bluuebunny/crossref_metadata_2025 huggingface dataset:
The ‘un-shrunk’ partial correlation in Gaussian graphical models
Authors: Bernal Victor , Bischoff Rainer , Horvatovich Peter , Guryev Victor , Grzegorczyk Marco
Published: September 2021

Background

In systems biology, it is important to reconstruct regulatory networks from quantitative molecular profiles. Gaussian graphical models (GGMs) are one of the most popular methods to this end. A GGM consists of nodes (representing the transcripts, metabolites or proteins) inter-connected by edges (reflecting their partial correlations). Learning the edges from quantitative molecular profiles is statistically challenging, as there are usually fewer samples than nodes (‘high dimensional problem’). Shrinkage methods address this issue by learning a regularized GGM. However, it remains open to study how the shrinkage affects the final result and its interpretation.

Results

We show that the shrinkage biases the partial correlation in a non-linear way. This bias does not only change the magnitudes of the partial correlations but also affects their order. Furthermore, it makes networks obtained from different experiments incomparable and hinders their biological interpretation. We propose a method, referred to as ‘un-shrinking’ the partial correlation, which corrects for this non-linear bias. Unlike traditional methods, which use a fixed shrinkage value, the new approach provides partial correlations that are closer to the actual (population) values and that are easier to interpret. This is demonstrated on two gene expression datasets from Escherichia coli and Mus musculus.

Conclusions

GGMs are popular undirected graphical models based on partial correlations. The application of GGMs to reconstruct regulatory networks is commonly performed using shrinkage to overcome the ‘high-dimensional problem’. Besides it advantages, we have identified that the shrinkage introduces a non-linear bias in the partial correlations. Ignoring this type of effects caused by the shrinkage can obscure the interpretation of the network, and impede the validation of earlier reported results.
SNPxE: SNP-environment interaction pattern identifier
Authors: Lin Hui-Yi , Huang Po-Yu , Tseng Tung-Sung , Park Jong Y.
Published: September 2021

Background

Interactions of single nucleotide polymorphisms (SNPs) and environmental factors play an important role in understanding complex diseases' pathogenesis. A growing number of SNP-environment studies have been conducted in the past decade; however, the statistical methods for evaluating SNP-environment interactions are still underdeveloped. The conventional statistical approach with a full interaction model with an additive SNP mode tests one specific interaction type, so the full interaction model approach tends to lead to false-negative findings. To increase detection accuracy, developing a statistical tool to effectively detect various SNP-environment interaction patterns is necessary.

Results

SNPxE, a SNP-environment interaction pattern identifier, tests multiple interaction patterns associated with a phenotype for each SNP-environment pair. SNPxE evaluates 27 interaction patterns for an ordinal environment factor and 18 patterns for a categorical environment factor. For detecting SNP-environment interactions, SNPxE considers three major components: (1) model structure, (2) SNP’s inheritance mode, and (3) risk direction. Among the multiple testing patterns, the best interaction pattern will be identified based on the Bayesian information criterion or the smallest p-value of the interaction. Furthermore, the risk sub-groups based on the SNPs and environmental factors can be identified. SNPxE can be applied to both numeric and binary phenotypes. For better results interpretation, a heat-table of the outcome proportions can be generated for the sub-groups of a SNP-environment pair.

Conclusions

SNPxE is a valuable tool for intensively evaluate SNP-environment interactions, and the SNPxE findings can provide insights for solving the missing heritability issue. The R function of SNPxE is freely available for download at GitHub (https://github.com/LinHuiyi/SIPI).
LncRNA TCONS_00021861 is functionally associated with drought tolerance in rice (Oryza sativa L.) via competing endogenous RNA regulation
Authors: Chen Jiajia , Zhong Yuqing , Qi Xin
Published: September 2021

Background

Water deficit is an abiotic stress that retards plant growth and destabilizes crop production. Long non coding RNAs (lncRNAs) are a class of non-coding endogenous RNAs that participate in diverse cellular processes and stress responses in plants. lncRNAs could function as competing endogenous RNAs (ceRNA) and represent a novel layer of gene regulation. However, the regulatory mechanism of lncRNAs as ceRNA in drought stress response is yet unclear.

Results

In this study, we performed transcriptome-wide identification of drought-responsive lncRNAs in rice. Thereafter, we constructed a lncRNA-mediated ceRNA network by analyzing competing relationships between mRNAs and lncRNAs based on ceRNA hypothesis. A drought responsive ceRNA network with 40 lncRNAs, 23 miRNAs and 103 mRNAs was obtained. Network analysis revealed TCONS_00021861/miR528-3p/YUCCA7 regulatory axis as a hub involved in drought response. The miRNA-target expression and interaction were validated by RT-qPCR and RLM-5’RACE. TCONS_00021861 showed significant positive correlation (r = 0.7102) with YUCCA7 and negative correlation with miR528-3p (r = -0.7483). Overexpression of TCONS_00021861 attenuated the repression of miR528-3p on YUCCA7, leading to increased IAA (Indole-3-acetic acid) content and auxin overproduction phenotypes.

Conclusions

TCONS_00021861 could regulate YUCCA7 by sponging miR528-3p, which in turn activates IAA biosynthetic pathway and confer resistance to drought stress. Our findings provide a new perspective of the regulatory roles of lncRNAs as ceRNAs in drought resistance of rice.
Accuracy of neutrophil to lymphocyte and monocyte to lymphocyte ratios as new inflammatory markers in acute coronary syndrome
Authors: Shumilah Ahmed Mohammed , Othman Arwa Mohammed , Al-Madhagi Anwar Kasim
Published: September 2021

Background

Inflammation plays a key role in the development of atherosclerosis and in the pathogenesis of acute coronary syndrome (ACS). Leukocytes and leukocytes ratios were recognized as inflammatory markers in predicting the presence and severity of ACS.

Methods

This study aimed to investigate the diagnostic accuracy of neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) with ACS. One hundred patients admitted to the Cardiac Center who were confirmed to have ACS and 100 healthy controls confirmed not to have ACS were enrolled in this study. ECG and troponin I test were used as gold standards to make sure that the participants with or without ACS. Total white blood cells (WBCs) count, NLR, and MLR values were estimated.

Results

Total WBCs, neutrophil, and monocyte counts were significantly higher while lymphocyte counts were significantly lower in ACS patients than in the healthy controls (p < 0.001). NLR and MLR were significantly higher in ACS patients than in the healthy controls (p < 0.001). Among all the studied markers, NLR was found to be the strongest predictive marker of ACS (OR: 3.3, p < 0.001), whereas MLR was non-significant (p > 0.05). A cut-off value of 2.9 of NLR had 90% sensitivity and 88% specificity while 0.375 cut-off value of MLR had 79% sensitivity, 91% specificity for predicting ACS presence.

Conclusions

NLR is a simple, widely available, and inexpensive inflammatory marker which can be an auxiliary biomarker in the diagnosis of ACS with a cut-off value of 2.9 in our population.
Experiences of renal healthcare practitioners during the COVID-19 pandemic: a multi-methods approach
Authors: Mc Keaveney Clare , Reid Joanne , Carswell Claire , Bonner Ann , de Barbieri Ilaria , Johnston William , Maxwell Alexander P. , O’Riordan Julien , Strini Veronica , Walsh Ian , Noble Helen
Published: September 2021

Background

Globally, renal healthcare practitioners provide intensive and protracted support to a highly complex multi-morbid patient population however knowledge about the impact of COVID-19 on these practitioners is extremely limited.

Objective

This study aimed to explore the experiences of COVID-19 with renal healthcare practitioners during the first global lockdown between June 2020 and September 2020.

Methods

A multi-methods approach was carried out including a quantitative survey and qualitative interviews. This was a multinational study of renal healthcare practitioners from 29 countries. Quantitative: A self-designed survey on COVID-19 experiences and standardised questionnaires (General Health Questionnaire-12; Maslach Burnout Inventory). Descriptive statistics were generated for numerical data. Qualitative: Online semi-structured interviews were conducted. Data was subjected to thematic analysis. Renal healthcare practitioners (n = 251) completed an online survey. Thirteen renal healthcare practitioners took part in semi-structured interviews (12 nurses and 1 dietician).

Results

The majority of participants surveyed were female (86.9 %; n = 218), nurses (86.9 %; n = 218) with an average 21.5 (SD = 11.1) years’ experience since professional qualification, and 16.3 years (SD = 9.3) working in renal healthcare. Survey responses indicated a level of preparedness, training and satisfactory personal protective equipment during the pandemic however approximately 40.3 % experienced fear about attending work, and 49.8 % experienced mental health distress. The highest prevalence of burnout was emotional exhaustion (35.9 %). Three themes emerged from the qualitative analysis highlighting the holistic complexities in managing renal healthcare, a neglected specialist workforce, and the need for appropriate support at work during a pandemic.

Conclusions

Results have highlighted the psychological impact, in terms of emotional exhaustion and mental health distress in our sample of renal healthcare practitioners. As the pandemic has continued, it is important to consider the long-term impact on an already stretched workforce including the risk of developing mental health disorders. Future research and interventions are required to understand and improve the provision of psychological support for specialist medical and nursing personnel.
Dysfunctional labor and hemoperitoneum secondary to an incidentally discovered dysgerminoma: a case report
Authors: Thannickal Aneesa , Maddy Brandon , DeWitt Marla , Cliby William , Dow Margaret
Published: September 2021

Background

Ovarian dysgerminoma, a subtype of malignant germ cell tumor (GCT), is a rare ovarian neoplasm that is infrequently found in the gravid patient. When dysgerminomas do occur in pregnancy, the rapidly growing tumors can have a heterogeneous presentation and lead to peripartum complications and morbidity. Due to the rarity of this condition, diagnostic and therapeutic strategies are not well described in the literature.

Case presentation

A healthy multigravida with an uncomplicated antenatal history presented for elective induction of labor. She had a protracted labor course, persistently abnormal cervical examinations, and eventually developed a worsening Category II tracing that prompted cesarean birth. Intraoperatively, a 26 cm pelvic mass later identified as a Stage IA dysgerminoma was discovered along with a massive hemoperitoneum. The mass was successfully resected, and the patient remains without recurrence 6 months postoperatively.

Conclusion

Although rare and generally indolent, dysgerminomas can grow rapidly and cause mechanical obstruction of labor and other complications in pregnancy. Pelvic masses, including malignant neoplasms, should be included in as part of a broad differential diagnosis when evaluating even routine intrapartum complications such as abnormal labor progression. Additionally, we demonstrate that adnexal masses can be a source of life-threatening intraabdominal hemorrhage.
Impact of childbirth policy changes on obstetric workload over a 13-year period in a regional referral center in China – implications on service provision planning
Authors: Xie Min , Lao Terence T , Ma Junnan , Zhu Tianying , Liu Dajin , Yu Shengnan , Du Mingyu , Sun Qian , Ma Runmei
Published: September 2021

Background

We aimed to appraise the impact of the changing national childbirth policy since 2002, currently allowing two children per family, on obstetric workload in a regional referral center in China.

Methods

In a retrospective cohort study, temporal changes were examined in relation with maternal demographics, incidence of women with high risk pregnancies and resource statistics in our hospital in managing singleton viable pregnancies (birth from 28 weeks gestational age onwards) for the period 2005–2017.

Results

During this 13-year period, the number of singleton livebirths from 28 weeks gestational age onwards was 49,479. Annual numbers of births increased from 1,941 to 2005 to 5,777 in 2017. There were concomitant and significant increases in the incidence of multiparous women (10.6–50.8 %), of age ≥35 years (6.5–24.3 %), with prior caesarean Sec. (2.6–23.6 %), with ≥3 previous pregnancy terminations (1.0–4.9 %), with pre-gestational diabetes (0.2–0.9 %), and with chronic hypertension (0.2–1.2 %). There were associated increases in beds and staff complement and reduced average hospital stay. Nevertheless, while the workload of medical staff remained stable with increasing staff complement, that of midwives increased significantly as reflected by the total births: midwife ratio which increased from 194.1:1 to 320.9:1 (p < 0.001).

Conclusions

In our hospital, progressively increasing numbers of annual births in combination with an increased incidence of women with high risk pregnancies took place following the revised national childbirth policy. Only the increase in medical and nursing, but not midwifery, staff was commensurate with workload. Remedial measures are urgently required before the anticipated progressive increase in care demand would overwhelm maternity care with potentially disastrous consequences.
CML derived exosomes promote tumor favorable functional performance in T cells
Authors: Jafarzadeh Nazli , Gholampour Mohammad Ali , Alivand Mohammad-Reza , Kavousi Saeideh , Arzi Laleh , Rad Fariba , Sadeghizadeh Majid , Pornour Majid
Published: September 2021

Background

Leukemic cells facilitate the creation of the tumor-favorable microenvironment in the bone marrow niche using their secreted factors. There are not comprehensive details about immunosuppressive properties of chronic myelogenous leukemia-derived exosomes in the bone marrow stromal and immune compartment. We explained here that K562-derived exosomes could affect the gene expression, cytokine secretion, nitric oxide (NO) production, and redox potential of human primary cord blood-derived T cells (CB T cells).

Methods

Human primary cord blood-derived T cells were treated with K562-derived exosomes. We evaluated the expression variation of some critical genes activated in suppressor T cells. The alterations of some inflammatory and anti-inflammatory cytokines levels were assessed using ELISA assay and real-time PCR. Finally, NO production and intracellular ROS level in CB T cells were evaluated using Greiss assay and flow cytometry, respectively.

Results

Our results showed the over-expression of the genes involved in inhibitory T cells, including NQO1, PD1, and FoxP3. In contrast, genes involved in T cell activation such as CD3d and NFATc3 have been reduced significantly. Also, the expression of interleukin 10 (IL-10) and interleukin 6 (IL-6) mRNAs were significantly up-regulated in these cells upon exosome treatment. In addition, secretion of the interleukin 10, interleukin 6, and interleukin 17 (IL-17) proteins increased in T cells exposed to K562-derived exosomes. Finally, K562-derived exosomes induce significant changes in the NO production and intracellular ROS levels in CB T cells.

Conclusions

These results demonstrate that K562-derived exosomes stimulate the immunosuppressive properties in CB-derived T cells by inducing anti-inflammatory cytokines such as IL-10, reducting ROS levels, and arising of NO synthesis in these cells. Moreover, considering the elevation of FOXP3, IL-6, and IL-17 levels in these cells, exosomes secreted by CML cells may induce the fates of T cells toward tumor favorable T cells instead of conventional activated T cells.
Association between student-teacher ratio and teachers’ working hours and workload stress: evidence from a nationwide survey in Japan
Authors: Hojo Masakazu
Published: September 2021

Background

Too long work hours of Japanese school teachers, along with an increasing number of teachers taking leave due to mental illness, are well known and recognized as a serious social problem. In order to prevent the spread of COVID-19 by reducing the density in the classroom, the Japanese government has decided to reduce the upper-limit of class size in primary schools after 2021, which is expected to result in lowering the student-teacher ratio. The aim of this study was to examine the association between student-teacher ratio, teacher work hours and teacher stress.

Methods

Data on student-teacher ratio, teacher work hours, and teacher stress were obtained from a large-scale international survey conducted by OECD. The number of teachers participated in the survey was 3308 (primary school) and 3555 (lower-secondary school). After excluding teachers with missing observations, the analytic sample consisted of 2761 (primary school) and 3006 (lower-secondary school) teachers. Multivariate regression analysis was performed.

Results

Regression results revealed that student-teacher ratio was positively correlated with total work hours and workload stress of teachers. In particular, teachers working in schools with high student-teacher ratio spent more time on time-consuming tasks such as marking/correcting student work and communication with parents or guardians. The coefficient estimates suggested that, on average, lowering the student-teacher ratio by five in lower-secondary school was associated with 2.8 hours shorter working hours per week (p<0.001).

Conclusion

Our empirical results suggested that the class-size reduction policy starting in 2021 could reduce teacher stress and long work hours through the consequent decrease in student-teacher ratios.
Postoperative controlling nutritional status score is an independent risk factor of survival for patients with small hepatocellular carcinoma: a retrospective study
Authors: Peng Wei , Yao Minghong , Zou Kang , Li Chuan , Wen Tianfu , Sun Xin
Published: September 2021

Background

The controlling nutritional status (CONUT) score has been widely used to evaluate the nutritional and immunological status. Clinical value of postoperative CONUT (PoCONUT) score in hepatocellular carcinoma (HCC) remains unknown. This study assessed whether PoCONUT score could serve as a useful predictor of survival for patients with small HCC.

Methods

547 consecutive patients with small HCC who underwent liver resection between February 2007 and December 2015 were included in this retrospective case-control study. Patients were categorized into two groups: low PoCONUT group (PoCONUT score ≤ 2, n = 382) and high PoCONUT group (PoCONUT score ≥ 3, n = 165). Propensity score matching (PSM) analysis was applied to balance the bias in baseline characteristics. A cumulative survival curve was established by the Kaplan–Meier method, and differences in OS and RFS among CONUT score groups were determined by the log rank test. Cox proportional hazard regression analysis was used to evaluate the association of PoCONUT score and overall survival (OS) and recurrence-free survival (RFS), with calculation of hazard ratios (HRs) and 95 % confidence intervals (95 % CIs).

Results

Cox proportional hazard regression analysis suggested that the PoCONUT score was an independent risk factor for both OS and RFS in patients with small HCC before and after PSM.

Conclusions

High PoCONUT score helps to predict worse OS and RFS in patients with small HCC who underwent liver resection.
Large-scale genomic analysis of antimicrobial resistance in the zoonotic pathogen Streptococcus suis
Authors: Hadjirin Nazreen F. , Miller Eric L. , Murray Gemma G. R. , Yen Phung L. K. , Phuc Ho D. , Wileman Thomas M. , Hernandez-Garcia Juan , Williamson Susanna M. , Parkhill Julian , Maskell Duncan J. , Zhou Rui , Fittipaldi Nahuel , Gottschalk Marcelo , Tucker A. W. , Hoa Ngo Thi , Welch John J. , Weinert Lucy A.
Published: September 2021

Background

Antimicrobial resistance (AMR) is among the gravest threats to human health and food security worldwide. The use of antimicrobials in livestock production can lead to emergence of AMR, which can have direct effects on humans through spread of zoonotic disease. Pigs pose a particular risk as they are a source of zoonotic diseases and receive more antimicrobials than most other livestock. Here we use a large-scale genomic approach to characterise AMR inStreptococcus suis, a commensal found in most pigs, but which can also cause serious disease in both pigs and humans.

Results

We obtained replicated measures of Minimum Inhibitory Concentration (MIC) for 16 antibiotics, across a panel of 678 isolates, from the major pig-producing regions of the world. For several drugs, there was no natural separation into ‘resistant’ and ‘susceptible’, highlighting the need to treat MIC as a quantitative trait. We found differences in MICs between countries, consistent with their patterns of antimicrobial usage. AMR levels were high even for drugs not used to treatS. suis, with many multidrug-resistant isolates. Similar levels of resistance were found in pigs and humans from regions associated with zoonotic transmission. We next used whole genome sequences for each isolate to identify 43 candidate resistance determinants, 22 of which were novel inS. suis. The presence of these determinants explained most of the variation in MIC. But there were also interesting complications, including epistatic interactions, where known resistance alleles had no effect in some genetic backgrounds. Beta-lactam resistance involved many core genome variants of small effect, appearing in a characteristic order.

Conclusions

We present a large dataset allowing the analysis of the multiple contributing factors to AMR inS. suis. The high levels of AMR inS. suisthat we observe are reflected by antibiotic usage patterns but our results confirm the potential for genomic data to aid in the fight against AMR.
Early life and socio-economic determinants of dietary trajectories in infancy and early childhood – results from the HSHK birth cohort study
Authors: Manohar Narendar , Hayen Andrew , Do Loc , Scott Jane , Bhole Sameer , Arora Amit
Published: September 2021

Background

Early childhood is a period when dietary behaviours are established. This study aimed to examine the longitudinal intake of core and discretionary foods and identify early life and socio-economic factors influencing those intakes.

Methods

Mother-infant dyads (n = 934) from the Healthy Smiles Healthy Kids study, an ongoing birth cohort study, were interviewed. The information on ‘weekly frequency of core and discretionary foods intake’ using a food frequency questionnaire was collected at 4 months, 8 months, 1 year, 2 years and 3 years age points. Group-based trajectory modelling analyses were performed to identify diet trajectories for ‘core’ and ‘discretionary’ foods respectively. A multinomial logistic regression was performed to identify the maternal and child-related predictors of resulting trajectories.

Results

The intake of core and discretionary foods each showed distinct quadratic (n = 3) trajectories with age. Overall, core foods intake increased rapidly in the first year of life, followed by a decline after age two, whereas discretionary foods intake increased steadily across the five age points. Multiparity (Relative Risk (RR): 0.46, 95%CI: 0.27–0.77), non-English speaking ethnicity of mother (RR: 0.66, 95%CI: 0.47–0.91) and having a single mother (RR: 0.40, 95%CI: 0.18–0.85) were associated with low trajectories of core foods intake whereas older maternal age (RR: 1.05, 95%CI: 1.01–1.08) and longer breastfeeding duration (RR: 1.02, 95%CI: 1.00–1.03) were associated with higher trajectories of core foods intake. Also, multiparity (RR 2.63, 95%CI: 1.47–4.70), low maternal education (RR 3.01, 95%CI: 1.61–5.65), and socio-economic disadvantage (RR 2.69, 95%CI: 1.31–5.55) were associated with high trajectories of discretionary foods intake. Conversely, longer duration of breastfeeding (RR 0.99, 95%CI: 0.97–0.99), and timely introduction of complementary foods (RR 0.30, 95%CI: 0.15–0.61) had a protective effect against high discretionary foods consumption in infancy and early childhood.

Conclusion

Children’s frequency of discretionary foods intake increases markedly as they transition from infancy to preschool age, and the trajectories of intake established during early childhood are strongly influenced by socio-demographic factors and infant feeding choices. Hence, there is a need for targeted strategies to improve nutrition in early childhood and ultimately prevent the incidence of chronic diseases in children.
Impact of taxes on purchases of close substitute foods: analysis of cross-price elasticities using data from a randomized experiment
Authors: Hoenink Jody C. , Waterlander Wilma E. , Mackenbach Joreintje D. , Mhurchu Cliona Ni , Wilson Nick , Beulens Joline W. J. , Nghiem Nhung
Published: September 2021

Objective

To examine the effects of health-related food taxes on substitution and complementary purchases within food groups, including from unhealthier to healthier alternatives and between brands.

Methods

We used data from a virtual supermarket experiment with data from 4,259 shopping events linked to varying price sets. Substitution or complementary effects within six frequently purchased food categories were analyzed. Products’ own- and cross-price elasticities were analyzed using Almost Ideal Demand System models.

Results

Overall, 37.5% of cross-price elasticities were significant (p < 0.05) and included values greater than 0.10. Supplementary and complementary effects were particularly found in the dairy, meats and snacks categories. For example, a 1% increase in the price of high saturated fat dairy was associated with a 0.18% (SE 0.06%) increase in purchases of low saturated fat dairy. For name- and home-brand products, significant substitution effects were found in 50% (n = 3) of cases, but only in one case this was above the 0.10 threshold.

Conclusions/policy implications

Given the relatively low own-price elasticities and the limited substitution and complementary effects, relatively high taxes are needed to substantively increase healthy food purchases at the population level.

Trial registration

This study included secondary analyses; the original trial was registered in the Australian New Zealand Clinical Trials Registry ACTRN12616000122459.
Effects of material hardship on depression among adults in South Korea: insights from by the Korea Welfare Panel Study 2008–2017
Authors: Kang Soo Hyun , Kim Selin , Park Eun-Cheol , Jang Sung-In
Published: September 2021

Background

Low socioeconomic status deemed by income-based measures is a risk factor for depression. Material hardship is commonly used as a multidimensional socioeconomic indicator to identify the struggles that low-income households encounter that are not captured by conventional income-based measures. The aim of this study was to examine the effect of material hardship on depression.

Methods

We used wave 3 (2008) to wave 12 (2017) panel data collected by the Korea Welfare Panel Study. The material hardship measure included six dimensions: food, housing, medical care, paying utility bills, education, and financial hardship. Depression was measured using the Center for Epidemiologic Studies Depression Scale (CESD-11). A generalised estimating equation model was applied to test the causal association between material hardship and log transferred CESD-11.

Results

The first time point comprised 3,866 participants. Those who continually experienced material hardship had higher depression scores (male: β = 2.82, female: β = 3.98, p-value: < .0001). Food hardship was the most critical risk factor (male: β = 3.29, female: β = 4.05, p-value: < .0001).

Conclusions

Material hardship is associated with increased risk of depression, especially food hardship. We should consider guaranteeing food security, and community and policy makers should consider material hardship in their approach when identifying low-income populations at high risk for depression.
Antimicrobial susceptibility patterns of respiratory Gram-negative bacterial isolates from COVID-19 patients in Switzerland
Authors: Gysin Marina , Acevedo Claudio Tirso , Haldimann Klara , Bodendoerfer Elias , Imkamp Frank , Bulut Karl , Buehler Philipp Karl , Brugger Silvio Daniel , Becker Katja , Hobbie Sven N.
Published: September 2021

Background

Bacterial superinfections associated with COVID-19 are common in ventilated ICU patients and impact morbidity and lethality. However, the contribution of antimicrobial resistance to the manifestation of bacterial infections in these patients has yet to be elucidated.

Methods

We collected 70 Gram-negative bacterial strains, isolated from the lower respiratory tract of ventilated COVID-19 patients in Zurich, Switzerland between March and May 2020. Species identification was performed using MALDI-TOF; antibiotic susceptibility profiles were determined by EUCAST disk diffusion and CLSI broth microdilution assays. Selected Pseudomonas aeruginosa isolates were analyzed by whole-genome sequencing.

Results

Pseudomonas aeruginosa (46%) and Enterobacterales (36%) comprised the two largest etiologic groups. Drug resistance in P. aeruginosa isolates was high for piperacillin/tazobactam (65.6%), cefepime (56.3%), ceftazidime (46.9%) and meropenem (50.0%). Enterobacterales isolates showed slightly lower levels of resistance to piperacillin/tazobactam (32%), ceftriaxone (32%), and ceftazidime (36%). All P. aeruginosa isolates and 96% of Enterobacterales isolates were susceptible to aminoglycosides, with apramycin found to provide best-in-class coverage. Genotypic analysis of consecutive P. aeruginosa isolates in one patient revealed a frameshift mutation in the transcriptional regulator nalC that coincided with a phenotypic shift in susceptibility to β-lactams and quinolones.

Conclusions

Considerable levels of antimicrobial resistance may have contributed to the manifestation of bacterial superinfections in ventilated COVID-19 patients, and may in some cases mandate consecutive adaptation of antibiotic therapy. High susceptibility to amikacin and apramycin suggests that aminoglycosides may remain an effective second-line treatment of ventilator-associated bacterial pneumonia, provided efficacious drug exposure in lungs can be achieved.
Role of autophagy on cancer immune escape
Authors: Duan Yalan , Tian Xiaoqing , Liu Qian , Jin Jianhua , Shi Juanjuan , Hou Yongzhong
Published: September 2021

Autophagy is catabolic process by degradation of intracellular components in lysosome including proteins, lipids, and mitochondria in response to nutrient deficiency or stress such as hypoxia or chemotherapy. Increasing evidence suggests that autophagy could induce immune checkpoint proteins (PD-L1, MHC-I/II) degradation of cancer cells, which play an important role in regulating cancer cell immune escape. In addition to autophagic degradation of immune checkpoint proteins, autophagy induction in immune cells (macrophages, dendritic cells) manipulates antigen presentation and T cell activity. These reports suggest that autophagy could negatively or positively regulate cancer cell immune escape by immune checkpoint protein and antigens degradation, cytokines release, antigens generation. These controversial phenomenon of autophagy on cancer cell immune evasion may be derived from different experimental context or models. In addition, autophagy maybe exhibit a role in regulating host excessive immune response. So rational combination with autophagy could enhance the efficacy of cancer immunotherapy. In this review, the current progress of autophagy on cancer immune escape is discussed.
Dose and engagement during an extended contact physical activity and dietary behavior change intervention delivered via tailored text messaging: exploring relationships with behavioral outcomes
Authors: Fjeldsoe Brianna S , Goode Ana D , Job Jennifer , Eakin Elizabeth G , Spilsbury Kate L , Winkler Elisabeth
Published: September 2021

Background

Extended contact interventions delivered via text messaging are a low-cost option for promoting the long-term continuation of behavior change. This secondary analysis of a text message–delivered extended contact intervention (‘Get Healthy, Stay Healthy’ (GHSH)) explores the extent to which changes in physical activity, dietary behaviors and body weight were associated with the frequency of text messages (dose) and contact between the health coach and participant (engagement).

Methods

Following a telephone coaching program, participants were randomised to receive extended contact via tailored text messages (GHSH, n = 114) or no additional contact (n = 114) over a 6-month period. Message dose, timing, and content were based on participant preferences, ascertained during two tailoring telephone calls. All incoming and outgoing messages were recorded. At baseline and 6 months, participants self-reported body weight and dietary behaviors (fruit and vegetable servings/day). Moderate-vigorous physical activity (MVPA) was assessed via accelerometry.

Results

Median dose (25th, 75th percentile) was 53 (33, 72) text messages in total across six months. Mean fortnightly dose in weeks 1–2 was 5.5 (95 % CI: 4.3, 6.6) text messages, and remained stable (with the exception of planned decreases in weeks involving additional intervention contacts). Offset against the average fortnightly dose of goal checks (1.6, 95 % CI: 1.3, 2.0 and 1.5, 95 % CI: 1.2, 1.8, for physical activity and diet respectively), mean replies to goal checks were highest in weeks 1–2 (1.4, 95 % CI: 1.4, 1.5 and 1.3, 95 % CI: 1.2, 1.4, respectively) and tended to become lower in most weeks thereafter. Greater weight loss was positively associated with text message dose (P = 0.022), with a difference of 1.9 kg between participants receiving the most and fewest texts. There was no association between engagement and changes in outcome measures.

Conclusions

A fixed dose of texts does not seem suitable to meet participants’ individual preferences. Higher self-selected text doses predicted better weight outcomes. However, greater participant engagement through text replies does not predict more favourable outcomes, despite being a suggested facilitator of successful behavior change maintenance.

Trial registration

Australian New Zealand Clinical Trials Registry number: ACTRN12613000949785. Date registered: 27 August 2013. Retrospectively registered. http://www.anzctr.org.au/.
A systematic review of providers’ experiences of facilitating group antenatal care
Authors: Lazar Jalana , Boned-Rico Laura , Olander Ellinor K. , McCourt Christine
Published: September 2021

Background

Group antenatal care is a rapidly expanding alternative antenatal care delivery model. Research has shown it to be a safe and effective care model for women, but less is known about the perspectives of the providers leading this care. This systematic review examined published literature that considered health care professionals’ experiences of facilitating group antenatal care.

Methods

Systematic searches were conducted in seven databases (Cinahl, Medline, Psychinfo, Embase, Ovid Emcare, Global Health and MIDRS) in April 2020. Qualitative or mixed methods studies with a significant qualitative component were eligible for inclusion if they included a focus on the experiences of health care providers who had facilitated group antenatal care. Prisma screening guidelines were followed and study quality was critically appraised by three independent reviewers. The findings were synthesised thematically.

Results

Nineteen papers from nine countries were included. Three main themes emerged within provider experiences of group antenatal care. The first theme, ‘Giving women the care providers feel they want and need’, addresses richer use of time, more personal care, more support, and continuity of care. The second theme, ‘Building skills and relationships’, highlights autonomy, role development and hierarchy dissolution. The final theme, ‘Value proposition of group antenatal care’, discusses provider investment and workload.

Conclusions

Health care providers’ experience of delivering group antenatal care was positive overall. Opportunities to deliver high-quality care that benefits women and allows providers to develop their professional role were appreciated. Questions about the providers’ perspectives on workload, task shifting, and the structural changes needed to support the sustainability of group antenatal care warrant further exploration.
The worldwide investigating nurses’ attitudes towards do-not-resuscitate order: a review
Authors: Raoofi Neda , Raoofi Samira , Jalali Rostam , Abdi Alireza , Salari Nader
Published: September 2021

Background

The acceptance or practical application of the do-not-resuscitate order is substantially dependent on internal or personal factors; in a way that decision-making about this issue can be specific to each person. Moreover, most nurses feel morally and emotionally stressed and confused during the process decision-making regarding DNR order. Therefore, the purpose of the present study was to evaluate nurses’ attitudes towards DNR order in a systematic review.

Methods

This critical survey was conducted using a systematic review protocol. To this end, the most relevant articles published in domestic and foreign databases with no time limits until October 2018 were searched. The inclusion and exclusion criteria were articles on DNR order, studies about nurses’ attitudes, descriptive and analytical research papers, as well as those with download links and full texts. The given articles were also assessed in terms of their quality and their main results were extracted.

Results

Of the total number of 1663 articles searched in the process of systematic review to investigate nurses’ attitudes towards DNR order, 88 articles were included in the full-text review step and finally 10 articles, meeting the inclusion criteria, were found. Assessing the quality of articles included in this review showed that 8 articles, in general, were of good quality and 2 studies were characterized with moderate quality. The main factors associated with nurses’ attitudes towards DNR order were grouped into three categories of (1) nurses’ attitudes towards DNR order, (2) guidelines for DNR order, and (3) decision-making by patients and their families about DNR order. In most of the studies examined, nurses’ attitudes towards DNR order were reported positive.

Conclusion

It seemed that nurses were willing to get involved in DNR order and each hospital was recommended to develop a written DNR policy directing individuals and avoiding their confusion in this respect.
Neuromedin U induces an invasive phenotype in CRC cells expressing the NMUR2 receptor
Authors: Przygodzka Patrycja , Sochacka Ewelina , Soboska Kamila , Pacholczyk Marcin , Papiewska-Pająk Izabela , Przygodzki Tomasz , Płociński Przemysław , Ballet Steven , De Prins An , Boncela Joanna
Published: September 2021

Background

Successful colorectal cancer (CRC) therapy often depends on the accurate identification of primary tumours with invasive potential. There is still a lack of identified pathological factors associated with disease recurrence that could help in making treatment decisions. Neuromedin U (NMU) is a secretory neuropeptide that was first isolated from the porcine spinal cord, and it has emerged as a novel factor involved in the tumorigenesis and/or metastasis of many types of cancers. Previously associated with processes leading to CRC cell invasiveness, NMU has the potential to be a marker of poor outcome, but it has not been extensively studied in CRC.

Methods

Data from The Cancer Genome Atlas (TCGA) were used to analyseNMUand NMU receptor (NMUR1andNMUR2) expression in CRC tissues vs. normal tissues, and real-time PCR was used forNMUand NMU receptor expression analysis. NMU protein detection was performed by immunoblotting. Secreted NMU was immunoprecipitated from cell culture-conditioned media and analysed by immunoblotting and protein sequencing. DNA demethylation by 5-aza-CdR was used to analyse the regulation ofNMUR1andNMUR2expression. NMU receptor activity was monitored by detecting calcium mobilisation in cells loaded with fluo-4, and ERK1/2 kinase activation was detected after treatment with NMU or receptor agonist. Cell migration and invasion were investigated using membrane filters. Integrin expression was evaluated by flow cytometry.

Results

The obtained data revealed elevated expression ofNMUandNMUR2in CRC tissue samples and variable expression in the analysed CRC cell lines. We have shown, for the first time, that NMUR2 activation induces signalling in CRC cells and that NMU increases the motility and invasiveness ofNMUR2-positive CRC cells and increases prometastatic integrin receptor subunit expression.

Conclusions

Our results show the ability of CRC cells to respond to NMU via activation of the NMUR2 receptor, which ultimately leads to a shift in the CRC phenotype towards a more invasive phenotype.
SUPERGNOVA: local genetic correlation analysis reveals heterogeneous etiologic sharing of complex traits
Authors: Zhang Yiliang , Lu Qiongshi , Ye Yixuan , Huang Kunling , Liu Wei , Wu Yuchang , Zhong Xiaoyuan , Li Boyang , Yu Zhaolong , Travers Brittany G. , Werling Donna M. , Li James J. , Zhao Hongyu
Published: September 2021

Local genetic correlation quantifies the genetic similarity of complex traits in specific genomic regions. However, accurate estimation of local genetic correlation remains challenging, due to linkage disequilibrium in local genomic regions and sample overlap across studies. We introduce SUPERGNOVA, a statistical framework to estimate local genetic correlations using summary statistics from genome-wide association studies. We demonstrate that SUPERGNOVA outperforms existing methods through simulations and analyses of 30 complex traits. In particular, we show that the positive yet paradoxical genetic correlation between autism spectrum disorder and cognitive performance could be explained by two etiologically distinct genetic signatures with bidirectional local genetic correlations.
Efficacy of low-dose fipronil bait against blacklegged tick (Ixodes scapularis) larvae feeding on white-footed mice (Peromyscus leucopus) under simulated field conditions
Authors: Poché David M. , Dawson Kelsey , Tseveenjav Batchimeg , Poché Richard M.
Published: September 2021

Background

Lyme disease, caused primarily byBorrelia burgdorferisensu stricto, is the most prevalent vector-borne disease in the United States. Treatment of rodent pathogen reservoirs with an oral acaricide may suppress the production of infected host-seeking ticks posing a risk for human infection. A previous study showed that an oral fipronil bait effectively controlled larvalIxodes scapularisticks on white-footed mice (Peromyscus leucopus) up to 15 days post-bait exposure. The present study expands upon this finding by exposing group-housed white-footed mice to fipronil bait under simulated field conditions prior to tick infestation.

Methods

Mice (n = 80) were housed in groups of 10 within large enclosures and offered a choice between fipronil bait within a commercial bait station and an alternative diet. The mice were assigned to two treatment groups and two control groups to undergo bait exposure durations of either 24 h (reduced) or 168 h (extended). Groups were further differentiated by the time point post-bait exposure when larval ticks were applied to mice within feeding capsules (reduced day 1, day 15; extended day 21, day 35). For 4 days post-tick introduction, attached larvae were observed by microscopy and replete larvae were recovered. Replete larvae were monitored for molting success. Plasma was collected from all treatment group mice to obtain fipronil plasma concentrations (CP).

Results

The fipronil bait (0.005% fipronil) was palatable and controlled larval ticks on white-footed mice when presented under simulated field conditions. Efficacy in preventing attached larvae from feeding to repletion was 100% (day 1), 89.0% (day 15), 85.8% (day 21), and 75.2% (day 35). When also considering molting success, the fipronil bait prevented 100% (day 1), 91.1% (day 15), 91.7% (day 21), and 82.5% (day 35) of larvae attaching to mice from molting. The mean CP per mouse was 191.5 ng/ml (day 1), 29.4 ng/ml (day 15), 10.6 ng/ml (day 21), and 1.0 ng/ml (day 35).

Conclusions

The results suggest that fipronil bait will be consumed by white-footed mice in the presence of an alternative diet, and effectively control larval ticks on treated mice. A field trial is needed to confirm the results of this study. Low-dose fipronil bait may provide a cost-effective means of controlling blacklegged ticks to be integrated into tick management programs.

Graphical Abstract
Babesiosis as a potential threat for bovine production in China
Authors: He Lan , Bastos Reginaldo G. , Sun Yali , Hua Guohua , Guan Guiquan , Zhao Junlong , Suarez Carlos E.
Published: September 2021

Babesiosis is a tick-borne disease with global impact caused by parasites of the phylum Apicomplexa, genus Babesia. Typically, acute bovine babesiosis (BB) is characterized by fever, anemia, hemoglobinuria, and high mortality. Surviving animals remain persistently infected and become reservoirs for parasite transmission. Bovids in China can be infected by one or more Babesia species endemic to the country, including B. bovis, B. bigemina, B. orientalis, B. ovata, B. major, B. motasi, B. U sp. Kashi and B. venatorum. The latter may pose a zoonotic risk. Occurrence of this wide diversity of Babesia species in China may be due to a combination of favorable ecological factors, such as the presence of multiple tick vectors, including Rhipicephalus and Hyalomma, the coexistence of susceptible bovid species, such as domestic cattle, yaks, and water buffalo, and the lack of efficient measures of tick control. BB is currently widespread in several regions of the country and a limiting factor for cattle production. While some areas appear to have enzootic stability, others have considerable cattle mortality. Research is needed to devise solutions to the challenges posed by uncontrolled BB. Critical research gaps include risk assessment for cattle residing in endemic areas, understanding factors involved in endemic stability, evaluation of parasite diversity and pathogenicity of regional Babesia species, and estimation of whether and how BB should be controlled in China. Research should allow the design of comprehensive interventions to improve cattle production, diminish the risk of human infections, and increase the availability of affordable animal protein for human consumption in China and worldwide. In this review, we describe the current state of BB with reference to the diversity of hosts, vectors, and parasite species in China. We also discuss the unique risks and knowledge gaps that should be taken into consideration for future Babesia research and control strategies.