bluuebunny/crossref_metadata_2025 huggingface dataset:
NEK1 deficiency affects mitochondrial functions and the transcriptome of key DNA repair pathways
Authors: Martins Mariana Bonjiorno , Perez Arina Marina , Bohr Vilhelm A , Wilson David M , Kobarg Jörg
Published: March 2021

Previous studies have indicated important roles for NIMA-related kinase 1 (NEK1) in modulating DNA damage checkpoints and DNA repair capacity. To broadly assess the contributions of NEK1 to genotoxic stress and mitochondrial functions, we characterised several relevant phenotypes of NEK1 CRISPR knockout (KO) and wild-type (WT) HAP1 cells. Our studies revealed that NEK1 KO cells resulted in increased apoptosis and hypersensitivity to the alkylator methyl methanesulfonate, the radiomimetic bleomycin and UVC light, yet increased resistance to the crosslinker cisplatin. Mitochondrial functionalities were also altered in NEK1 KO cells, with phenotypes of reduced mitophagy, increased total mitochondria, elevated levels of reactive oxygen species, impaired complex I activity and higher amounts of mitochondrial DNA damage. RNA-seq transcriptome analysis coupled with quantitative real-time PCR studies comparing NEK1 KO cells with NEK1 overexpressing cells revealed that the expression of genes involved in DNA repair pathways, such as base excision repair, nucleotide excision repair and double-strand break repair, are altered in a way that might influence genotoxin resistance. Together, our studies underline and further support that NEK1 serves as a hub signalling kinase in response to DNA damage, modulating DNA repair capacity, mitochondrial activity and cell fate determination.
Escherichia coliRNase E can efficiently replace RNase Y inBacillus subtilis
Authors: Laalami Soumaya , Cavaiuolo Marina , Roque Sylvain , Chagneau Carine , Putzer Harald
Published: March 2021

RNase Y and RNase E are disparate endoribonucleases that govern global mRNA turnover/processing in the two evolutionary distant bacteria Bacillus subtilis and Escherichia coli, respectively. The two enzymes share a similar in vitro cleavage specificity and subcellular localization. To evaluate the potential equivalence in biological function between the two enzymes in vivo we analyzed whether and to what extent RNase E is able to replace RNase Y in B. subtilis. Full-length RNase E almost completely restores wild type growth of the rny mutant. This is matched by a surprising reversal of transcript profiles both of individual genes and on a genome-wide scale. The single most important parameter to efficient complementation is the requirement for RNase E to localize to the inner membrane while truncation of the C-terminal sequences corresponding to the degradosome scaffold has only a minor effect. We also compared the in vitro cleavage activity for the major decay initiating ribonucleases Y, E and J and show that no conclusions can be drawn with respect to their activity in vivo. Our data confirm the notion that RNase Y and RNase E have evolved through convergent evolution towards a low specificity endonuclease activity universally important in bacteria.
Central bank purchases of sovereign bonds in the euro area, the random walk hypothesis, and different measures of risk
Authors: Belke Ansgar , Gros Daniel , Shamsfakhr Farzaneh
Published: March 2021

The large purchase of public sector bonds (PSPP) by the ECB constitutes an interesting special case of quantitative easing (QE). It involved the purchase of risky, peripheral euro area government bonds—not by the ECB itself but by the national central banks at their own risk. The PSPP can be assimilated into a buy-back financed with senior debt, which should reduce the value of the remaining debt. Theory thus suggests that the PSPP should not be expected to have a positive impact on peripheral risk spreads. Empirical studies try to measure the impact of the asset purchases of central banks (QE) using the market reaction at the announcement date. The announcement effects are taken to be permanent because long-term rates are assumed to follow a random walk. We show that this assumption is not warranted for the risk spreads on bonds or the credit default swaps of peripheral euro area countries.
The Science Behind Safe School Re-opening: Leveraging the Pillars of Infection Control to Support Safe Elementary and Secondary Education During the COVID-19 Pandemic
Authors: Schechter-Perkins Elissa M , van den Berg Polly , Branch-Elliman Westyn
Published: March 2021

There are limited tools for adapting coronavirus disease 2019 (COVID-19) infection control plans to school settings. We present an infection prevention model for optimizing safe re-opening for elementary and secondary schools during the global COVID-19 pandemic and review the current evidence behind various infection prevention interventions in school settings. The model is adapted from the Centers for Disease Control and Prevention fundamental pillars for infection prevention and includes 4 categories of intervention: epidemiologic controls (town prevalence metrics, diagnostic testing, quarantine strategies), administrative controls (state vaccination policies, alternative school models, symptom screens, quarantine breaks), engineering/environmental controls (distancing, outdoor space, ventilation), and personal protective equipment (PPE)/hand hygiene (face coverings, hand sanitizing).

The adapted infection control pillars model utilizes implementation science–informed considerations to maximize pragmatism and adherence by leveraging evidence-based strategies. It highlights the necessity of redundant infection prevention interventions, acknowledges the importance of community buy-in to achieve real-world effectiveness, and addresses tactics to overcome implementation barriers. Recommendations are grounded in the Dynamic Sustainability Framework and include suggestions to maintain infection prevention effectiveness over time to ensure ongoing safety.
Three-Dimensional-Printed Drill Guides for Occipitothoracic Fusion in a Pediatric Patient With Occipitocervical Instability
Authors: Pijpker Peter A J , Kuijlen Jos M A , Kaptein Bart L , Pondaag Willem
Published: March 2021

BACKGROUND

Pediatric occipitothoracic fusion can be challenging because of small size pedicles and thin occipital bone. Three-dimensional (3D) printing technology can help with accurate screw insertion but has not been described for occipital keel plate positioning so far.

OBJECTIVE

To describe the novel use of 3D technology to position occipital keel plates during pediatric occipitothoracic fixation.

METHODS

A young boy with segmental spinal dysgenesis presented with asymmetrical pyramidal paresis in all limbs. Developmental abnormities of the cervical spine caused a thinned spinal cord, and because of progressive spinal cord compression, surgical intervention by means of occipitothoracic fixation was indicated at the age of 3 yr.

Because of the small-size pedicles and thin occipital bone, the pedicle screws and occipital plates were planned meticulously using 3D virtual surgical planning technology. The rods were virtually bent in order to properly align with the planned screws. By means of 3D-printed guides, the surgical plan was transferred to the operating theater. For the occipital bone, a novel guide concept was developed, aiming for screw positions at maximal bone thickness.

RESULTS

The postoperative course was uneventful, and radiographs showed good cervical alignment. After superimposing the virtual plan with the intraoperative acquired computed tomography, it was confirmed that the occipital plate positions matched the virtual plan and that pedicle screws were accurately inserted without signs of breach.

CONCLUSION

The use of 3D technology has greatly facilitated the performance of the occipitothoracic fixation and could, in the future, contribute to safer pediatric spinal fixation procedures.
Plankton food webs in the oligotrophic Gulf of Mexico spawning grounds of Atlantic bluefin tuna
Authors: Stukel Michael R , Gerard Trika , Kelly Thomas B , Knapp Angela N , Laiz-Carrión Raúl , Lamkin John T , Landry Michael R , Malca Estrella , Selph Karen E , Shiroza Akihiro , Shropshire Taylor A , Swalethorp Rasmus
Published: March 2021

We used linear inverse ecosystem modeling techniques to assimilate data from extensive Lagrangian field experiments into a mass-balance constrained food web for the Gulf of Mexico open-ocean ecosystem. This region is highly oligotrophic, yet Atlantic bluefin tuna (ABT) travel long distances from feeding grounds in the North Atlantic to spawn there. Our results show extensive nutrient regeneration fueling primary productivity (mostly by cyanobacteria and other picophytoplankton) in the upper euphotic zone. The food web is dominated by the microbial loop (>70% of net primary productivity is respired by heterotrophic bacteria and protists that feed on them). By contrast, herbivorous food web pathways from phytoplankton to metazoan zooplankton process <10% of the net primary production in the mixed layer. Nevertheless, ABT larvae feed preferentially on podonid cladocerans and other suspension-feeding zooplankton, which in turn derive much of their nutrition from nano- and micro-phytoplankton (mixotrophic flagellates, and to a lesser extent, diatoms). This allows ABT larvae to maintain a comparatively low trophic level (~4.2 for preflexion and postflexion larvae), which increases trophic transfer from phytoplankton to larval fish.
Functional characterization of proton antiport regulation in the thylakoid membrane
Authors: Uflewski Michał , Mielke Sarah , Correa Galvis Viviana , von Bismarck Thekla , Chen Xiaoheng , Tietz Enrico , Ruß Jeremy , Luzarowski Marcin , Sokolowska Ewelina , Skirycz Aleksandra , Eirich Jürgen , Finkemeier Iris , Schöttler Mark Aurel , Armbruster Ute
Published: March 2021

During photosynthesis, energy is transiently stored as an electrochemical proton gradient across the thylakoid membrane. The resulting proton motive force (pmf) is composed of a membrane potential (ΔΨ) and a proton concentration gradient (ΔpH) and powers the synthesis of ATP. Light energy availability for photosynthesis can change very rapidly and frequently in nature. Thylakoid ion transport proteins buffer the effects that light fluctuations have on photosynthesis by adjusting pmf and its composition. Ion channel activities dissipate ΔΨ, thereby reducing charge recombinations within photosystem II. The dissipation of ΔΨ allows for increased accumulation of protons in the thylakoid lumen, generating the signal that activates feedback downregulation of photosynthesis. Proton export from the lumen via the thylakoid K+ exchange antiporter 3 (KEA3), instead, decreases the ΔpH fraction of the pmf and thereby reduces the regulatory feedback signal. Here, we reveal that the Arabidopsis (Arabidopsis thaliana) KEA3 protein homo-dimerizes via its C-terminal domain. This C-terminus has a regulatory function, which responds to light intensity transients. Plants carrying a C-terminus-less KEA3 variant show reduced feed-back downregulation of photosynthesis and suffer from increased photosystem damage under long-term high light stress. However, during photosynthetic induction in high light, KEA3 deregulation leads to an increase in carbon fixation rates. Together, the data reveal a trade-off between long-term photoprotection and a short-term boost in carbon fixation rates, which is under the control of the KEA3 C-terminus.
Incidence of Paget’s disease of bone in the UK: evidence of a continuing decline
Authors: Cook Michael J , Pye Stephen R , Lunt Mark , Dixon William G , Ashcroft Darren M , O’Neill Terence W
Published: March 2021

Objectives

To characterize the incidence of clinically diagnosed Paget’s disease of bone in the UK during 1999–2015 and to determine variations in the incidence of disease by age, sex, geography and level of deprivation.

Methods

Incident cases of Paget’s disease occurring between 1999 and 2015 were identified from primary care records. Overall crude incidence and incidence stratified by age and sex was calculated each year from 1999 to 2015. Direct age- and sex-standardized incidence was also calculated. We used Poisson regression to look at variations in incidence by deprivation and UK region.

Results

A total of 3592 incident cases of Paget’s disease were identified between 1999 and 2015. Incidence increased with age and at all ages was greater in men than women. In women and men, respectively, crude incidence increased from 0.037 and 0.074/10 000 population per year among those 45–49 years of age to 3.7 and 6.3/10 000 population per year among those ≥85 years. The overall standardized incidence decreased from 0.75/10 000 person-years in 1999 to 0.20/10 000 person-years in 2015. After adjustment for age and sex, incidence was >30% higher in the most- compared with least-deprived quintile of deprivation. There was evidence of geographic variation, with the highest incidence in the North West of England, which persisted after adjustment for age, sex and level of deprivation.

Conclusion

The incidence of clinically diagnosed Paget’s disease has continued to decrease since 1999. The reason for the decline in incidence remains unknown, although the rapidity of change points to an alteration in one or more environmental determinants.
A review and roadmap of the skin, lung and gut microbiota in systemic sclerosis
Authors: Teaw Shannon , Hinchcliff Monique , Cheng Michelle
Published: March 2021

As our understanding of the genetic underpinnings of SSc increases, questions regarding the environmental trigger(s) that induce and propagate SSc in the genetically predisposed individual emerge. The interplay between the environment, the immune system, and the microbial species that inhabit the patient’s skin and gastrointestinal tract is a pathobiological frontier that is largely unexplored in SSc. The purpose of this review is to provide an overview of the methodologies, experimental study results and future roadmap for elucidating the relationship between the SSc host and his/her microbiome.
Distribution of anti-melanoma differentiation associated gene 5 (MDA5) IgG subclasses in MDA5+ dermatomyositis
Authors: Chen Mengya , Zhao Qian , Diao Licheng , Xue Ke , Ruan Yeping , Xue Feng , Li Jian , Shi Ruofei , Pan Meng , Zheng Jie , Cao Hua
Published: March 2021

Objectives

The anti-melanoma differentiation-associated gene 5 (MDA5) antibody is the main predictor of interstitial lung disease (ILD) in DM and clinically amyopathic DM (CADM). Nevertheless, a subset of MDA5+ patients have a favourable prognosis. We aimed to determine the possibility of using anti-MDA5 antibody isotypes and IgG subclasses for evaluating ILD risk.

Methods

The isotypes (IgG, IgA and IgM) of anti-MDA5 were detected in serum samples of 36 anti-MDA5+ patients with DM/CADM using ELISA. IgG subclasses of anti-MDA5 antibodies were further investigated. Laboratory findings and cumulative survival were analysed based on the isotypes of anti-MDA5 and subclasses of anti-MDA5 IgG.

Results

Among the MDA5+ patients with DM/CADM, the positive rates of anti-MDA5 IgG, IgA and IgM were 100, 97 and 6%, respectively. The positive rates of anti-MDA5 IgG1, IgG2, IgG3 and IgG4 were 72, 25, 0 and 28%, respectively. The incidence of acute interstitial pneumonia, mortality rate and serum ferritin were significantly higher in anti-MDA5 IgG1+ patients than in anti-MDA5 IgG1− patients with DM/CADM (P = 0.0027, 0.015, 0.0011, respectively). The sensitivity and specificity of anti-MDA5 IgG1 for predicting mortality were 100 and 41.7%, respectively. A combination of anti-MDA5 IgG1 and IgG4 for predicting mortality yielded better specificity (87.5%).

Conclusion

IgA and IgG are the primary anti-MDA5 antibody isotypes. Anti-MDA5 IgG1 is the primary component of MDA5 IgG subclasses and anti-MDA5 IgG1 and IgG4 might serve as useful biomarkers for predicting mortality in DM-ILD.
Epidemiology of biopsy-confirmed giant cell arteritis in southern Sweden—an update on incidence and first prevalence estimate
Authors: Stamatis Pavlos , Turkiewicz Aleksandra , Englund Martin , Turesson Carl , Mohammad Aladdin J
Published: March 2021

Objective

To characterize the epidemiology of temporal artery biopsy-positive (TAB+) GCA, including trends in incidence, seasonal variation and prevalence in Skåne, the southernmost region of Sweden.

Methods

All histopathology reports of TABs from 1997 through 2019 were reviewed to identify patients diagnosed with TAB+ GCA. Incidence rates based on the 23-year period and the point-prevalence at 31 December 2014 were determined. An alternative prevalence calculation included only TAB+ GCA patients living in the study area and receiving immunosuppressant therapy on the point-prevalence date.

Results

One thousand three hundred and sixty patients were diagnosed with TAB+ GCA (71% female). The average annual incidence 1997–2019 was 13.3 (95% CI: 12.6, 14.0) per 100 000 inhabitants aged ≥50 years and was higher in females (17.8; 95% CI: 16.7, 18.9) than in males (8.2; 95% CI: 7.4, 9.0). The age- and sex-standardized incidence declined from 17.3 in 1997 to 8.7 in 2019, with incidence ratio (IR) of 0.98 per year (95% CI: 0.98, 0.99). A seasonal variation was observed with higher incidence during spring than winter [IR = 1.19 (95% CI: 1.03, 1.39)]. The overall point-prevalence of TAB+ GCA was 127.1/100 000 (95% CI: 117, 137.3) and was 75.5 (95% CI: 67.7, 83.3) when including only patients receiving immunosuppressants.

Conclusion

Over the past 2 decades, the incidence of biopsy-confirmed GCA has decreased by ∼2% per year. Still, a high prevalence of GCA on current treatment was observed. More cases are diagnosed during spring and summer than in the winter.
Myocardial involvement characteristics by cardiac MR imaging in patients with polymyositis and dermatomyositis
Authors: Feng Changjing , Liu Wangyan , Sun Xiaoxuan , Wang Qiang , Zhu Xiaomei , Zhou Xiaoyue , Xu Yi , Zhu Yinsu
Published: March 2021

Objective

Myocardial involvement is frequently observed in PM and DM but typically remains subclinical. This study aimed to investigate characteristics of myocardial involvement and compare differences between patients with PM and DM by cardiac MR (CMR) imaging.

Methods

From March 2017 to December 2019, a total of 17 PM and 27 DM patients were enrolled in this retrospective study. In all patients, clinical assessment and CMR examination were performed. CMR parameters, including left ventricular (LV) morphologic and functional parameters, and CMR tissue characterization imaging parameters, such as native T1, T2, extracellular volume (ECV) and late gadolinium enhancement, were analysed.

Results

In patients in both PM and DM groups, elevated global native T1 and ECV values were observed. Global ECV values were higher in the PM group when compared with the DM group (33.24 ± 2.97% vs 30.36 ± 4.20%; P = 0.039). Furthermore, patients in the PM and DM groups showed a different positive segment distribution of late gadolinium enhancement, native T1 and ECV, whereas the number of positive segments in PM patients was greater compared with that in DM patients. No significant differences in LV morphological and functional parameters were observed between patients in PM and DM groups, and most were in normal range.

Conclusion

CMR tissue characterization imaging could detect early myocardial involvement in PM and DM patients without overt LV dysfunction. Furthermore, characteristics of myocardial involvement were different between PM and DM patients with more serious myocardial involvement seen in PM patients.
Doppler ultrasound predicts successful discontinuation of biological DMARDs in rheumatoid arthritis patients in clinical remission
Authors: Terslev Lene , Brahe Cecilie Heegaard , Hetland Merete Lund , Georgiadis Stylianos , Ellegaard Karen , Juul Lars , Huynh Tuan , Døhn Uffe Møller , Fana Viktoria , Møller Torsten  , Krabbe Simon , Ørnbjerg Lykke Midtbøll , Glinatsi Daniel , Røgind Henrik , Hansen Anette , Nørregaard Jesper , Jacobsen Søren , Jensen Dorte Vendelbo , Manilo Natalia  , Asmussen Karsten , Boesen Mikael , Rastiemadabadi Zoreh , Morsel-Carlsen Lone  , Møller Jakob Møllenbach , Krogh Niels Steen , Østergaard Mikkel 
Published: March 2021

Objective

To assess the ability of ultrasound to predict successful tapering and successful discontinuation of biological DMARDs (bDMARDs) at the 2-year follow-up in RA patients in sustained remission.

Methods

Patients in sustained remission (DAS28-CRP ≤ 2.6) and with no radiographic progression the previous year tapered bDMARDs according to a standardized regime. A total of 119 of these patients were included in this ultrasound substudy. At baseline, clinical assessment, MRI, X-ray and ultrasound of 24 joints were performed. Ultrasound-detected synovitis was defined and scored 0–3 using the OMERACT scoring system at the joint level for both grey-scale and Doppler activity. Sum scores for each ultrasound modality were calculated for 24 joints at the patient level. The final state of treatment was assessed after 2 years. The predictive value of ultrasound measures for successful tapering and discontinuation at the 2-year follow-up was assessed via logistic regression analyses.

Results

Negative IgM-RF [odds ratio (OR) = 0.29, 95% CI: 0.10–0.85; P = 0.024] and lower Doppler sum score of 24 joints (OR = 0.44, 95% CI: 0.15, 0.87; P = 0.014) were independent predictors for successful discontinuation of bDMARDs at the 2-year follow-up. The predictive value of the Doppler sum score was independent of MRI findings. Previous numbers of bDMARDs were predictive of successful tapering (OR = 0.58, 95% CI: 0.35, 0.91; P = 0.018), whereas ultrasound was not. Clinical parameters were not predictive of successful tapering/discontinuation.

Conclusion

Doppler sum score was an independent predictor for successful discontinuation of bDMARDs at the 2-year follow-up—the odds for achieving successful discontinuation decreased by 56% per one-unit increase in Doppler sum score. Ultrasound could not predict successful tapering.
Growth differentiation factor 15 (GDF-15) as potential cardiovascular risk biomarker in antiphospholipid syndrome
Authors: Tektonidou Maria G , Papassotiriou Ioannis , Sfikakis Petros P
Published: March 2021

Objective

An interplay between thrombo-inflammatory and atherogenic mechanisms is recognized in cardiovascular disease (CVD) pathogenesis in APS. Herein, we examine associations of growth differentiation factor-15 (GDF-15), a pro-inflammatory cytokine identified as a potent CVD risk biomarker in the general population, with subclinical atherosclerosis in APS.

Methods

We measured plasma GDF-15 levels by an electrochemiluminescence immunoassay (cut-off 1200 pg/ml) and we examined carotid intima-media thickness (IMT) and the presence of carotid and femoral plaques using vascular ultrasound in 80 patients with APS (44 primary, 36 SLE/APS) and 40 healthy controls. We calculated the adjusted Global APS Score for cardiovascular disease (aGAPSSCVD), a revised adjusted Global APS Score (aGAPSS) for predicting CVD, including lupus anticoagulant, anticardiolipin and anti-beta2glycoprotein-I antibodies, and hypertension, dyslipidaemia, obesity, diabetes and smoking.

Results

GDF-15 levels were higher in APS patients vs controls, after adjusting for age and gender [absolute difference: 281 (95% CI: 141, 421) pg/ml, P < 0.001]. GDF-15 levels ≥1200 pg/ml were associated with higher mean IMT of the right and left carotid arteries [beta coefficient 0.068 (95% CI: 0.020, 0.116), P = 0.006] compared with GDF-15 levels <1200 pg/ml. GDF-15 was independently associated with mean IMT, after adjusting for gender and aGAPSSCVD [beta coefficient 0.059 (95% CI: 0.008, 0.110), P = 0.024], and additionally for statin (P = 0.025) and HCQ use (P = 0.011). GDF-15 levels ≥1200 pg/ml were associated with 2.4 times higher odds for atherosclerotic plaques (odds ratios = 2.438, 95% CI: 0.906, 6.556, P = 0.078), while this effect was reduced by including more covariates in the model.

Conclusion

GDF-15 is independently associated with subclinical atherosclerosis in APS patients, suggesting its potential role in CVD risk stratification in APS.
Anti-RNPC-3 antibody predicts poor prognosis in patients with interstitial lung disease associated to systemic sclerosis
Authors: Callejas-Moraga Eduardo Luis , Guillén-Del-Castillo Alfredo , Perurena-Prieto Janire , Sanz-Martínez Maria Teresa , Fonollosa-Pla Vicente , Lorite-Gomez Karen , Severino Adriana , Bellocchi Chiara , Beretta Lorenzo , Mahler Michael , Simeón-Aznar Carmen P
Published: March 2021

Objective

To analyse the prevalence, the clinical characteristics, the overall survival and the event-free survival (EFS) of SSc patients who express anti-U11/U12 RNP (RNPC-3) antibodies.

Methods

A total of 447 SSc patients from Barcelona (n = 286) and Milan (n = 161) were selected. All samples were tested using a particle-based multi-analyte technology. We compared anti-RNPC-3 positive and negative patients. Epidemiological, clinical features and survival were analysed. End-stage lung disease (ESLD) was defined if the patient developed forced vital capacity <50% of predicted, needed oxygen therapy or lung transplantation. EFS was defined as the period of time free of either ESLD or death.

Results

Nineteen of 447 (4.3%) patients had anti-RNPC-3 antibodies and interstitial lung disease (ILD) was more frequent (11, 57.9% vs 144, 33.6%, P =0.030) in individuals with anti-RNPC-3 antibodies. More patients reached ESLD in the positive group (7, 36.8% vs 74, 17.3%, P = 0.006), and a higher use of non-glucocorticoid immunosuppressive drugs was observed (11, 57.9% vs 130, 30.4%, P = 0.012). Anti-RNPC-3 positive patients had lower EFS, both in the total cohort (log-rank P =0.001), as well as in patients with ILD (log-rank P = 0.002). In multivariate Cox regression analysis, diffuse cutaneous subtype, age at onset, the presence of ILD or pulmonary arterial hypertension and the expression of anti-RNPC-3 positivity or anti-topo I were independently associated with worse EFS.

Conclusion

The presence of anti-RNPC-3 was associated with higher frequency of ILD and either ESLD or death. These data suggest anti-RNPC-3 is an independent poor prognosis antibody in SSc, especially if ILD is also present.
Psychopathological Syndromes Across Affective and Psychotic Disorders Correlate With Gray Matter Volumes
Authors: Stein Frederike , Meller Tina , Brosch Katharina , Schmitt Simon , Ringwald Kai , Pfarr Julia Katharina , Meinert Susanne , Thiel Katharina , Lemke Hannah , Waltemate Lena , Grotegerd Dominik , Opel Nils , Jansen Andreas , Nenadić Igor , Dannlowski Udo , Krug Axel , Kircher Tilo
Published: March 2021

Introduction

More than a century of research on the neurobiological underpinnings of major psychiatric disorders (major depressive disorder [MDD], bipolar disorder [BD], schizophrenia [SZ], and schizoaffective disorder [SZA]) has been unable to identify diagnostic markers. An alternative approach is to study dimensional psychopathological syndromes that cut across categorical diagnoses. The aim of the current study was to identify gray matter volume (GMV) correlates of transdiagnostic symptom dimensions.

Methods

We tested the association of 5 psychopathological factors with GMV using multiple regression models in a sample of N = 1069 patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for MDD (n = 818), BD (n = 132), and SZ/SZA (n = 119). T1-weighted brain images were acquired with 3-Tesla magnetic resonance imaging and preprocessed with CAT12. Interactions analyses (diagnosis × psychopathological factor) were performed to test whether local GMV associations were driven by DSM-IV diagnosis. We further tested syndrome specific regions of interest (ROIs).

Results

Whole brain analysis showed a significant negative association of the positive formal thought disorder factor with GMV in the right middle frontal gyrus, the paranoid-hallucinatory syndrome in the right fusiform, and the left middle frontal gyri. ROI analyses further showed additional negative associations, including the negative syndrome with bilateral frontal opercula, positive formal thought disorder with the left amygdala-hippocampus complex, and the paranoid-hallucinatory syndrome with the left angular gyrus. None of the GMV associations interacted with DSM-IV diagnosis.

Conclusions

We found associations between psychopathological syndromes and regional GMV independent of diagnosis. Our findings open a new avenue for neurobiological research across disorders, using syndrome-based approaches rather than categorical diagnoses.
Does Perceived Loneliness Matter for Diverse Older Men and Their Prostate-Specific Antigen Testing Behaviors?
Authors: Cadet Tamara , Burke Shanna Lynn , Mitchell Jamie , Conner Kyaien O. , Nedjat-Haiem Frances
Published: March 2021

Loneliness is associated with poorer health practices and fewer health-promoting behaviors and may be associated with greater use of the health care system. Given national conversations about aging in context, this investigation explored the relationship between perceptions of loneliness in 2008 and prostate cancer screening participation in 2008 and 2012. Using data from the Health and Retirement Study, authors examined the relationship between loneliness and prostate cancer screening in 2008 and 2012 among Black, Hispanic, and non-Hispanic White men, ages 50 to 74 years (N = 4,875) using a series of logistic regression models. Findings indicate that White men who indicated being more lonely were less likely to participate in screening in 2008 and 2012. For Black men, there was a reduced likelihood of screening in 2012 with one aspect of decreasing loneliness. Social workers have unique training focusing on the person-in-environment model. Use of the person-in-environment model can help health care providers understand men’s experiences and their feelings or needs related to cancer screening participation. Given the lack of focus on men’s health-promoting behaviors related to loneliness, this study provides formative data to test interventions to increase the well-being of older men.
“I’ve Been Through It”: Assessing Employment Barriers among Unaccompanied Women Experiencing Homelessness
Authors: Groton Danielle , Radey Melissa
Published: March 2021

Women represent a growing segment of the homeless population; however, little work has examined employment among an important segment of this population: women unaccompanied by children. This study addressed the following research questions: Which common employment barriers (that is, physical health, mental health, substance abuse, or domestic violence) influence employment of unaccompanied women experiencing homelessness? How do these barriers influence the employment experiences of the women? The authors analyzed a cross-sectional sample of unaccompanied women in one community’s homeless management information system (n = 1,331). Then they completed semistructured interviews (n = 20) with a subsample of these women. Logistic regression analyses indicated that no employment barrier significantly related to current employment status. Interview data indicated that women perceived physical and mental health issues as barriers to full-time employment. Women reported a struggle to maintain housing even when they had employment. Integrated quantitative and qualitative analyses identified how agency data regarding barriers and employment may miss central barriers (for example, stigma, physical presentation) and employment engagement. Study findings provide support for programs that address housing and current barriers before other employment barriers, the importance of improving federal measures, and recommendations to strengthen agency-level data collection to inform program development and community-based research.
Social Work Burnout in the Context of Interprofessional Collaboration
Authors: McCarthy Lauren Pryce
Published: March 2021

This study builds on the existing research in the field of interprofessional collaboration (IPC) and burnout among social workers. The authors sampled field instructors from a mid-Atlantic school of social work, comparing self-reported burnout scores among social workers on interprofessional teams with those of social workers who do not work on interprofessional teams, and completed a regression analysis of the relationship between burnout and participation in interprofessional teams, perceptions of IPC, and several individual and practice factors. Findings suggest that although members of interprofessional teams reported lower burnout scores, there was no significant relationship between working in an interprofessional team and burnout when controlling for other factors. Although the study provides an interesting first look at burnout among social workers in interprofessional teams, further research with a larger, more representative sample is needed.
Costs of TB care incurred by adult patients with newly diagnosed drug-sensitive TB in Ballabgarh block in northern India
Authors: Chandra Ankit , Kumar Rakesh , Kant Shashi , Krishnan Anand
Published: March 2021

Background

India's National Tuberculosis Elimination Programme (NTEP) provides free diagnosis and treatment services but does not monitor TB-related costs. This study aimed to estimate the direct and indirect costs borne by adult patients with newly diagnosed TB.

Methods

A longitudinal study in Ballabgarh block, Haryana (North India) was conducted. A total of 110 patients were interviewed and data regarding costs were collected at three points of time (after diagnosis, at the end of intensive phase and at the end of the treatment) using a semistructured questionnaire. The total direct (out-of-pocket expenses) and indirect (income lost) costs before and during treatment were calculated for patients who completed the treatment.

Results

We enrolled 110 patients with drug-sensitive TB; 6 patients could not complete the treatment. The TB-related median total cost was US$150 (IQR 65–335). The median prediagnosis and postdiagnosis costs were US$42 (IQR 19–313) and US$63 (IQR 10.2–190), respectively. The median direct and indirect costs were US$75 (IQR 36–148) and US$16 (IQR 0–197), respectively. A catastrophic cost was experienced by 18% (95% CI 12 to 27%) of households.

Conclusion

Despite free diagnosis and treatment services, there is a substantial TB-related cost for TB care under the NTEP. Accelerated efforts are needed to achieve the target of zero catastrophic cost.
Huanglongbing and Citrus Variegated Chlorosis Integrated Management Based on Favorable Periods for Vector Population Increase and Symptom Expression
Authors: Bassanezi Renato Beozzo , Primiano Isabela Vescove
Published: March 2021

Huanglongbing (HLB, associated with Candidatus Liberibacter asiaticus and transmitted by the Asian citrus psyllid Diaphorina citri) and citrus variegated chlorosis (CVC, caused by Xylella fastidiosa subsp. pauca and transmitted by sharpshooter species) have been managed by vector control and removal of symptomatic trees. Although vectors and new symptomatic trees can be detected year round, peaks of vector populations are higher in spring and summer, and the most symptomatic trees are found in autumn and winter. This work aimed to compare the management of both diseases during these favorable periods. The experiment was conducted during 5 years in a commercial orchard and had a three-by-two factorial design. The factor “vector control” had three levels: monthly vector control year round (VCYR), monthly vector control in spring and summer (VCSS), and vector control when a threshold level of 10% occupancy was detected (VCOT). The factor “inoculum removal” had two levels: monthly eradication year round (TEYR) and monthly eradication in autumn and winter (TEAW). Host flush, both HLB and CVC vector populations, and the number of symptomatic citrus plants were visually assessed. The level of vectors over the seasons, as measured using the average area under the curve (AUC), was similar for all treatments with the exception of psyllid abundance, which was approximately 4.5 times higher for VCSS than for other treatments. For both diseases, no difference in the average AUC of disease progress and disease final incidence was observed. VCOT or adjusted VCSS associated with TEAW could be integrated for sustainable citrus production.
Quantitative Trait Locus Mapping for Common Scab Resistance in a Tetraploid Potato Full-Sib Population
Authors: da Silva Pereira Guilherme , Mollinari Marcelo , Qu Xinshun , Thill Christian , Zeng Zhao-Bang , Haynes Kathleen , Yencho G. Craig
Published: March 2021

Despite the negative impact of common scab (Streptomyces spp.) on the potato industry, little is known about the genetic architecture of resistance to this bacterial disease in the crop. We evaluated a mapping population (∼150 full sibs) derived from a cross between two tetraploid potatoes (‘Atlantic’ × B1829-5) in three environments (MN11, PA11, ME12) under natural common scab pressure. Three measures to common scab reaction, namely percentage of scabby tubers and disease area and lesion indices, were found to be highly correlated (>0.76). Because of the large environmental effect, heritability values were zero for all three traits in MN11, but moderate to high in PA11 and ME12 (∼0.44 to 0.79). We identified a single quantitative trait locus (QTL) for lesion index in PA11, ME12, and joint analyses on linkage group 3, explaining ∼22 to 30% of the total variation. The identification of QTL haplotypes and candidate genes contributing to disease resistance can support genomics-assisted breeding approaches in the crop.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Demographics of Surgical Specialty Residency Program Directors in the United States: A Cross-sectional Analysis
Authors: Patel Annika , Burton Adam , Pandya Shivani , Venincasa Michael , Gedde Steven J. , Cavuoto Kara M. , Sridhar Divya , Kloosterboer Amy , Sridhar Jayanth
Published: March 2021

Objective:

To evaluate program director (PD) demographics, training background, and academic productivity in 11 surgical specialties.

Summary Background Data:

There is currently no comprehensive study comparing educational background, research output, and gender differences between PDs of surgical residencies in the United States.

Methods:

The Accreditation Council for Graduate Medical Education (ACGME) and the Association of American Medical Colleges (AAMC) websites were used to identify residency PDs. Age, information related to service as PD, educational background, and research output were collected utilizing online searches including Doximity, PubMed, and Scopus. The ACGME Data Resource Book was used to obtain data on the gender makeup of residents in each surgical specialty. Data collection occurred between December 14, 2019, and May 9, 2020.

Results:

One thousand five hundred seventy-one residency PDs across 11 surgical specialties were included. Significant differences between specialties were found with respect to PD gender, current age, age at appointment, years between residency and assignment, term duration, number of PubMed publications, and Scopus h-index. The current age (mean ± SD) ranged from 46.8 ± 8.5 years among Interventional Radiology (IR) PDs to 53.4 ± 9.1 years among Neurological Surgery (NEUROSURG) PDs. The proportion of female PDs ranged from 5.9% in NEUROSURG to 63.5% in Obstetrics and Gynecology (OB-GYN). Completion of a postresidency fellowship was least common for OB-GYN PDs at 9.1% and most common for IR PDs at 98.8%. The number (mean ± SD) of PubMed publications and Scopus h-index ranged from 13.1 ± 22.3 publications and h index 4.5 ± 5.7 among OB-GYN PDs to 112.5 ± 103.0 publications and h index 27.4 ± 16.7 among Thoracic Surgery PDs. Age and academic productivity as measured by PubMed publications and Scopus h-index were significantly lower among female PDs in multiple surgical specialties.

Conclusions:

There were significant variations in the PDs of surgical specialties, particularly with respect to gender and academic productivity. Efforts should be made to support and encourage greater female representation in the role of surgical residency PD.
Decreased Intestinal Microbiome Diversity in Pediatric Sepsis: A Conceptual Framework for Intestinal Dysbiosis to Influence Immunometabolic Function
Authors: Weiss Scott L. , Bittinger Kyle , Lee Jung-Jin , Friedman Elliot S. , Mattei Lisa M. , Graham Kathryn , Zhang Donglan , Bush Jeny , Balamuth Fran , McGowan Francis X. , Bushman Frederic D. , Baldassano Robert N. , Wu Gary D. , Wallace Douglas C. , Collman Ronald G.
Published: March 2021

Objectives:

The intestinal microbiome can modulate immune function through production of microbial-derived short-chain fatty acids. We explored whether intestinal dysbiosis in children with sepsis leads to changes in microbial-derived short-chain fatty acids in plasma and stool that are associated with immunometabolic dysfunction in peripheral blood mononuclear cells.

Design:

Prospective observational pilot study.

Setting:

Single academic PICU.

Patients:

Forty-three children with sepsis/septic shock and 44 healthy controls.

Measurements and Main Results:

Stool and plasma samples were serially collected for sepsis patients; stool was collected once for controls. The intestinal microbiome was assessed using 16S ribosomal RNA sequencing and alpha- and beta-diversity were determined. We measured short-chain fatty acids using liquid chromatography, peripheral blood mononuclear cell mitochondrial respiration using high-resolution respirometry, and immune function using ex vivo lipopolysaccharide-stimulated whole blood tumor necrosis factor-α. Sepsis patients exhibited reduced microbial diversity compared with healthy controls, with lower alpha- and beta-diversity. Reduced microbial diversity among sepsis patients (mainly from lower abundance of commensal obligate anaerobes) was associated with increased acetic and propionic acid and decreased butyric, isobutyric, and caproic acid. Decreased levels of plasma butyric acid were further associated with lower peripheral blood mononuclear cell mitochondrial respiration, which in turn, was associated with lower lipopolysaccharide-stimulated tumor necrosis factor-α. However, neither intestinal dysbiosis nor specific patterns of short-chain fatty acids were associated with lipopolysaccharide-stimulated tumor necrosis factor-α.

Conclusions:

Intestinal dysbiosis was associated with altered short-chain fatty acid metabolites in children with sepsis, but these findings were not linked directly to mitochondrial or immunologic changes. More detailed mechanistic studies are needed to test the role of microbial-derived short-chain fatty acids in the progression of sepsis.
Preclinical models of endometriosis and interstitial cystitis/bladder pain syndrome: an Innovative Medicines Initiative-PainCare initiative to improve their value for translational research in pelvic pain
Authors: Nunez-Badinez Paulina , De Leo Bianca , Laux-Biehlmann Alexis , Hoffmann Anja , Zollner Thomas M. , Saunders Philippa T.K. , Simitsidellis Ioannis , Charrua Ana , Cruz Francisco , Gomez Raul , Tejada Miguel Angel , McMahon Stephen B. , Lo Re Laure , Barthas Florent , Vincent Katy , Birch Judy , Meijlink Jane , Hummelshoj Lone , Sweeney Patrick J. , Armstrong J. Douglas , Treede Rolf-Detlef , Nagel Jens
Published: March 2021

Endometriosis (ENDO) and interstitial cystitis/bladder pain syndrome (IC/BPS) are chronic pain conditions for which better treatments are urgently needed. Development of new therapies with proven clinical benefit has been slow. We have conducted a review of existing preclinical in vivo models for ENDO and IC/BPS in rodents, discussed to what extent they replicate the phenotype and pain experience of patients, as well as their relevance for translational research. In 1009 publications detailing ENDO models, 41% used autologous, 26% syngeneic, 18% xenograft, and 11% allogeneic tissue in transplantation models. Intraperitoneal injection of endometrial tissue was the subcategory with the highest construct validity score for translational research. From 1055 IC/BPS publications, most interventions were bladder centric (85%), followed by complex mechanisms (8%) and stress-induced models (7%). Within these categories, the most frequently used models were instillation of irritants (92%), autoimmune (43%), and water avoidance stress (39%), respectively. Notably, although pelvic pain is a hallmark of both conditions and a key endpoint for development of novel therapies, only a small proportion of the studies (models of ENDO: 0.5%-12% and models of IC/BPS: 20%-44%) examined endpoints associated with pain. Moreover, only 2% and 3% of publications using models of ENDO and IC/BPS investigated nonevoked pain endpoints. This analysis highlights the wide variety of models used, limiting reproducibility and translation of results. We recommend refining models so that they better reflect clinical reality, sharing protocols, and using standardized endpoints to improve reproducibility. We are addressing this in our project Innovative Medicines Initiative-PainCare/Translational Research in Pelvic Pain.
Barriers and facilitators to older adults' use of nonpharmacologic approaches for chronic pain: a person-focused model
Authors: Garrett Sarah B. , Nicosia Francesca , Thompson Nicole , Miaskowski Christine , Ritchie Christine S.
Published: March 2021

In the context of the opioid epidemic and the growing population of older adults living with chronic pain, clinicians are increasingly recommending nonpharmacologic approaches to patients as complements to or substitutes for pharmacologic treatments for pain. Currently, little is known about the factors that influence older adults' use of these approaches. We aimed to characterize the factors that hinder or support the use of nonpharmacologic approaches for pain management among older adults with multiple morbidities. We collected semistructured qualitative interview data from 25 older adults with multiple morbidities living with chronic pain for 6 months or more. Transcripts were coded to identify factors that hindered or supported participants' use of various nonpharmacologic approaches. We used the constant comparative method to develop a person-focused model of barriers and facilitators to participants' use of these approaches for chronic pain management. Participants described a wide range of factors that influenced their use of nonpharmacologic approaches. We grouped these factors into 3 person-focused domains: awareness of the nonpharmacologic approach as relevant to their chronic pain, appeal of the approach, and access to the approach. We propose and illustrate a conceptual model of barriers and facilitators to guide research and clinical care. This study identifies numerous factors that influence patients' use of nonpharmacologic approaches, some of which are not captured in existing research or routinely addressed in clinical practice. The person-centered model proposed may help to structure and support patient–clinician communication about nonpharmacologic approaches to chronic pain management.