bluuebunny/crossref_metadata_2025 huggingface dataset:
Sacral incidence to pubis: a novel and alternative morphologic radiological parameter to pelvic incidence in assessing spinopelvic sagittal alignment
Authors: Takahashi Yasuhito , Watanabe Kei , Okamoto Masashi , Hatsushikano Shun , Hasegawa Kazuhiro , Endo Naoto
Published: February 2021

Background

Although pelvic incidence (PI) is a key morphologic parameter in assessing spinopelvic sagittal alignment, accurate measurements of PI become difficult in patients with severe hip dislocation or femoral head deformities. This study aimed to investigate the reliability of our novel morphologic parameters and the correlations with established sagittal spinopelvic parameters.

Methods

One hundred healthy volunteers (25 male and 75 female), with an average age of 38.9 years, were analysed. Whole-body alignment in the standing position was measured using a slot-scanning X-ray imager. We measured the established spinopelvic sagittal parameters and a novel parameter: the sacral incidence to pubis (SIP). The correlation coefficient of each parameter, regression equation of PI using SIP, and regression equation of lumbar lordosis (LL) using PI or SIP were obtained. The intraclass correlation coefficient (ICC) was calculated as an evaluation of the measurement reliability.

Results

Reliability analysis showed high intra- and inter-rater agreements in all the spinopelvic parameters, with ICCs > 0.9. The SIP and pelvic inclination angle (PIA) demonstrated strong correlation with PI (R = 0.96) and pelvic tilt (PT) (R = 0.92). PI could be predicted according to the regression equation: PI = − 9.92 + 0.905 * SIP (R = 0.9596, p < 0.0001). The ideal LL could be predicted using the following equation using PI and age: ideal LL = 32.33 + 0.623 * PI – 0.280 * age (R = 0.6033, p < 0.001) and using SIP and age: ideal LL = 24.29 + 0.609 * SIP – 0.309 * age (R = 0.6177, p < 0.001).

Conclusions

Both SIP and PIA were reliable parameters for determining the morphology and orientation of the pelvis, respectively. Ideal LL was accurately predicted using the SIP with equal accuracy as the PI. Our findings will assist clinicians in the assessment of spinopelvic sagittal alignment.

Trial registration

This study was retrospectively registered with the UMIN Clinical Trials Registry (UMIN000042979; January 13, 2021).
Dermatofibrosarcoma protuberans in a young patient with epidermolysis bullosa: a case report
Authors: Bonaventura B. , Kraus D. , Stark G. B. , Fuellgraf H. , Kiefer J.
Published: February 2021

Background

Epidermolysis bullosa is a group of rare inherited skin diseases characterized by blister formation following mechanical skin trauma. Epidermolysis bullosa is associated with increased skin cancer rates, predominantly squamous cell carcinomas, yet to our best knowledge, there is no reported case of dermatofibrosarcoma protuberans in a patient with Epidermolysis bullosa.

Case presentation

Here, we present a 26-year-old man with junctional epidermolysis bullosa, who developed a DFSP on the neck. Initial, the skin alteration was mistakenly not considered malignant, which resulted in inadequate safety margins. The complete resection required a local flap to close the defect, which is not unproblematic because of the chronic inflammation and impaired healing potential of the skin due to Epidermolysis bullosa.

Conclusions

To our best knowledge, this is the first reported case of a skin-associated sarcoma in a patient with EB; however, further investigation is required to verify a correlation.
Skin AGEs and diabetic neuropathy
Authors: Papachristou Stella , Pafili Kalliopi , Papanas Nikolaos
Published: February 2021

Advanced glycation end-products (AGEs) are heterogeneous molecules produced by the non-enzymatic glycation of proteins, lipids, or nucleic acids during hyperglycaemia. Accumulation of AGEs in the peripheral nerves has recently been proposed as an additional risk factor for the development of diabetic neuropathy (DN). The gold standard for measurement of tissue-bound AGEs is tissue biopsy. However, their assessment with the newer, fast and simple method of skin autofluorescence (sAF) has recently gained special interest by virtue of its non-invasive, highly reproducible nature and its acceptable correlation with the reference method of skin biopsy. Accumulation of tissue AGEs evaluated by sAF has been shown to independently correlate with DN. Importantly, increasing evidence underscores their potential value as early biomarkers of the latter. Further important associations include diabetic nephropathy, diabetic retinopathy and cardiovascular autonomic neuropathy. However, the value of the implementation of screening with skin AGEs for DN remains unclear. The aim of the present review is to critically summarise current evidence on the association between skin AGEs and diabetic microvascular complications, with a particular emphasis on diabetic neuropathy, and to note the most important limitations of existing knowledge. Longer follow-up studies are also highly anticipated to clarify its role and provide data on patient selection and cost-effectiveness.
A challenging case of Cushing’s disease complicated with multiple thrombotic phenomena following trans-sphenoidal surgery; a case report
Authors: Wijewickrama Piyumi Sachindra Alwis , Ratnasamy Vithiya , Somasundaram Noel P. , Sumanatilleke Manilka , Ambawatte Sathyajith Buddhika
Published: February 2021

Background

Cushing’s syndrome occurs due to overproduction of cortisol from adrenal glands. Endogenous hypercortisolemia can occur secondary to adrenocorticotropic hormone (ACTH) dependent as well as independent causes. The presence of non-specific symptoms and signs contributes to a delay in diagnosis. Early identification and prompt definitive management is crucial. It is important to be alert about the post-operative complications including multiple thrombotic phenomena, which can add to the mortality. We report a case of Cushing’s disease in a young female managed with trans-sphenoidal surgery, followed by a challenging post-operative period complicated with multiple thrombotic phenomena, ultimately succumbed.

Case presentation

A 32-year-old Sri Lankan female presented with overt features of Cushing’s syndrome and diagnosed to have ACTH dependent Cushing’s disease with pituitary microadenoma. She underwent trans-sphenoidal surgery, following which she developed fatal multiple complications including diverticular rupture and ischemic colitis, needing hemicolectomy, followed by a parieto-occipital infarction.

Conclusion

This case highlights important and aggressive complications associated with Cushing’s syndrome giving rise to a challenging post-operative course. Diverticular rupture had been described in association with hypercortisolemia and this case adds to the existing literature. Post-operative ischemic colitis and stroke which contributed to the death of this patient could have been due to the procoagulant state associated with Cushing’s syndrome, with a high risk during the immediate post-operative period. This emphasizes the need to consider post-operative thromboprophylaxis in patients undergoing surgery for Cushing’s syndrome.
Integrated health Services for Children: a qualitative study of family perspectives
Authors: Satherley Rose-Marie , Lingam Raghu , Green Judith , Wolfe Ingrid
Published: February 2021

Background

There is increasing evidence that integrated care improves child related quality of life and reduces health service use. However, there is limited evidence on family perspectives about the quality of integrated care for children’s services. This study aimed to understand children, young people, and caregivers’ perceptions of a new integrated care service, and to identify essential components of integrated care for children and young people with ongoing conditions.

Methods

A qualitative analysis of in-depth interviews with caregivers and children included families (N = 37) with children with one of four ongoing conditions (asthma, eczema, epilepsy, constipation) who had experienced a new integrated care service delivered in South London, UK.

Results

Four key components of integrated services identified were: that the key health-worker understood the health needs of the family in context; that professionals involved children and caregivers in treatment; that holistic care that supported the family unit was provided; and that families experienced coordination across health, social, and education systems.

Conclusions

Children and families identify care navigation and a holistic approach as key components that make high quality integrated care services. Service developments strengthening these aspects will align well with family perspectives on what works and what matters.
TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination
Authors: Chen Jia-xin , Xu Da , Cao Jian-wei , Zuo Li , Han Zhi-tao , Tian Yi-jun , Chu Chuan-min , Zhou Wang , Pan Xiu-wu , Cui Xin-gang
Published: February 2021

Background

Renal cell carcinoma (RCC) is one of the most common malignant tumors originating from the renal parenchymal urinary epithelial system. Tripartite motif 47 (TRIM47) is a member of the TRIM family proteins, which has E3 ligase activity and has been demonstrated to be involved in the occurrence and prognosis of many tumors. The main purpose of this study is to explore the role and potential mechanism of TRIM47 in promoting malignant biological behavior of RCC.

Materials and methods

TRIM47 mRNA and protein levels in human renal cancer and paired normal adjacent tissues were detected by qRT-PCR and Western blot. The effects of TRIM47 knockdown and overexpression in renal cell carcinoma cells on cell proliferation, invasion and xenograft tumor growth in nude mice were analyzed. The molecular mechanism was explored by mass spectrometric exploration,Western blot and immunoprecipitation assays.

Results

TRIM47 promoted RCC cell proliferation in vitro and in vivo as an oncogene. Mechanistically, TRIM47 exerted an E3 ligase activity by interacting with P53 protein to increase its ubiquitination and degradation, which further promoted the malignant biological behavior of RCC.

Conclusions

Our study demonstrated that the TRIM47-P53 axis played a functional role in RCC progression and suggested a potential therapeutic target for RCC.
Understanding the roles of community health workers in improving perinatal health equity in rural Uttar Pradesh, India: a qualitative study
Authors: Blanchard Andrea K. , Ansari Shahnaz , Rajput Rajni , Colbourn Tim , Houweling Tanja A. J. , Isac Shajy , Anthony John , Prost Audrey
Published: February 2021

Background

Despite substantial reductions in perinatal deaths (stillbirths and early neonatal deaths), India’s perinatal mortality rates remain high, both nationally and in individual states. Rates are highest among disadvantaged socio-economic groups. To address this, India’s National Health Mission has trained community health workers called Accredited Social Health Activists (ASHAs) to counsel and support women by visiting them at home before and after childbirth. We conducted a qualitative study to explore the roles of ASHAs’ home visits in improving equity in perinatal health between socio-economic position groups in rural Uttar Pradesh (UP), India.

Methods

We conducted social mapping in four villages of two districts in UP, followed by three focus group discussions in each village (12 in total) with ASHAs and women who had recently given birth belonging to ‘higher’ and ‘lower’ socio-economic position groups (n = 134 participants). We analysed the data in NVivo and Dedoose using a thematic framework approach.

Results

Home visits enabled ASHAs to build trusting relationships with women, offer information about health services, schemes and preventive care, and provide practical support for accessing maternity care. This helped many women and families prepare for birth and motivated them to deliver in health facilities. In particular, ASHAs encouraged women who were poorer, less educated or from lower caste groups to give birth in public Community Health Centres (CHCs). However, women who gave birth at CHCs often experienced insufficient emergency obstetric care, mistreatment from staff, indirect costs, lack of medicines, and referrals to higher-level facilities when complications occurred. Referrals often led to delays and higher fees that placed the greatest burden on families who were considered of lower socio-economic position or living in remote areas, and increased their risk of experiencing perinatal loss.

Conclusions

The study found that ASHAs built relationships, counselled and supported many pregnant women of lower socio-economic positions. Ongoing inequities in health facility births and perinatal mortality were perpetuated by overlapping contextual issues beyond the ASHAs’ purview. Supporting ASHAs’ integration with community organisations and health system strategies more broadly is needed to address these issues and optimise pathways between equity in intervention coverage, processes and perinatal health outcomes.
Assessing additive effects of air pollutants on mortality rate in Massachusetts
Authors: Wei Yaguang , Coull Brent , Koutrakis Petros , Yang Jiabei , Li Longxiang , Zanobetti Antonella , Schwartz Joel
Published: February 2021

Background

We previously found additive effects of long- and short-term exposures to fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) on all-cause mortality rate using a generalized propensity score (GPS) adjustment approach. The study addressed an important question of how many early deaths were caused by each exposure. However, the study was computationally expensive, did not capture possible interactions and high-order nonlinearities, and omitted potential confounders.

Methods

We proposed two new methods and reconducted the analysis using the same cohort of Medicare beneficiaries in Massachusetts during 2000–2012, which consisted of 1.5 million individuals with 3.8 billion person-days of follow-up. The first method, weighted least squares (WLS), leveraged large volume of data by aggregating person-days, which gave equivalent results to the linear probability model (LPM) method in the previous analysis but significantly reduced computational burden. The second method, m-out-of-n random forests (moonRF), implemented scaling random forests that captured all possible interactions and nonlinearities in the GPS model. To minimize confounding bias, we additionally controlled relative humidity and health care utilizations that were not included previously. Further, we performed low-level analysis by restricting to person-days with exposure levels below increasingly stringent thresholds.

Results

We found consistent results between LPM/WLS and moonRF: all exposures were positively associated with mortality rate, even at low levels. For long-term PM2.5and O3, the effect estimates became larger at lower levels. Long-term exposure to PM2.5posed the highest risk: 1 μg/m3increase in long-term PM2.5was associated with 1053 (95% confidence interval [CI]: 984, 1122; based on LPM/WLS methods) or 1058 (95% CI: 988, 1127; based on moonRF method) early deaths each year among the Medicare population in Massachusetts.

Conclusions

This study provides more rigorous causal evidence between PM2.5, O3, and NO2exposures and mortality, even at low levels. The largest effect estimate for long-term PM2.5suggests that reducing PM2.5could gain the most substantial benefits. The consistency between LPM/WLS and moonRF suggests that there were not many interactions and high-order nonlinearities. In the big data context, the proposed methods will be useful for future scientific work in estimating causality on an additive scale.
Psychological experience and coping strategies of patients in the Northeast US delaying care for infertility during the COVID-19 pandemic
Authors: Seifer David B. , Petok William D. , Agrawal Alisha , Glenn Tanya L. , Bayer Arielle H. , Witt Barry R. , Burgin Blair D. , Lieman Harry J.
Published: February 2021

Background

On March 17, 2020 an expert ASRM task force recommended the temporary suspension of new, non-urgent fertility treatments during an ongoing world-wide pandemic of Covid-19. We surveyed at the time of resumption of fertility care the psychological experience and coping strategies of patients pausing their care due to Covid-19 and examined which factors were associated and predictive of resilience, anxiety, stress and hopefulness.

Methods

Cross sectional cohort patient survey using an anonymous, self-reported, single time, web-based, HIPPA compliant platform (REDCap). Survey sampled two Northeast academic fertility practices (Yale Medicine Fertility Center in CT and Montefiore’s Institute for Reproductive Medicine and Health in NY). Data from multiple choice and open response questions collected demographic, reproductive history, experience and attitudes about Covid-19, prior infertility treatment, sense of hopefulness and stress, coping strategies for mitigating stress and two validated psychological surveys to assess anxiety (six-item short-form State Trait Anxiety Inventory (STAl-6)) and resilience (10-item Connor-Davidson Resilience Scale, (CD-RISC-10).

Results

Seven hundred thirty-four patients were sent invitations to participate. Two hundred fourteen of 734 (29.2%) completed the survey. Patients reported their fertility journey had been delayed a mean of 10 weeks while 60% had been actively trying to conceive > 1.5 years. The top 5 ranked coping skills from a choice of 19 were establishing a daily routine, going outside regularly, exercising, maintaining social connection via phone, social media or Zoom and continuing to work. Having a history of anxiety (p < 0.0001) and having received oral medication as prior infertility treatment (p < 0.0001) were associated with lower resilience. Increased hopefulness about having a child at the time of completing the survey (p < 0.0001) and higher resilience scores (p < 0.0001) were associated with decreased anxiety. Higher reported stress scores (p < 0.0001) were associated with increased anxiety. Multiple multivariate regression showed being non-Hispanic black (p = 0.035) to be predictive of more resilience while variables predictive of less resilience were being a full-time homemaker (p = 0.03), having received oral medication as prior infertility treatment (p = 0.003) and having higher scores on the STAI-6 (< 0.0001).

Conclusions

Prior to and in anticipation of further pauses in treatment the clinical staff should consider pretreatment screening for psychological distress and provide referral sources. In addition, utilization of a patient centered approach to care should be employed.
Plasmatic and cell-based enhancement by microparticles originated from platelets and endothelial cells under simulated in vitro conditions of a dilutional coagulopathy
Authors: Böhm Julia K. , Schäfer Nadine , Maegele Marc , Stümpges Birgit , Bauerfeind Ursula , Caspers Michael
Published: February 2021

Background

Aggressive fluid management and other external factors may lead to hypothermia, acidosis and hemodilution (defined as Lethal Triad, LT) contributing to a trauma-induced coagulopathy (TIC) that worsens patients’ outcomes. Procoagulant microparticles (MP) are crucial players at the interface of cellular and plasmatic coagulation. However, their functions remain largely unexplored. This study aimed to characterize effects of MP subtypes and concentrations on functional coagulation under in vitro simulated conditions.

Methods

Blood from eleven volunteers were collected to simulate in vitro conditions of hemodilution (HD) and LT, respectively. HD was induced by replacing a blood volume of 33% by crystalloids and for LT, samples were further processed by reducing the temperature to 32 °C and lowering the pH to 6.8. MP were obtained either from platelet concentrates (platelet-derived MP, PDMP) or from cell culture (ECV304 cells for endothelial-derived MP, EDMP) by targeted stimulation. After introducing MP to in vitro conditions, we measured their concentration-dependent effects (1.000, 10.000 and 15.000 MP/μl blood) on coagulation compared to whole blood (WB). For each condition, coagulation was characterized by flow cytometric platelet activation and by quantification of fibrin clot propagation using Thrombodynamics® technology.

Results

MP originated from platelets and endothelial cells affected blood coagulation in a concentration-dependent manner. Particularly, high PDMP quantities (10.000 and 15.000 PDMP/μl blood) significantly induced platelet activation and fibrin clot growth and size in HD conditions. In LT conditions as well, only high PDMP concentration induced platelet activation, clot growth and size. In contrast, EDMP did not induce platelet activation, but resulted in enhanced formation of spontaneous clots, irrespective of simulated condition. With increasing EDMP concentration, the time until the onset of spontaneous clotting decreased in both HD and LT conditions.

Discussion

The study demonstrates an essential role of MP within the coagulation process under simulated coagulopathic conditions. PDMP affected platelets promoting clot formation likely by providing a surface enlargement. EDMP presumably affected clotting factors of the plasmatic coagulation resulting in an increased formation of spontaneous clots.

Conclusion

Under simulated conditions of a dilutional coagulopathy, MP from different cellular origin indicate a divergent but both procoagulant mechanism within the coagulation process.
Drug dosing in the critically ill obese patient: a focus on medications for hemodynamic support and prophylaxis
Authors: Erstad Brian L. , Barletta Jeffrey F.
Published: February 2021

Medications used for supportive care or prophylaxis constitute a significant portion of drug utilization in the intensive care unit. Evidence-based guidelines are available for many aspects of supportive care but drug doses listed are typically for patients with normal body habitus and not morbid obesity. Failure to account for the pharmacokinetic changes that occur with obesity can lead to an incorrect dose and treatment failure or toxicity. This paper is intended to help clinicians design initial dosing regimens in critically ill obese patients for medications commonly used for hemodynamic support or prophylaxis. A detailed literature search of medications used for supportive care or prophylaxis listed in practice guidelines was conducted with an emphasis on obesity, pharmacokinetics and dosing. Relevant manuscripts were reviewed and strategies for dosing are provided. For medications used for hemodynamic support, a similar strategy can be used as in non-obese patients. Similarly, medications for stress ulcer prophylaxis do not need to be adjusted. Anticoagulants for venous thromboembolism prophylaxis, on the other hand, require an individualized approach where higher doses are necessary.
Acetate as substrate for l-malic acid production with Aspergillus oryzae DSM 1863
Authors: Kövilein Aline , Umpfenbach Julia , Ochsenreither Katrin
Published: February 2021

Background

Microbial malic acid production is currently not able to compete economically with well-established chemical processes using fossil resources. The utilization of inexpensive biomass-based substrates containing acetate could decrease production costs and promote the development of microbial processes. Acetate is a by-product in lignocellulosic hydrolysates and fast pyrolysis products or can be synthesized by acetogens during syngas fermentation. For the fermentation of these substrates, a robust microorganism with a high tolerance for biomass-derived inhibitors is required. Aspergillus oryzae is a suitable candidate due to its high tolerance and broad substrate spectrum. To pave the path towards microbial malic acid production, the potential of acetate as a carbon source for A. oryzae is evaluated in this study.

Results

A broad acetate concentration range was tested both for growth and malic acid production with A. oryzae. Dry biomass concentration was highest for acetic acid concentrations of 40–55 g/L reaching values of about 1.1 g/L within 48 h. Morphological changes were observed depending on the acetate concentration, yielding a pellet-like morphology with low and a filamentous structure with high substrate concentrations. For malic acid production, 45 g/L acetic acid was ideal, resulting in a product concentration of 8.44 ± 0.42 g/L after 192 h. The addition of 5–15 g/L glucose to acetate medium proved beneficial by lowering the time point of maximum productivity and increasing malic acid yield. The side product spectrum of cultures with acetate, glucose, and cultures containing both substrates was compared, showing differences especially in the amount of oxalic, succinic, and citric acid produced. Furthermore, the presence of CaCO3, a pH regulator used for malate production with glucose, was found to be crucial also for malic acid production with acetate.

Conclusions

This study evaluates relevant aspects of malic acid production with A. oryzae using acetate as carbon source and demonstrates that it is a suitable substrate for biomass formation and acid synthesis. The insights provided here will be useful to further microbial malic acid production using renewable substrates.
Melatonin levels in the Alzheimer’s disease continuum: a systematic review
Authors: Nous Amber , Engelborghs Sebastiaan , Smolders Ilse
Published: February 2021

Background

The search for new Alzheimer’s disease (AD) cerebrospinal fluid (CSF) and blood biomarkers with potential pathophysiological and clinical relevance continues, as new biomarkers might lead to improved early and differential diagnosis, monitoring of disease progression and might even identify new druggable targets. Melatonin might be an interesting biomarker as an inverse correlation between CSF melatonin levels, and severity of the neuropathology as measured by Braak stages has been described. Melatonin can be measured in different body fluids, such as CSF, blood, saliva and urine.

Objectives

The aim of this systematic review was to review all available studies regarding melatonin levels in different body fluids in the AD continuum and give an extensive overview of reported outcomes.

Methods

We included papers comparing melatonin levels between healthy controls and human patients belonging to the AD continuum. A systematic search of PubMed and Web of Science led to inclusion of 20 full-length English papers following exclusion of duplicates.

Results

This systematic literature search showed that disruptions in melatonin levels occur with age, but also in AD when compared to age-matched controls. Night-time melatonin levels were found to be lower in CSF and blood of AD patients as compared to controls. Literature was not conclusive regarding alterations in blood daytime melatonin levels or regarding saliva melatonin in AD patients. Decreased total and night-time melatonin production has been described in urine of AD patients.

Conclusion

Our systematic review shows evidence for disruptions in (night-time) melatonin levels in AD as compared to age-matched controls. Although more studies are needed to understand the contribution of disruption of the melatonergic system to the pathophysiology of AD, the potential anti-AD effects that have been attributed to melatonin, renders research on this topic relevant for the discovery of potential future treatment effects of melatonin for AD. The use of melatonin as potential blood biomarker for disease progression should also be further investigated.
Discovery of novel community-relevant small proteins in a simplified human intestinal microbiome
Authors: Petruschke Hannes , Schori Christian , Canzler Sebastian , Riesbeck Sarah , Poehlein Anja , Daniel Rolf , Frei Daniel , Segessemann Tina , Zimmerman Johannes , Marinos Georgios , Kaleta Christoph , Jehmlich Nico , Ahrens Christian H. , von Bergen Martin
Published: February 2021

Background

The intestinal microbiota plays a crucial role in protecting the host from pathogenic microbes, modulating immunity and regulating metabolic processes. We studied the simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species with a particular focus on the discovery of novel small proteins with less than 100 amino acids (= sProteins), some of which may contribute to shape the simplified human intestinal microbiota. Although sProteins carry out a wide range of important functions, they are still often missed in genome annotations, and little is known about their structure and function in individual microbes and especially in microbial communities.

Results

We created a multi-species integrated proteogenomics search database (iPtgxDB) to enable a comprehensive identification of novel sProteins. Six of the eight SIHUMIx species, for which no complete genomes were available, were sequenced and de novo assembled. Several proteomics approaches including two earlier optimized sProtein enrichment strategies were applied to specifically increase the chances for novel sProtein discovery. The search of tandem mass spectrometry (MS/MS) data against the multi-species iPtgxDB enabled the identification of 31 novel sProteins, of which the expression of 30 was supported by metatranscriptomics data. Using synthetic peptides, we were able to validate the expression of 25 novel sProteins. The comparison of sProtein expression in each single strain versus a multi-species community cultivation showed that six of these sProteins were only identified in the SIHUMIx community indicating a potentially important role of sProteins in the organization of microbial communities. Two of these novel sProteins have a potential antimicrobial function. Metabolic modelling revealed that a third sProtein is located in a genomic region encoding several enzymes relevant for the community metabolism within SIHUMIx.

Conclusions

We outline an integrated experimental and bioinformatics workflow for the discovery of novel sProteins in a simplified intestinal model system that can be generically applied to other microbial communities. The further analysis of novel sProteins uniquely expressed in the SIHUMIx multi-species community is expected to enable new insights into the role of sProteins on the functionality of bacterial communities such as those of the human intestinal tract.
Improvement in resolution of fiber-laser photoacoustic tomography based on a virtual-point concept
Authors: Bai Xue , Li Xu , Ma Jun , Guan Bai-Ou
Published: February 2021

In this study, a virtual-point concept was introduced into fiber-laser photoacoustic tomography to improve the elevational image resolution. The flexible fiber laser was bent into an arc shape to conform to the ultrasound wavefront, which formed an ultrasound focus at the center of the arc. The synthetic aperture focusing technique was utilized to reconstruct the images; as a result, the elevational resolution particularly within the out-of-focus region was considerably improved compared to the resolution of an image retrieved by multiplexing the PA time-resolved signals with sound velocity. The all-optical fiber-laser photoacoustic tomography system with a high spatial resolution has potential for various applications, including biomedical research and preclinical/clinical diagnosis.
High Prevalence of Weight Gain in Childhood Brain Tumor Survivors and Its Association With Hypothalamic-Pituitary Dysfunction
Authors: van Schaik Jiska , van Roessel Ichelle M. A. A. , Schouten-van Meeteren Netteke A. Y. N. , van Iersel Laura , Clement Sarah C. , Boot Annemieke M. , Claahsen-van der Grinten Hedi L. , Fiocco Marta , Janssens Geert O. , van Vuurden Dannis G. , Michiels Erna M. , Han Sen K. S. , van Trotsenburg Paul A. S. P. , Vandertop Peter W. P. , Kremer Leontien C. M. , van Santen Hanneke M.
Published: February 2021

PURPOSE

Childhood brain tumor survivors (CBTS) are at risk for developing obesity, which negatively influences cardiometabolic health. The prevalence of obesity in CBTS may have been overestimated in previous cohorts because of inclusion of children with craniopharyngioma. On the contrary, the degree of weight gain may have been underestimated because of exclusion of CBTS who experienced weight gain, but were neither overweight nor obese. Weight gain may be an indicator of underlying hypothalamic-pituitary (HP) dysfunction. We aimed to study prevalence of and risk factors for significant weight gain, overweight, or obesity, and its association with HP dysfunction in a national cohort of noncraniopharyngioma and nonpituitary CBTS.

METHODS

Prevalence of and risk factors for significant weight gain (body mass index [BMI] change ≥ +2.0 standard deviation score [SDS]), overweight, or obesity at follow-up, and its association with HP dysfunction were studied in a nationwide cohort of CBTS, diagnosed in a 10-year period (2002-2012), excluding all craniopharyngioma and pituitary tumors.

RESULTS

Of 661 CBTS, with a median age at follow-up of 7.3 years, 33.1% had significant weight gain, overweight, or obesity. Of the CBTS between 4 and 20 years of age, 28.7% were overweight or obese, compared with 13.2% of the general population between 4 and 20 years of age. BMI SDS at diagnosis, diagnosis of low-grade glioma, diabetes insipidus, and central precocious puberty were associated with weight gain, overweight, or obesity. The prevalence of HP dysfunction was higher in overweight and obese CTBS compared with normal-weight CBTS.

CONCLUSION

Overweight, obesity, and significant weight gain are prevalent in CBTS. An increase in BMI during follow-up may be a reflection of HP dysfunction, necessitating more intense endocrine surveillance.
Hyperoxia-induced bronchopulmonary dysplasia: better models for better therapies
Authors: Giusto Kiersten , Wanczyk Heather , Jensen Todd , Finck Christine
Published: February 2021

Bronchopulmonary dysplasia (BPD) is a chronic lung disease caused by exposure to high levels of oxygen (hyperoxia) and is the most common complication that affects preterm newborns. At present, there is no cure for BPD. Infants can recover from BPD; however, they will suffer from significant morbidity into adulthood in the form of neurodevelopmental impairment, asthma and emphysematous changes of the lung. The development of hyperoxia-induced lung injury models in small and large animals to test potential treatments for BPD has shown some success, yet a lack of standardization in approaches and methods makes clinical translation difficult. In vitro models have also been developed to investigate the molecular pathways altered during BPD and to address the pitfalls associated with animal models. Preclinical studies have investigated the efficacy of stem cell-based therapies to improve lung morphology after damage. However, variability regarding the type of animal model and duration of hyperoxia to elicit damage exists in the literature. These models should be further developed and standardized, to cover the degree and duration of hyperoxia, type of animal model, and lung injury endpoint, to improve their translational relevance. The purpose of this Review is to highlight concerns associated with current animal models of hyperoxia-induced BPD and to show the potential of in vitro models to complement in vivo studies in the significant improvement to our understanding of BPD pathogenesis and treatment. The status of current stem cell therapies for treatment of BPD is also discussed. We offer suggestions to optimize models and therapeutic modalities for treatment of hyperoxia-induced lung damage in order to advance the standardization of procedures for clinical translation.
Modified chromosome structure caused by phosphomimetic H2A modulates the DNA damage response by increasing chromatin mobility in yeast
Authors: García Fernández Fabiola , Lemos Brenda , Khalil Yasmine , Batrin Renaud , Haber James E. , Fabre Emmanuelle
Published: February 2021

In budding yeast and mammals, double-strand breaks (DSBs) trigger global chromatin mobility together with rapid phosphorylation of histone H2A over an extensive region of the chromatin. To assess the role of H2A phosphorylation in this response to DNA damage, we have constructed strains where H2A has been mutated to the phosphomimetic H2A-S129E. We show that mimicking H2A phosphorylation leads to an increase in global chromatin mobility in the absence of DNA damage. The intrinsic chromatin mobility of H2A-S129E is not due to downstream checkpoint activation, histone degradation or kinetochore anchoring. Rather, the increased intrachromosomal distances observed in the H2A-S129E mutant are consistent with chromatin structural changes. Strikingly, in this context the Rad9-dependent checkpoint becomes dispensable. Moreover, increased chromatin dynamics in the H2A-S129E mutant correlates with improved DSB repair by non-homologous end joining and a sharp decrease in interchromosomal translocation rate. We propose that changes in chromosomal conformation due to H2A phosphorylation are sufficient to modulate the DNA damage response and maintain genome integrity.

This article has an associated First Person interview with the first author of the paper.
Interest Rate Volatility and No-Arbitrage Affine Term Structure Models
Authors: Joslin Scott , Le Anh
Published: February 2021

Within the affine framework, many have observed a tension between matching conditional first and second moments in dynamic term structure models (DTSMs). Although the existence of this tension is generally accepted, less understood is the mechanism that underlies it. We show that no arbitrage along with the rich information in the cross section of yields has strong implications for both the dynamics of volatility and the forecasts of yields. We show that this link implied by the absence of arbitrage—and not the factor structure per se—underlies the tension between first and second moments found in the literature. Adding to recent research that has suggested that no-arbitrage restrictions are nearly irrelevant in Gaussian DTSMs, our results show that no-arbitrage restrictions are potentially relevant when there is stochastic volatility.

This paper was accepted by Gustavo Manso, finance.
A Study of Convex Convex-Composite Functions via Infimal Convolution with Applications
Authors: Burke James V. , Tim Hoheisel , Nguyen Quang V.
Published: February 2021

In this paper, we provide a full conjugacy and subdifferential calculus for convex convex-composite functions in finite-dimensional space. Our approach, based on infimal convolution and cone convexity, is straightforward. The results are established under a verifiable Slater-type condition, with relaxed monotonicity and without lower semicontinuity assumptions on the functions in play. The versatility of our findings is illustrated by a series of applications in optimization and matrix analysis, including conic programming, matrix-fractional, variational Gram, and spectral functions.
Technical Note—Bootstrap-based Budget Allocation for Nested Simulation
Authors: Zhang Kun , Liu Guangwu , Wang Shiyu
Published: February 2021

Nested simulation (also referred to as two-level simulation) finds a variety of applications such as financial risk measurement, and a central issue of nested simulation is how to allocate a finite amount of simulation budget to achieve the highest accuracy. In “Bootstrap-based Budget Allocation for Nested Simulation”, Zhang, Liu, and Wang propose a bootstrap-based rule for simulation budget allocation for nested simulation. By utilizing the asymptotically optimal inner- and outer-level sample sizes that are typically unknown, the proposed method employs bootstrap sampling on a small amount of initial samples to estimate the unknown optimal sample sizes, thus providing a reasonably good allocation rule for the main simulation. An allocation rule to ensure the asymptotic validity of confidence intervals is also given.
RESOURCE REVIEW
Authors: Cousins Emily
Published: February 2021

Emily Cousins continues our new resource review column, which will provide a synopsis and brief analysis of a recently published resource that may be of interest to neuroscience nurses; a full reference is provided for those who wish to read the text
Factors affecting health-related quality of life among Nepalese adults with mild traumatic brain injury
Authors: Aryal Shristi , Thosingha Orapan , Chayaput Prangtip
Published: February 2021

Background:

Mild traumatic brain injury (MTBI) is a stressful life event. Most patients recover, but a subset of patients experience somatic, cognitive and behavioural symptoms that affect health-related quality of life (HRQOL).

Aims:

To identify the level impact on HRQOL and to examine the associated factors of HRQOL among patients with MTBI.

Methods:

This was a correlational predictive study.

Findings:

The mean age of the participants was 33.89 years, with a range from 18 to 62 years. HRQOL was at amoderate level. In multiple regression analysis, social support (β = .419, p = .000), PCS severity (β = -.245, p = .003) and economic status (β = .167, p = .035) accounted for 36.3% of explained variance on HRQOL.

Conclusions:

Post-concussion symptoms after discharge should be evaluated, and patients' need for support must be thoroughly assessed.
What is new for neurology in 2021?
Authors: Thomas Sue
Published: February 2021

At a time when the COVID-19 pandemic is having a significant impact on neurology services, Sue Thomas delves into the recently published National Institute for Health and Care Excellence Quality Standards for Suspected Neurological Conditions and highlights the anticipated Getting It Right First Time neurology final report.
RESEARCH ROUNDUP
Authors: Dening Karen Harrison
Published: February 2021

Karen Harrison Dening provides a synopsis and brief review of a selection of recently published research articles that are of interest to neuroscience nurses, highlighting key points to keep you up to date; a full reference is provided for those who wish to read the research in more detail
A tale of two fish: Comparative transcriptomics of resistant and susceptible steelhead following exposure to Ceratonova shasta highlights differences in parasite recognition
Authors: Barrett Damien E. , Bartholomew Jerri L.
Published: February 2021

Diseases caused by myxozoan parasites represent a significant threat to the health of salmonids in both the wild and aquaculture setting, and there are no effective therapeutants for their control. The myxozoanCeratonova shastais an intestinal parasite of salmonids that causes severe enteronecrosis and mortality. Most fish populations appear genetically fixed as resistant or susceptible to the parasite, offering an attractive model system for studying the immune response to myxozoans. We hypothesized that early recognition of the parasite is a critical factor driving resistance and that susceptible fish would have a delayed immune response. RNA-seq was used to identify genes that were differentially expressed in the gills and intestine during the early stages ofC.shastainfection in both resistant and susceptible steelhead (Oncorhynchus mykiss). This revealed a downregulation of genes involved in the IFN-γ signaling pathway in the gills of both phenotypes. Despite this, resistant fish quickly contained the infection and several immune genes, including two innate immune receptors were upregulated. Susceptible fish, on the other hand, failed to control parasite proliferation and had no discernible immune response to the parasite, including a near-complete lack of differential gene expression in the intestine. Further sequencing of intestinal samples from susceptible fish during the middle and late stages of infection showed a vigorous yet ineffective immune response driven by IFN-γ, and massive differential expression of genes involved in cell adhesion and the extracellular matrix, which coincided with the breakdown of the intestinal structure. Our results suggest that the parasite may be suppressing the host’s immune system during the initial invasion, and that susceptible fish are unable to recognize the parasite invading the intestine or mount an effective immune response. These findings improve our understanding of myxozoan-host interactions while providing a set of putative resistance markers for future studies.
Combination of ipratropium bromide and salbutamol in children and adolescents with asthma: A meta-analysis
Authors: Xu Hongzhen , Tong Lin , Gao Peng , Hu Yan , Wang Huijuan , Chen Zhimin , Fang Luo
Published: February 2021

Background

A combination of ipratropium bromide (IB) and salbutamol is commonly used to treat asthma in children and adolescents; however, there has been a lack of consistency in its usage in clinical practice.

Objective

To evaluate the efficacy and safety of IB + salbutamol in the treatment of asthma in children and adolescents.

Methods

The MEDLINE, Embase, and Cochrane Library as well as other Chinese biomedical databases (including China Biological Medicine Database, Chinese National Knowledge Infrastructure, Chongqing VIP, and Wanfang Chinese language bibliographic database) were systematically searched from the earliest record date to September 2020 for randomized controlled trials in children and adolescents (≤18 years) with asthma who received IB + salbutamol or salbutamol alone. The primary outcomes included hospital admission and adverse events. A random effects model with a 95% confidence interval (CI) was used. Subgroup analysis was performed according to age, severity of asthma, and co-interventions with other asthma controllers. This study was registered with PROSPERO.

Results

Of the 1061 studies that were identified, 55 met the inclusion criteria and involved 6396 participants. IB + salbutamol significantly reduced the risk of hospital admission compared with salbutamol alone (risk ratio [RR] 0.79; 95% CI 0.66–0.95; p = 0.01; I2 = 40%). Subgroup analysis only showed significant difference in the risk of hospital admission in participants with severe asthma exacerbation (RR 0.73; 95% CI 0.60–0.88; p = 0.0009; I2 = 4%) and moderate-to-severe exacerbation (RR 0.69; 95% CI 0.50–0.96; p = 0.03; I2 = 3%). There were no significant differences in the risk of adverse events between IB + salbutamol group and salbutamol alone group (RR 1.77; 95% CI 0.63–4.98).

Conclusion

IB + salbutamol may be more effective than salbutamol alone for the treatment of asthma in children and adolescents, especially in those with severe and moderate to severe asthma exacerbation. The very low to high quality of evidence indicated that future well-designed double-blind RCTs with large sample are needed for research on evaluating the effectiveness of IB + salbutamol treatment for asthma in children and adolescents.
Relationships of capsular polysaccharides belonging to Campylobacter jejuni HS1 serotype complex
Authors: Monteiro Mario A. , Chen Yu-Han , Ma Zuchao , Ewing Cheryl P. , Mohamad Nor Nooraisyah , Omari Eman , Song Ellen , Gabryelski Pawel , Guerry Patricia , Poly Frédéric
Published: February 2021

The Campylobacter jejuni capsule type HS1 complex is one of the most common serotypes identified worldwide, and consists of strains typing as HS1, HS1/44, HS44 and HS1/8. The capsule structure of the HS1 type strain was shown previously to be composed of teichoic-acid like glycerol-galactosyl phosphate repeats [4-)-α-D-Galp-(1–2)-Gro-(1-P-] with non-stoichiometric fructose branches at the C2 and C3 of Gal and non-stoichiometric methyl phosphoramidate (MeOPN) modifications on the C3 of the fructose. Here, we demonstrate that the capsule of an HS1/44 strain is identical to that of the type strain of HS1, and the capsule of HS1/8 is also identical to HS1, except for an additional site of MeOPN modification at C6 of Gal. The DNA sequence of the capsule locus of an HS44 strain included an insertion of 10 genes, and the strain expressed two capsules, one identical to the HS1 type strain, but with no fructose branches, and another composed of heptoses and MeOPN. We also characterize a HS1 capsule biosynthesis gene, HS1.08, as a fructose transferase responsible for the attachment of the β-D-fructofuranoses residues at C2 and C3 of the Gal unit. In summary, the common component of all members of the HS1 complex is the teichoic-acid like backbone that is likely responsible for the observed sero-cross reactivity.