IL-8 (P = 0.15) levels before and after surgery. C-reactive protein (P < 0.001), cortisol (P < 0.001) and glucose levels (P < 0.001) increased significantly after surgery. Lymphocyte, total T cell, CD3+CD4+ and CD3+CD8+ CD16+CD56+ cell counts were significantly lower on postoperative day 1.

CONCLUSION

There seems to be a dynamic balance between pro- and anti-inflammatory cytokines and immune cells following minimally invasive lobectomy.
Solomon-Tukachinsky’s Versus Welschinger’s Open Gromov-Witten Invariants of Symplectic Six-Folds
Authors: Chen Xujia
Published: October 2020

Our previous paper describes a geometric translation of the construction of open Gromov–Witten invariants by Solomon and Tukachinsky from a perspective of $A_{\infty }$-algebras of differential forms. We now use this geometric perspective to show that these invariants reduce to Welschinger’s open Gromov–Witten invariants in dimension 6, inline with their and Tian’s expectations. As an immediate corollary, we obtain a translation of Solomon–Tukachinsky’s open WDVV equations into relations for Welschinger’s invariants.
A Critical Role for STING Signaling in Limiting Pathogenesis of Chikungunya Virus
Authors: Geng Tingting , Lin Tao , Yang Duomeng , Harrison Andrew G , Vella Anthony T , Fikrig Erol , Wang Penghua
Published: October 2020

The stimulator of interferon gene (STING) pathway controls both DNA and RNA virus infection. STING is essential for induction of innate immune responses during DNA virus infection, while its mechanism against RNA virus remains largely elusive. We show that STING signaling is crucial for restricting chikungunya virus infection and arthritis pathogenesis. Sting-deficient mice (Stinggt/gt) had elevated viremia throughout the viremic stage and viral burden in feet transiently, with a normal type I IFN response. Stinggt/gt mice presented much greater foot swelling, joint damage, and immune cell infiltration than wild-type mice. Intriguingly, expression of interferon-γ and Cxcl10 was continuously upregulated by approximately 7 to 10-fold and further elevated in Stinggt/gt mice synchronously with arthritis progression. However, expression of chemoattractants for and activators of neutrophils, Cxcl5, Cxcl7, and Cxcr2 was suppressed in Stinggt/gt joints. These results demonstrate that STING deficiency leads to an aberrant chemokine response that promotes pathogenesis of CHIKV arthritis.
Effects of dietary soluble or insoluble fiber intake in late gestation on litter performance, milk composition, immune function, and redox status of sows around parturition
Authors: Liu Yang , Chen Nan , Li Dan , Li Hua , Fang Zhengfeng , Lin Yan , Xu Shengyu , Feng Bin , Zhuo Yong , Wu De , Theil Peter Kappel , Che Lianqiang
Published: October 2020

The objective of this study was to investigate the effects of dietary soluble fiber (SF) or insoluble fiber (ISF) intake in late gestation on litter performance, milk composition, immune function, and redox status of sows around parturition. A total of 60 Yorkshire sows were randomly assigned into three dietary treatments: normal level of dietary fiber (CON, 16.16% dietary fiber with 1.78% soluble fiber and 14.38% insoluble fiber), high insoluble fiber (ISF, 30.12% dietary fiber with 2.97% soluble fiber and 27.15% insoluble fiber), and high soluble fiber (SF, 30.15% dietary fiber with 4.57% soluble fiber and 25.58% insoluble fiber). Digestible energy and crude protein intake were comparable among treatments via adjusting feed intake from day 90 of gestation to parturition. After parturition, all sows were fed the same lactation diet. Results showed that litter performance of sows was not markedly affected by maternal fiber intake. However, sows fed ISF or SF diet had increased concentration of plasma mmunoglobulin G at day 107 (P < 0.05) and parturition (P < 0.01), and the SF diet had a tendency to increase fat content in both colostrum and milk relative to the CON diet. Furthermore, sows fed ISF diet had increased glutathione peroxidase activity (P < 0.05) at day 107, but decreased the plasma level of malondialdehyde at parturition (P < 0.05). High maternal SF intake tended to decrease the number of weaned piglets due to the increased preweaning mortality, as compared with sows fed the ISF diet. In conclusion, high fiber intake in late gestation may improve immune function and redox status, but differentially influenced the milk composition and preweaning mortality.
No Justice Without Peace, But What Peace Is on Offer?
Authors: Kersten Mark
Published: October 2020

Does the potential investigation into Palestine by the International Criminal Court (ICC) threaten the chances of a lasting ‘peace’ between Israel and Palestine? This article endeavours to answer that question and critically assesses claims that the Court could undermine peace in the Middle East. I first examine the key claims made in the so-called ‘peace versus justice’ debate. I then outline some of the specific arguments made in the context of a possible ICC investigation in Palestine that touch upon concerns over the Court’s impacts on peace processes and negotiations. Following this, I try to assess critically the validity of these claims, arguing that while it would be wrong to conclude that the ICC will invariably have positive impacts on efforts to establish peace, there is no evidence that the Court will undermine whatever ‘peace’ is currently on offer for Palestinians and Israelis. On the contrary, this ‘peace’ may itself be a threat to resolving the conflict peaceably and to long-term stability in the region. Finally, I conclude the article with some reflections on the peace-justice debate and its applicability to the Israel–Palestine situation.
Impact of the COVID-19 Pandemic on Patient-Reported Outcomes of Breast Cancer Patients and Survivors
Authors: Bargon Claudia A , Batenburg Marilot C T , van Stam Lilianne E , Mink van der Molen Dieuwke R , van Dam Iris E , van der Leij Femke , Baas Inge O , Ernst Miranda F , Maarse Wiesje , Vermulst Nieke , Schoenmaeckers Ernst J P , van Dalen Thijs , Bijlsma Rhodé M , Young-Afat Danny A , Doeksen Annemiek , Verkooijen Helena M
Published: October 2020

Background

The coronavirus disease 2019 (COVID-19) pandemic (officially declared on the March 11, 2020), and the resulting measures, are impacting daily life and medical management of breast cancer patients and survivors. We evaluated to what extent these changes have affected quality of life, physical, and psychosocial well-being of patients previously or currently being treated for breast cancer.

Methods

This study was conducted within a prospective, multicenter cohort of breast cancer patients and survivors (Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion). Shortly after the implementation of COVID-19 measures, an extra survey was sent to 1595 participants, including the validated European Organization for Research and Treatment of Cancer (EORTC) core (C30) and breast cancer-

specific (BR23) Quality of Life Questionnaire (EORTC QLQ-C30/BR23) and Hospital Anxiety and Depression Scale (HADS) questionnaire. Patient-reported outcomes (PROs) were compared with the most recent PROs collected within UMBRELLA pre–COVID-19. The impact of COVID-19 on PROs was assessed using mixed model analysis, adjusting for potential confounders.

Results

1051 patients and survivors (65.9%) completed the survey; 31.1% (n = 327) reported a higher threshold to contact their general practitioner amid the COVID-19 pandemic. A statistically significant deterioration in emotional functioning was observed (mean = 82.6 [SD = 18.7] to 77.9 [SD = 17.3]; P < .001), and 505 (48.0%, 95% confidence interval [CI] = 45.0% to 51.1%) patients and survivors reported moderate to severe loneliness. Small improvements were observed in quality of life and physical, social, and role functioning. In the subgroup of 51 patients under active treatment, social functioning strongly deteriorated (77.3 [95% CI = 69.4 to 85.2] to 61.3 [95% CI = 52.6 to 70.1]; P = .002).

Conclusion

During the COVID-19 pandemic, breast cancer patients and survivors were less likely to contact physicians and experienced a deterioration in their emotional functioning. Patients undergoing active treatment reported a substantial drop in social functioning. One in 2 reported loneliness that was moderate or severe. Online interventions supporting mental health and social interaction are needed during times of social distancing and lockdowns.
Arabidopsis ORANGE protein regulates plastid pre-protein import through interacting with Tic proteins
Authors: Yuan Hui , Pawlowski Emily G , Yang Yong , Sun Tianhu , Thannhauser Theodore W , Mazourek Michael , Schnell Danny , Li Li
Published: October 2020

Chloroplast-targeted proteins are actively imported into chloroplasts via the machinery spanning the double-layered membranes of chloroplasts. While the key translocons at the outer (TOC) and inner (TIC) membranes of chloroplasts are defined, proteins that interact with the core components to facilitate pre-protein import are continuously being discovered. A DnaJ-like chaperone ORANGE (OR) protein is known to regulate carotenoid biosynthesis as well as plastid biogenesis and development. In this study, we found that OR physically interacts with several Tic proteins including Tic20, Tic40, and Tic110 in the classic TIC core complex of the chloroplast import machinery. Knocking out or and its homolog or-like greatly affects the import efficiency of some photosynthetic and non-photosynthetic pre-proteins. Consistent with the direct interactions of OR with Tic proteins, the binding efficiency assay revealed that the effect of OR occurs at translocation at the inner envelope membrane (i.e. at the TIC complex). OR is able to reduce the Tic40 protein turnover rate through its chaperone activity. Moreover, OR was found to interfere with the interaction between Tic40 and Tic110, and reduces the binding of pre-proteins to Tic110 in aiding their release for translocation and processing. Our findings suggest that OR plays a new and regulatory role in stabilizing key translocons and in facilitating the late stage of plastid pre-protein translocation to regulate plastid pre-protein import.
Stellar parameter determination from photometry using invertible neural networks
Authors: Ksoll Victor F , Ardizzone Lynton , Klessen Ralf , Koethe Ullrich , Sabbi Elena , Robberto Massimo , Gouliermis Dimitrios , Rother Carsten , Zeidler Peter , Gennaro Mario
Published: October 2020

Photometric surveys with the Hubble Space Telescope (HST) allow us to study stellar populations with high-resolution and deep coverage, with estimates of the physical parameters of the constituent stars being typically obtained by comparing the survey data with adequate stellar evolutionary models. This is a highly non-trivial task due to effects such as differential extinction, photometric errors, low filter coverage, or uncertainties in the stellar evolution calculations. These introduce degeneracies that are difficult to detect and break. To improve this situation, we introduce a novel deep learning approach, called conditional invertible neural network (cINN), to solve the inverse problem of predicting physical parameters from photometry on an individual star basis and to obtain the full posterior distributions. We build a carefully curated synthetic training data set derived from the PARSEC stellar evolution models to predict stellar age, initial/current mass, luminosity, effective temperature, and surface gravity. We perform tests on synthetic data from the MIST and Dartmouth models, and benchmark our approach on HST data of two well-studied stellar clusters, Westerlund 2 and NGC 6397. For the synthetic data, we find overall excellent performance, and note that age is the most difficult parameter to constrain. For the benchmark clusters, we retrieve reasonable results and confirm previous findings for Westerlund 2 on cluster age ($1.04_{-0.90}^{+8.48}\, \mathrm{Myr}$), mass segregation, and the stellar initial mass function. For NGC 6397, we recover plausible estimates for masses, luminosities, and temperatures, however, discrepancies between stellar evolution models and observations prevent an acceptable recovery of age for old stars.
Source and symptoms of COVID-19 among hospital workers in Milan
Authors: Mandić-Rajčević S , Masci F , Crespi E , Franchetti S , Longo A , Bollina I , Velocci S , Amorosi A , Baldelli R , Boselli L , Negroni L , Zà A , Orfeo N V , Ortisi G , Centanni S , Colosio C
Published: October 2020

Background

Healthcare workers (HCWs) are commonly infected by SARS-CoV-2 and represent one of the most vulnerable groups. Adequate prevention strategies are necessary to guarantee HCWs’ safety, as well as to prevent dissemination of the infection among patients.

Aims

To describe a case series of SARS-CoV-2-positive HCWs in a large public healthcare organization in Milan (Italy) during the most devastating weeks of the epidemic and analyse the sources, symptoms and duration of SARS-CoV-2 infection.

Methods

This study included 172 SARS-CoV-2-positive HCWs who were infected between the 25th of February and the 7th of April 2020. A nasopharyngeal swab (NPS) and RT-PCR were used to indicate.

Results

Initially, the most common sources of infection were other positive HCWs (49%). Medical doctors and nursing assistants were most frequently infected, with infection rates of 53/1000 and 50/1000, respectively. COVID-19 departments were less affected than internal medicine, surgery, intensive care, or emergency room. The most commonly reported symptom was mild cough, while loss of smell (anosmia) and loss of taste (ageusia) were reported as moderate and severe by 30–40% of HCWs. The time necessary for 50% of workers to recover from the infection was 23 days, while it took 41 days for 95% of HCWs to become virus-free.

Conclusions

HCWs are commonly infected due to close contacts with other positive HCWs, and non-COVID departments were most affected. Most HCWs were asymptomatic or subclinical but contact tracing and testing of asymptomatic HCWs help identify and isolate infected workers.
Development and internal validation of a diagnostic prediction model for COVID-19 at time of admission to hospital
Authors: Fink D L , Khan P Y , Goldman N , Cai J , Hone L , Mooney C , El-Shakankery K H , Sismey G , Whitford V , Marks M , Thomas S
Published: October 2020

Background

Early coronavirus disease 2019 (COVID-19) diagnosis prior to laboratory testing results is crucial for infection control in hospitals. Models exist predicting COVID-19 diagnosis, but significant concerns exist regarding methodology and generalizability.

Aim

To generate the first COVID-19 diagnosis risk score for use at the time of hospital admission using the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) checklist.

Design

A multivariable diagnostic prediction model for COVID-19 using the TRIPOD checklist applied to a large single-centre retrospective observational study of patients with suspected COVID-19.

Methods

581 individuals were admitted with suspected COVID-19; the majority had laboratory-confirmed COVID-19 (420/581, 72.2%). Retrospective collection was performed of electronic clinical records and pathology data.

Results

The final multivariable model demonstrated AUC 0.8535 (95% confidence interval 0.8121–0.8950). The final model used six clinical variables that are routinely available in most low and high-resource settings. Using a cut-off of 2, the derived risk score has a sensitivity of 78.1% and specificity of 86.8%. At COVID-19 prevalence of 10% the model has a negative predictive value (NPV) of 96.5%.

Conclusions

Our risk score is intended for diagnosis of COVID-19 in individuals admitted to hospital with suspected COVID-19. The score is the first developed for COVID-19 diagnosis using the TRIPOD checklist. It may be effective as a tool to rule out COVID-19 and function at different pandemic phases of variable COVID-19 prevalence. The simple score could be used by any healthcare worker to support hospital infection control prior to laboratory testing results.
Motivational Ratings
Authors: Hörner Johannes , Lambert Nicolas S
Published: October 2020

Performance evaluation (“rating”) systems not only provide information to users but also motivate the rated worker. This article solves for the optimal (effort-maximizing) rating within the standard career concerns framework. We prove that this rating is a linear function of past observations. The rating, however, is not a Markov process, but rather the sum of two Markov processes. We show how it combines information of different types and vintages. An increase in effort may adversely affect some (but not all) future ratings.
Osteosarcopenia: where osteoporosis and sarcopenia collide
Authors: Clynes Michael A , Gregson Celia L , Bruyère Olivier , Cooper Cyrus , Dennison Elaine M
Published: October 2020

The coexistence of osteoporosis and sarcopenia has been recently considered in some groups as a syndrome termed ‘osteosarcopenia’. Osteoporosis describes low bone mass and deterioration of the micro-architecture of the bone, whereas sarcopenia is the loss of muscle mass, strength and function. With an ageing population the prevalence of both conditions is likely to increase substantially over the coming decades and is associated with significant personal and societal burden. The sequelae for an individual suffering from both conditions together include a greater risk of falls, fractures, institutionalization and mortality. The aetiology of ‘osteosarcopenia’ is multifactorial with several factors linking muscle and bone function, including genetics, age, inflammation and obesity. Several biochemical pathways have been identified that are facilitating the development of several promising therapeutic agents, which target both muscle and bone. In the current review we outline the epidemiology, pathogenesis and clinical consequences of ‘osteosarcopenia’ and explore current and potential future management strategies.
Equilibrium Asset Pricing in Directed Networks*
Authors: Branger Nicole , Konermann Patrick , Meinerding Christoph , Schlag Christian
Published: October 2020

Directed links in cash flow networks affect the cross-section of risk premia through three channels. In a tractable consumption-based equilibrium asset pricing model, we obtain closed-form solutions that disentangle these channels for arbitrary directed networks. First, shocks that can propagate through the economy command a higher market price of risk. Second, shock-receiving assets earn an extra premium since their valuation ratios drop upon shocks in connected assets. Third, a hedge effect pushes risk premia down: when a shock propagates through the economy, an asset that is unconnected becomes relatively more attractive and its valuation ratio increases.
Time to Mycoplasma Pneumoniae RNA Clearance for Wheezy vs. Non-Wheezy Young Children with Community-Acquired Pneumonia
Authors: Chen Jiande , Ji Fengjuan , Yin Yong , Yuan Shuhua
Published: October 2020

Objectives

We sought to investigate the dynamics of Mycoplasma pneumoniae (Mp) RNA in hospitalized young children with community-acquired pneumonia (CAP) and to explore whether Mp RNA clearance differed for wheezy and non-wheezy group after the onset of azithromycin treatment.

Methods

We included hospitalized young children (1–72 months of age) with CAP caused by Mp infection. Mp RNA was detected as soon as the patient was admitted and the dynamics of Mp-RNA were monitored after the beginning of azithromycin treatment on Days 4, 7, 14 and 28.

Results

Among 40 hospitalized young children with Mycoplasma pneumoniae pneumonia (Mpp), 16 had wheezing. Time to first positive Mp-RNA confirmation after symptom onset of Mpp was similar for the wheezy group (median 7 days, interquartile range 7–10.5) and the non-wheezy group (median 7 days, interquartile range 5.8–8.3). The duration of positive Mp-RNA detection after the onset of azithromycin treatment was shorter among the wheezy group than in the non-wheezy group (median 4 vs. 7 days; hazard ratio 2.083; 95% confidence interval: 1.023–4.244).

Conclusions

Mp-RNA clearance was significantly faster among Mpp young children with wheezing than in those without wheezing after the onset of azithromycin treatment.

Lay summary

We sought to investigate the dynamics of Mycoplasma pneumoniae (Mp) RNA in hospitalized young children with community-acquired pneumonia and to explore whether Mp RNA clearance differed for wheezy and non-wheezy group after the onset of azithromycin treatment. Our study suggested that Mp-RNA clearance was significantly faster among Mycoplasma pneumoniae pneumonia young children with wheezing than in those without wheezing after the onset of azithromycin treatment.
Urinary metabolite profiling identifies biomarkers for risk of progression of diabetic nephropathy in 2,670 individuals with type 1 diabetes
Authors: Mutter Stefan , Valo Erkka , Aittomäki Viljami , Nybo Kristian , Raivonen Lassi , Thorn Lena M , Forsblom Carol , Sandholm Niina , Würtz Peter , Groop Per-Henrik
Published: October 2020

Aims

This study examines associations between 51 urinary metabolites and risk of progression of diabetic nephropathy in individuals with type 1 diabetes by employing an automated nuclear magnetic resonance (NMR) metabolomics technique suitable for large-scale urine sample collections.

Methods

For 2,670 individuals with type 1 diabetes from the FinnDiane Study, we collected 24-hour urine samples and measured metabolite concentrations by NMR. Individuals were followed for 9.0 ± 5.0 years until their first sign of progression of diabetic nephropathy, end-stage kidney disease or study end. Cox regression analyses were performed on the entire study population (overall progression), on 1,999 individuals with normoalbuminuria and 347 individuals with macroalbuminuria at baseline.

Results

Seven urinary metabolites were associated with overall progression after adjustment for baseline albuminuria and chronic kidney disease stage (p < 8 × 10-4): Leucine (hazard ratio 1.47, 95% confidence interval [1.30, 1.66] per 1-SD creatinine-scaled metabolite concentration), valine (1.38 [1.22, 1.56]), isoleucine (1.33 [1.18, 1.50]), pseudouridine (1.25 [1.11, 1.42]), threonine (1.27 [1.11, 1.46]) and citrate (0.84 [0.75, 0.93]). 2-hydroxyisobutyrate was associated with overall (1.30 [1.16, 1.45]) and also progression from normoalbuminuria (1.56 [1.25, 1.95]). Six amino acids and pyroglutamate were associated with progression from macroalbuminuria.

Conclusions

Branched-amino acids and other urinary metabolites were associated with the progression of diabetic nephropathy on top of baseline albuminuria and chronic kidney disease. We found differences in associations for overall progression and progression from normo- and macroalbuminuria. These novel biomarker discoveries illustrate the utility of analysing urinary metabolites in entire population cohorts.

Significance Statement

Individuals with type 1 diabetes are vulnerable to diabetic nephropathy and would benefit from earlier detection of disease progression. Urinary metabolites as a direct read-out of kidney function are potential progression markers. However, analytical tools to quantify a broad panel of urinary metabolites at large scale and low cost are lacking. Recent developments in nuclear magnetic resonance address this need. This study in 2,670 individuals with type 1 diabetes identified ten urinary metabolites associated with progression of diabetic nephropathy. Importantly, different albuminuria categories had different urinary profiles: 2-hydroxyisobutyrate was associated with progression from normoalbuminuria and branched-chain amino acids with progression from macroalbuminuria. These results provide new potential biomarkers and highlight the potential of analysing urinary metabolites on a larger scale.
Clinico-laboratory profile, intensive care needs, treatment details, and outcome of Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): A systematic review and Meta-analysis
Authors: Williams Vijai , Dash Nabaneeta , Suthar Renu , Mohandoss Vichithra , Jaiswal Nishant , Kavitha TK , Nallasamy Karthi , Angurana Suresh Kumar
Published: October 2020

Objectives

To synthesize the current data on clinico-laboratory features, intensive care needs, treatment, and outcome of Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C).

Data Sources

Articles published in PubMed, Web of Science, Scopus, Google Scholar, and WHO COVID-19 research database, CDC database, and Cochrane COVID-19 study register between 1stDecember 2019 to 10thJuly 2020.

Study Selection

Observational studies involving patients ≤21 years with PIMS-TS or MIS-C, that reported the clinico-laboratory features, intensive care needs, treatment, and outcome.

Data Extraction

The search identified 422 citations and finally 18 studies with 833 participants were included and pooled estimate was calculated for parameters of interest utilising random effect model.

Data Synthesis

The median age was 9 (8-11) years. Fever, gastrointestinal symptoms, rash, conjunctival injection, and respiratory symptoms were common clinical features. Majority had positive SARS-CoV-2 antibody test and only 1/3rdhad RT-PCR positive. The commonest laboratory abnormalities were elevated CRP, D-dimer, procalcitonin, BNP, fibrinogen, ferritin, troponin, and IL-6; and lymphopenia, hypoalbuminemia, and thrombocytopenia. The cardiovascular complications included shock (65%), myocardial dysfunction (61%), myocarditis (65%), and coronary artery abnormalities (39%). Three-fourth children required admission in PICU for mechanical ventilation (25%) and vasoactive drugs (61%). The common treatment provided was IVIG (82%), steroids (54%), antiplatelet drugs (64%), and anticoagulation (51%). The mortality was low (n=13).

Conclusion

Fever, gastrointestinal and mucocutaneous symptoms, cardiac dysfunction, shock, and hyperinflammation are common manifestations of PIMS-TS or MIS-C. The short-term outcome is good with supportive intensive care and immunomodulatory treatment.
Epidemiological, clinical, and laboratory findings for patients of different age groups with confirmed coronavirus disease 2019 (COVID-19) in a hospital in Saudi Arabia
Authors: Ibrahim Mutasim E. , AL-Aklobi Obaid S. , Abomughaid Mosleh M. , Al-Ghamdi Mushabab A.
Published: October 2020

Background

Although the coronavirus disease 2019 (COVID-19) pandemic continues to rage worldwide, clinical and laboratory studies of this disease have been limited in many countries. We investigated the epidemiologic, clinical, and laboratory findings of COVID-19 infected patients to identify the effective indicators correlated with the disease.

Methods

A retrospective study was conducted at King Abdullah Hospital in Bisha Province, Saudi Arabia, from March 20 to June 30, 2020. Patients of different age groups were confirmed as having COVID-19 infection using a real-time polymerase chain reaction. The demographic, clinical, and laboratory data of the patients were statistically analyzed.

Results

Of the 137 patients, 88 were male and 49 were female, with a mean age of 49.3 years (SD±18.4). The patients were elderly (n=29), adults (n=103), and children (n=5). Of these, 54 (39.4%) had comorbidities, 24% were admitted to the intensive care unit (ICU), and 12 (8.8%) died. On admission, the main clinical manifestations were fever (82.5%), cough (63.5%), shortness of breath (24.8%), chest pain (19.7%), and fatigue (18.2%).

In all patients, increased neutrophils and decreased lymphocytes were observed. Patients’ lactate dehydrogenase (LDH) was elevated. C-reactive protein (CRP) was elevated in 46.7%, D-dimer in 41.6%, and the erythrocyte sedimentation rate (ESR) in 39.4% of patients. The elderly showed higher neutrophil (p=0.003) and lower lymphocyte (p=0.001) counts than adults and children. Glucose, creatine kinase-MB, LDH, bilirubin, D-dimer, and ESR were significantly higher in the elderly than in the adults. The COVID-19 death group had a higher leucocyte count (p = 0.043), and higher urea (p=0.025) and potassium (p=0.026) than the recovered group but had a lower hemoglobin concentration (p=0.018). A significant association was determined between COVID-19 death (χ2(1)=17.751, p<0.001), and the presence of cardiovascular disease (χ2(1)=17.049, p<0.001), hypertension (χ2(1)=7.659, p=0.006), renal failure (χ2(1)=4.172, p<0.04), old age (t(135) = 4.747, p <0.001), and ICU admission (χ2(1) = 17.751 (1), p<0.001).

Conclusions

The common symptoms found in this study could be useful for identifying potential COVID-19 patients. Investigating some of the laboratory and clinical parameters could help assess the disease progression, risk of mortality, and follow up patients who could progress to a fatal condition.
Spatial autocorrelation and the dynamics of the mean center of COVID-19 infections in Lebanon
Authors: El Deeb Omar
Published: October 2020

In this paper we study the spatial spread of the COVID-19 infection in Lebanon. We inspect the spreading of the daily new infections across the 26 administrative districts of the country, and implement Moran’s I statistics in order to analyze the tempo-spatial clustering of the infection in relation to various variables parameterized by adjacency, proximity, population, population density, poverty rate and poverty density, and we find out that except for the poverty rate, the spread of the infection is clustered and associated to those parameters with varying magnitude for the time span between July (geographic adjacency and proximity) or August (population, population density and poverty density) through October. We also determine the temporal dynamics of geographic location of the mean center of new and cumulative infections since late March. The results obtained allow for regionally and locally adjusted health policies and measures that would provide higher levels of public health safety in the country.
In vivoprogressive degeneration of Huntington’s disease patient-derived neurons reveals human-specific pathological phenotypes
Authors: Miguez Andrés , Fernández-García Sara , Monguió-Tortajada Marta , Bombau Georgina , Galofré Mireia , García-Bravo María , Vila Cristina , Sanders Phil , Fernández-Medina Helena , Poquet Blanca , Salado-Manzano Cristina , Roura Santiago , Alberch Jordi , Segovia José Carlos , Allen Nicholas D. , Borràs Francesc E. , Canals Josep M.
Published: October 2020

Research on neurodegenerative disorders has been hampered by the limited access to patients’ brain tissue and the absence of relevant physiological models with human neurons, accounting for the little success of clinical trials. Moreover, post-mortem samples cannot provide a detailed picture of the complex pathological mechanisms taking place throughout the course of the disease. This holds particularly true for Huntington’s disease (HD), an incurable inherited brain disorder marked by a massive striatal degeneration due to abnormal accumulation of misfolded huntingtin protein. To characterize progressive human neurodegenerationin vivo, we transplanted induced pluripotent stem cell-derived human neural progenitor cells (hNPCs) from control (CTR-hNPCs) and HD patients (HD-hNPCs) into the striatum of neonatal wild-type mice. Implanted human cells were examined by immunohistochemistry and electron microscopy, and chimeric mice were subjected to behavioral testing. Most grafted hNPCs differentiated into striatal neurons that sent axonal projections to their natural targets and established synaptic connections within the host basal ganglia circuitry. HD-hNPCs first showed developmental abnormalities characterized by an increased proliferation and accelerated medium spiny neuron (MSN) differentiation, mimicking the initial striatal hypertrophy of child mutant huntingtin (mHTT) carriers. HD human striatal neurons progressively developed mHTT oligomers and aggregates, which primarily targeted mitochondria, endoplasmic reticulum and nuclear membrane to cause structural alterations. Five months after transplantation, selective death of human MSNs and striatal degeneration altered mouse behavior, suggesting disease propagation to non-mutated host cells. Histological analysis and co-culture experiments revealed that HD-hNPCs secreted extracellular vesicles containing soluble mHTT oligomers, which were internalized by mouse striatal neurons triggering cell death. Finally,in vivopharmacological inhibition of the exosomal secretory pathway through sphingosine-1 phosphate receptor functional antagonism, limited the spreading of apoptosis within the host striatum. Our findings cast new light on human neurodegeneration, unveiling cell and non-cell autonomous mechanisms that drive HD progression in patients.