bluuebunny/crossref_metadata_2025 huggingface dataset:
Unique adaptations in neonatal hepatic transcriptome, nutrient signaling, and one-carbon metabolism in response to feeding ethyl cellulose rumen-protected methionine during late-gestation in Holstein cows
Authors: Palombo Valentino , Alharthi Abdulrahman , Batistel Fernanda , Parys Claudia , Guyader Jessie , Trevisi Erminio , D’Andrea Mariasilvia , Loor Juan J.
Published: April 2021

Background

Methionine (Met) supply during late-pregnancy enhances fetal development in utero and leads to greater rates of growth during the neonatal period. Due to its central role in coordinating nutrient and one-carbon metabolism along with immune responses of the newborn, the liver could be a key target of the programming effects induced by dietary methyl donors such as Met. To address this hypothesis, liver biopsies from 4-day old calves (n = 6/group) born to Holstein cows fed a control or the control plus ethyl-cellulose rumen-protected Met for the last 28 days prepartum were used for DNA methylation, transcriptome, metabolome, proteome, and one-carbon metabolism enzyme activities.

Results

Although greater withers and hip height at birth in Met calves indicated better development in utero, there were no differences in plasma systemic physiological indicators. RNA-seq along with bioinformatics and transcription factor regulator analyses revealed broad alterations in ‘Glucose metabolism’, ‘Lipid metabolism, ‘Glutathione’, and ‘Immune System’ metabolism due to enhanced maternal Met supply. Greater insulin sensitivity assessed via proteomics, and efficiency of transsulfuration pathway activity suggested beneficial effects on nutrient metabolism and metabolic-related stress. Maternal Met supply contributed to greater phosphatidylcholine synthesis in calf liver, with a role in very low density lipoprotein secretion as a mechanism to balance metabolic fates of fatty acids arising from the diet or adipose-depot lipolysis. Despite a lack of effect on hepatic amino acid (AA) transport, a reduction in metabolism of essential AA within the liver indicated an AA ‘sparing effect’ induced by maternal Met.

Conclusions

Despite greater global DNA methylation, maternal Met supply resulted in distinct alterations of hepatic transcriptome, proteome, and metabolome profiles after birth. Data underscored an effect on maintenance of calf hepatic Met homeostasis, glutathione, phosphatidylcholine and taurine synthesis along with greater efficiency of nutrient metabolism and immune responses. Transcription regulators such asFOXO1,PPARG,E2F1, andCREB1appeared central in the coordination of effects induced by maternal Met. Overall, maternal Met supply induced better immunometabolic status of the newborn liver, conferring the calf a physiologic advantage during a period of metabolic stress and suboptimal immunocompetence.
An enhanced photosynthesis and carbohydrate metabolic capability contributes to heterosis of the cotton (Gossypium hirsutum) hybrid ‘Huaza Mian H318’, as revealed by genome-wide gene expression analysis
Authors: Ding Yuanhao , Zhang Rui , Zhu Longfu , Wang Maojun , Ma Yizan , Yuan Daojun , Liu Nian , Hu Haiyan , Min Ling , Zhang Xianlong
Published: April 2021

Background

Heterosis has been exploited for decades in different crops due to resulting in dramatic increases in yield, but relatively little molecular evidence on this topic was reported in cotton.

Results

The elite cotton hybrid variety ‘Huaza Mian H318’ (H318) and its parental lines were used to explore the source of its yield heterosis. A four-year investigation of yield-related traits showed that the boll number of H318 showed higher stability than that of its two parents, both in suitable and unsuitable climate years. In addition, the hybrid H318 grew faster and showed higher fresh and dry weights than its parental lines at the seedling stage. Transcriptome analysis of seedlings identified 17,308 differentially expressed genes (DEGs) between H318 and its parental lines, and 3490 extremely changed DEGs were screened out for later analysis. Most DEGs (3472/3490) were gathered between H318 and its paternal line (4–5), and only 64 DEGs were found between H318 and its maternal line (B0011), which implied that H318 displays more similar transcriptional patterns to its maternal parent at the seedling stage. GO and KEGG analyses showed that these DEGs were highly enriched in photosynthesis, lipid metabolic, carbohydrate metabolic and oxidation-reduction processes, and the expression level of these DEGs was significantly higher in H318 relative to its parental lines, which implied that photosynthesis, metabolism and stress resistances were enhanced in H318.

Conclusion

The enhanced photosynthesis, lipid and carbohydrate metabolic capabilities contribute to the heterosis of H318 at the seedling stage, and establishes a material foundation for subsequent higher boll-setting rates in complex field environments.
GWAS of pod morphological and color characters in common bean
Authors: García-Fernández Carmen , Campa Ana , Garzón Alvaro Soler , Miklas Phil , Ferreira Juan Jose
Published: April 2021

Background

Common bean (Phaseolus vulgaris L.) is an important legume species which can be consumed as immature pods and dry seeds after re-hydration and cooking. Many genes and QTL, and epistatic interactions among them, condition pod morphological traits. However, not all them have been mapped or validated nor candidate genes proposed. We sought to investigate the genomic regions conditioning pod morphological and color characters through GWAS.

Results

Single and multi-locus genome wide association analysis was used to investigate pod traits for a set of 301 bean lines of the Spanish Diversity Panel (SDP). The SDP was genotyped with 32,812 SNPs obtained from Genotyping by Sequencing. The panel was grown in two seasons and phenotypic data were recorded for 17 fresh pods traits grouped in four pod characters: pod length, pod cross-section, pod color, and number of seeds per pod. In all, 23 QTL for pod length, 6 for cross-section, 18 for pod color, 6 for number of seeds per pod and 9 associated to two or more pod characters were detected. Most QTL were located in the telomeric region of chromosomes Pv01, Pv02, Pv04, Pv08, Pv09 and Pv10. Eighteen detected QTL co-localized with 28 previously reported QTL. Twenty-one potential candidate genes involving developmental processes were detected underlying 11 QTL for pod morphological characters, four of them homologous to A. thaliana genes FIS2, SPL10, TTG2 and AML4 affecting silique size. Eight potential candidate genes involved in pigment synthesis, were found underlying five QTL for pod color.

Conclusions

GWAS for pod morphological and color characters in the bean Spanish Diversity Panel revealed 62 QTL, 18 co-localized with previously reported QTL, and 16 QTL were underlain by 25 candidate genes. Overall 44 new QTL identified and 18 existing QTL contribute to a better understanding of the complex inheritance of pod size and color traits in common bean and open the opportunity for future validation works.
Effect of glutamine supplementation on cardiometabolic risk factors and inflammatory markers: a systematic review and meta-analysis
Authors: Hasani Motahareh , Mansour Asieh , Asayesh Hamid , Djalalinia Shirin , Mahdavi Gorabi Armita , Ochi Fatemeh , Qorbani Mostafa
Published: April 2021

Background

Evidence exists that glutamine plays multiple roles in glucose metabolism, insulin sensitivity, and anti-inflammatory effects. This systematic review and meta-analysis of controlled trials aimed to assess the effect of glutamine supplementation on cardio-metabolic risk factors and inflammatory markers.

Methods

The processes of systematic reviews and meta-analyses were performed according to the PRISMA checklist. PubMed, Web of Sciences, Cochrane library, and Scopus databases were search for relevant studies without time or language restrictions up to December 30, 2020. All randomized clinical trials which assessed the effect of glutamine supplementation on “glycemic indices”, “level of triglyceride, “and “inflammatory markers” were included in the study. The effect of glutamine supplementation on cardio-metabolic risk factors and inflammatory markers was assessed using a standardized mean difference (SMD) and 95% confidence interval (CI). Heterogeneity between among studies was assessed using Cochran Q-statistic and I-square. Random/fixed-effects meta-analysis method was used to estimate the pooled SMD. The risk of bias for the included trials was evaluated using the Cochrane quality assessment tool.

Results

In total, 12 studies that assessed the effect of glutamine supplementation on cardio-metabolic risk factors were included in the study. Meta-analysis showed that glutamine supplementation significantly decreased significantly serum levels of FPG [SMD: − 0.73, 95% CI − 1.35, − 0.11, I2: 84.1%] and CRP [SMD: − 0.58, 95% CI − 0.1, − 0.17, I2: 0%]. The effect of glutamine supplementation on other cardiometabolic risk factors was not statistically significant (P > 0.05).

Conclusion

Our findings showed that glutamine supplementation might have a positive effect on FPG and CRP; both of which are crucial as cardio-metabolic risk factors. However, supplementation had no significant effect on other cardio-metabolic risk factors.
Inhaled nitric oxide preserves ventricular function during resuscitation using a percutaneous mechanical circulatory support device in a porcine cardiac arrest model: an echocardiographic myocardial work analysis
Authors: Nix Christoph , Zayat Rashad , Ebeling Andreas , Goetzenich Andreas , Chandrasekaran Uma , Rossaint Rolf , Hatam Nima , Derwall Matthias
Published: April 2021

Background

Resuscitation using a percutaneous mechanical circulatory support device (iCPR) improves survival after cardiac arrest (CA). We hypothesized that the addition of inhaled nitric oxide (iNO) during iCPR might prove synergistic, leading to improved myocardial performance due to lowering of right ventricular (RV) afterload, left ventricular (LV) preload, and myocardial energetics. This study aimed to characterize the changes in LV and RV function and global myocardial work indices (GWI) following iCPR, both with and without iNO, using 2-D transesophageal echocardiography (TEE) and GWI evaluation as a novel non-invasive measurement.

Methods

In 10 pigs, iCPR was initiated following electrically-induced CA and 10 min of untreated ventricular fibrillation (VF). Pigs were randomized to either 20 ppm (20 ppm, n = 5) or 0 ppm (0 ppm, n = 5) of iNO in addition to therapeutic hypothermia for 5 h following ROSC. All animals received TEE at five pre-specified time-points and invasive hemodynamic monitoring.

Results

LV end-diastolic volume (LVEDV) increased significantly in both groups following CA. iCPR alone led to significant LV unloading at 5 h post-ROSC with LVEDV values reaching baseline values in both groups (20 ppm: 68.2 ± 2.7 vs. 70.8 ± 6.1 mL, p = 0.486; 0 ppm: 70.8 ± 1.3 vs. 72.3 ± 4.2 mL, p = 0.813, respectively). LV global longitudinal strain (GLS) increased in both groups following CA. LV-GLS recovered significantly better in the 20 ppm group at 5 h post-ROSC (20 ppm: − 18 ± 3% vs. 0 ppm: − 13 ± 2%, p = 0.025). LV-GWI decreased in both groups after CA with no difference between the groups. Within 0 ppm group, LV-GWI decreased significantly at 5 h post-ROSC compared to baseline (1,125 ± 214 vs. 1,835 ± 305 mmHg%, p = 0.011). RV-GWI was higher in the 20 ppm group at 3 h and 5 h post-ROSC (20 ppm: 189 ± 43 vs. 0 ppm: 108 ± 22 mmHg%, p = 0.049 and 20 ppm: 261 ± 54 vs. 0 ppm: 152 ± 42 mmHg%, p = 0.041). The blood flow calculated by the Impella controller following iCPR initiation correlated well with the pulsed-wave Doppler (PWD) derived pulmonary flow (PWD vs. controller: 1.8 ± 0.2 vs. 1.9 ± 0.2L/min, r = 0.85, p = 0.012).

Conclusions

iCPR after CA provided sufficient unloading and preservation of the LV systolic function by improving LV-GWI recovery. The addition of iNO to iCPR enabled better preservation of the RV-function as determined by better RV-GWI. Additionally, Impella-derived flow provided an accurate measure of total flow during iCPR.
A demonstration of using formal consensus methods within guideline development; a case study
Authors: Carter P. , O’Donoghue K. J. M. , Dworzynski K. , O’Shea L. , Roberts V. , Reeves T. , Bastounis A. , Mugglestone M. A. , Fawke J. , Pilling S.
Published: April 2021

Background

Recommendations within guidelines are developed by synthesising the best available evidence; when limited evidence is identified recommendations are generally based on informal consensus. However, there are potential biases in group decision making, and formal consensus methods may help reduce these.

Methods

We conducted a case study using formal consensus, to develop one set of recommendations within the Neonatal Parenteral Nutrition guideline being produced for the National Institute for Health and Care Excellence. Statements were generated through identification of published guidelines on several topics relating to neonatal parenteral nutrition. Ten high quality guidelines were included, and 28 statements were generated; these statements were rated by the committee via two rounds of voting. The statements which resulted in agreement were then used to develop the recommendations.

Results

The approach was systematic and provided transparency. Additionally, a number of lessons were learnt; including the value of selecting the appropriate topic, giving adequate time to the process, and ensuring methodologies are understood by the committee for their value and relevance.

Conclusion

Formal consensus is a valuable option for use within guideline development when specific criteria are met. The approach provides transparent methodology, ensuring clarity on how recommendations are developed.
Optimal timing of endoscopic retrograde cholangiopancreatography for acute cholangitis associated with distal malignant biliary obstruction
Authors: Park Namyoung , Lee Sang Hyub , You Min Su , Kim Joo Seong , Huh Gunn , Chun Jung Won , Cho In Rae , Paik Woo Hyun , Ryu Ji Kon , Kim Yong-Tae
Published: April 2021

Background

There is a lack of studies regarding the optimal timing for endoscopic retrograde cholangiopancreatography (ERCP) in patients with cholangitis caused by distal malignant biliary obstruction (MBO). This study aims to investigate the optimal timing of ERCP in patients with acute cholangitis associated with distal MBO with a naïve papilla.

Methods

A total of 421 patients with acute cholangitis, associated with distal MBO, were enrolled for this study. An urgent ERCP was defined as being an ERCP performed within 24 h following emergency room (ER) arrival, and early ERCP was defined as an ERCP performed between 24 and 48 h following ER arrival. We evaluated both 30-day and 180-day mortality as primary outcomes, according to the timing of the ERCP.

Results

The urgent ERCP group showed the lowest 30-day mortality rate (2.2%), as compared to the early and delayed ERCP groups (4.3% and 13.5%) (P < 0.001). The 180-day mortality rate was lowest in the urgent ERCP group, followed by early ERCP and delayed ERCP groups (39.4%, 44.8%, 60.8%; P = 0.006). A subgroup analysis showed that in both the primary distal MBO group, as well as in the moderate-to-severe cholangitis group, the urgent ERCP had significantly improved in both 30-day and 180-day mortality rates. However, in the secondary MBO and mild cholangitis groups, the difference in mortality rate between urgent, early, and delayed ERCP groups was not significant.

Conclusions

In patients with acute cholangitis associated with distal MBO, urgent ERCP might be helpful in improving the prognosis, especially in patients with primary distal MBO or moderate-to-severe cholangitis.
Small bowel obstruction and strangulation secondary to an adhesive internal hernia post ESWL for right ureteral calculi: a case report and review of literature
Authors: Gitonga Elaine N. , Shen Haitao
Published: April 2021

Background

Extracorporeal shock wave lithotripsy (ESWL) is a relatively safe and convenient mode of treatment for ureteral and renal stones, despite its relative safety; ESWL is not without its complications. We present a case of a patient we managed for small bowel obstruction and strangulation due to an adhesive internal hernia after ESWL was done because of right ureteral calculi.

Case presentation

We report a case of a 59-year-old patient who presented with severe abdominal pain a few hours after ESWL because of a right upper ureteric calculus. The abdominal pain increased in severity in time and became more generalized. The patient had one episode of gross hematochezia as she was being prepped for emergency laparotomy. Intra-op, she had a strangulated internal hernia because of an omental-mesenteric adhesion.

Conclusion

This case report hopes to highlight the potential of complications like acquired IH due to adhesions in patients with a history of ureteral calculi, and also the complications that may come about post-ESWL. Patients who present with signs of persistent abdominal pain post-ESWL should be vigilantly observed. If symptoms persist, increase in intensity or there is a general deterioration of the patients’ hemodynamic status, even in light of negative MDCT findings, prompt surgical intervention is crucial for definitive diagnosis as well as management.
Plasma interleukin-17 and alpha-fetoprotein combination effectively predicts imminent hepatocellular carcinoma occurrence in liver cirrhotic patients
Authors: Liang Kung-Hao , Lai Ming-Wei , Lin Yang-Hsiang , Chu Yu-De , Lin Chih-Lang , Lin Wey-Ran , Huang Ya-Hui , Wang Tong-Hung , Chien Rong-Nan , Hu Tsung-Hui , Yeh Chau-Ting
Published: April 2021

Background

Predicting imminent hepatocellular carcinoma (HCC) in liver cirrhotic patients is an unmet medical need. We aimed to investigate circulatory biomarkers and their optimum combinations in a prospective study.

Methods

We investigated plasma interleukin 17 (IL-17) concentrations, quantified using enzyme-linked immunosorbent assay (ELISA), for the prediction of HCC in a large cohort of 404 HCC-naïve liver cirrhotic patients regularly followed after recruitment. Additionally, IL-17 in surgically resected tumor tissues were evaluated using immunohistochemistry staining.

Results

IL-17 was detected in HCC tissues. The IL-17 concentrations in the peripheral blood do not have correlation with an extensive list of 31 common demographic, metabolic and liver function variables in the cohort of liver cirrhotic patients. Furthermore, patients stratified by IL-17 and alpha-fetoprotein (AFP) showed distinctive cumulative incidence of HCC. Imminent HCC, defined here as HCC occurrence within 1 year, can be predicted by IL-17 alone with an area under the receiver operating characteristic curve [AUC] of 0.762 (P = 0.002). An multivariate analysis showed that age, hepatitis C viral infection, AFP and IL-17 were four independent factors associated with imminent HCC (adjusted P = 0.03, 0.041, 0.024 and 0.008 respectively). An explicit risk score (R) combining the concentrations of two plasma biomarkers, AFP and IL-17, achieved a high AUC of 0.933 (95% confidence interval 0.893–0.972, P < 0.001) in predicting imminent HCC, with 100% sensitivity and 79.9% specificity at the optimum cutoff. The score is defined as: $${\text{R}} = (2.6914)*{\text{IL-17}} + (0.3909)*{\text{AFP}} - (0.80812875)*{\text{IL-17}}^{2} + (0.10288876884)*{\text{IL-17}}^{2} *{\text{AFP}}.$$

R
=

(
2.6914
)

∗
IL-17
+

(
0.3909
)

∗
AFP
-

(
0.80812875
)

∗

IL-17

2

+

(
0.10288876884
)

∗

IL-17

2

∗
AFP
.

Conclusions

The circulatory IL-17 concentration is a predictor of subsequent HCC occurrence in liver cirrhotic patients. The combination of AFP and IL-17 is highly effective in predicting imminent HCC within 1 year.
Malnutrition and depression as predictors for 30-day unplanned readmission in older patient: a prospective cohort study to develop 7-point scoring system
Authors: Fitriana Ika , Setiati Siti , Rizal Edy W , Istanti Rahmi , Rinaldi Ikhwan , Kojima Taro , Akishita Masahiro , Azwar Muhammad Khifzhon
Published: April 2021

Background

Readmission is related to high cost, high burden, and high risk for mortality in geriatric patients. A scoring system can be developed to predict the readmission of older inpatients to perform earlier interventions and prevent readmission.

Methods

We followed prospectively inpatients aged 60 years and older for 30 days, with initial comprehensive geriatric assessment (CGA) on admission in a tertiary referral centre. Patients were assessed with CGA tools consisting of FRAIL scale (fatigue, resistance, ambulation, illness, loss of weight), the 15-item Geriatric Depression Scale, Mini Nutritional Assessment short-form (MNA-SF), the Barthel index for activities of daily living (ADL), Charlson Comorbidity Index (CCI), caregiver burden based on 4-item Zarit Burden Index (ZBI), and cognitive problem with Abbreviated Mental Test (AMT). Demographic data, malignancy diagnosis, and number of drugs were also recorded. We excluded data of deceased patients and patients transferred to other hospitals. We conducted stepwise multivariate regression analysis to develop the scoring system.

Results

Thirty-day unplanned readmission rate was 37.6 %. Among 266 patients, 64.7 % of them were malnourished, and 46.5 % of them were readmitted. About 24 % were at risk for depression or having depressed mood, and 53.1 % of them were readmitted. In multivariate analysis, nutritional status (OR 2.152, 95 %CI 1.151–4.024), depression status (OR 1.884, 95 %CI 1.071–3.314), malignancy (OR 1.863 95 %CI 1.005–3.451), and functional status (OR 1.584, 95 %CI 0.885–2.835) were included in derivation of 7 score system. The scoring system had maximum score of 7 and incorporated malnutrition (2 points), depression (2 points), malignancy (2 points), and dependent functional status (1 point). A score of 3 or higher suggested 82 % probability of readmission within 30 days following discharge. Area under the curve (AUC) was 0.694 (p = 0.001).

Conclusions

Malnutrition, depression, malignancy and functional problem are predictors for 30-day readmission. A practical CGA-based 7 scoring system had moderate accuracy and strong calibration in predicting 30-day unplanned readmission for older patients.
Association between housing environment and depressive symptoms among older people: a multidimensional assessment
Authors: Chen Yuan , Cui Ping Yu , Pan Yi Yang , Li Ya Xing , Waili Nuremaguli , Li Ying
Published: April 2021

Background

Depression is a common mental disorder among older people. This study aimed to assess the association between housing environment factors and depressive symptoms among older people using a multidimensional assessment method.

Methods

The study uses a population-based cross-sectional design. A total of 950 participants aged ≥ 60 years were selected using a complex multistage sampling design from 22 locations in China. All data were collected using questionnaires by face-to-face interviews. A total of 938 participants were included in the analysis, and 17.1% of males and 23.1% of females were identified as having depressive symptoms. The depressive symptoms were assessed using the 15-item Geriatric Depression Scale. The housing environment was assessed on the basis of four dimensions: physical, social, psychological, and cognition and physical function. Cumulative logistic regression analysis was used to evaluate the association between housing environment and depressive symptoms.

Results

The Cochran–Armitage trend test showed that the depressive symptom scores were linearly negatively associated with self-assessed housing environment, living arrangement, life satisfaction, and other physical environment factors and linearly positively associated with cognitive and physical function scores. The results of cumulative logistic regression analysis showed that the housing environment was significantly associated with depressive symptoms. The participants’ self-assessed housing environment was strongly associated with the levels of depressive symptom scores, and the odds ratio was 3.47 (95% CI, 1.14–10.82, P = 0.003).

Conclusion

The housing environment was significantly associated with depressive symptoms. Our results suggest that multi-dimensional assessment in the housing environment may be an effective way to develop intervention strategies of depressive symptoms among older people.
High frequency of Taenia solium antigen positivity in patients admitted for neurological disorders in the Rural Hospital of Mosango, Democratic Republic of Congo
Authors: Mukendi Deby , Kalo Jean-Roger Lilo , Lutumba Pascal , Barbé Barbara , Jacobs Jan , Yansouni Cedric P. , Gabriël Sarah , Dorny Pierre , Chappuis François , Boelaert Marleen , Winkler Andrea S. , Verdonck Kristien , Bottieau Emmanuel
Published: April 2021

Background

The epidemiology of human cysticercosis and neurocysticercosis, caused by the larval stage of the pork tapeworm Taenia solium, is not well known in the Democratic Republic of Congo (DRC). Within a multicenter etiological and diagnostic study conducted by the NIDIAG consortium (“Better Diagnosis for Neglected Infections”) and investigating several challenging syndromes, we consecutively evaluated from 2012 to 2015 all patients older than 5 years presenting with neurological disorders (neurology cohort) and with fever > 7 days (persistent fever cohort) at the rural hospital of Mosango, province of Kwilu, DRC. In both cohorts, etiological diagnosis relied on a systematic set of reference laboratory assays and on pre-established clinical case definitions. No neuroimaging was available in the study hospital. In this study, we determined the frequency of T. solium infection in both cohorts and explored in the neurology cohort its association with specific neurological presentations and final etiological diagnoses.

Methods

We conducted a post-hoc descriptive and analytic study on cysticercosis in the neurology and persistent fever cohorts, based on the presence in serum samples of circulating T. solium antigen using the B158/B60 enzyme-linked immunosorbent assay (ELISA) and of cysticercosis IgG using the LDBIO Cysticercosis Western Blot IgG assay.

Results

For the neurology cohort, 340 samples (of 351 enrolled patients) were available for analysis (males: 46.8%; mean age: 38.9 years). T. solium antigen positivity was found in 43 participants (12.6%; 95% confidence interval [CI] 9.3–16.7%), including 9 of 60 (15%) patients with epilepsy. Among the 148 samples available from the persistent fever cohort (males: 39.9%; mean age: 19.9 years), 7 were positive in the T. solium antigen ELISA (4.7%; 95% CI 1.9–9.5%; P = 0.009 when compared to the neurology cohort). No significant association was found within the neurology cohort between positivity and clinical presentation or final diagnoses. Of note, the IgG antibody-detecting assay was found positive in only four (1.3%) of the participants of the neurology cohort and in none of the persistent fever cohort.

Conclusions

T. solium antigen positivity was found in at least 10% of patients admitted with neurological disorders in the Kwilu province, DRC, with no specific pattern of presentation. Further neuroimaging studies should be used to confirm whether neurocysticercosis is prevalent in this region.
Virulence genes and phylogenetic groups of uropathogenic Escherichia coli isolates from patients with urinary tract infection and uninfected control subjects: a case-control study
Authors: Rezatofighi Seyedeh Elham , Mirzarazi Mahsa , Salehi Mansour
Published: April 2021

Background

Urinary Tract Infection (UTI) is one of the most common bacterial infectious diseases which causes considerable morbidity and costly health problems. Uropathogenic Escherichia coli (UPEC), the most common pathogen causing UTI, is a highly heterogeneous group of extraintestinal pathogenic E. coli (ExPEC) which may carry a variety of virulence factors and belonging to different phylogenetic backgrounds. The current study aimed to investigate the frequency and association between various virulence factors (VFs) and phylogenetic groups of UPEC and commensal isolates.

Methods

UPEC and commensal E. coli strains isolated from UTI and feces of healthy humans were compared for the presence of VFs and phylogenetic groups. Association between virulence genes was investigated and cluster analysis was employed.

Results

According to the results, among a 30 virulence markers tested, the pathogenicity-associated island (PAI), papAH, papEF, fimH, fyuA, and traT genes prevalence were statistically significant in UPEC isolates. A strong association was found between the B2 and D phylogenetic groups and clinical isolates of UPEC; while, commensal isolates were mostly associated with phylogenetic group A. The aggregated VFs scores were more than twice higher in the UPEC isolates in comparison with the commensal isolates. Interestingly, the B2 group in both UPEC and commensal isolates had the highest VF scores. A strong positive association was found between several virulence genes. The clustering results demonstrated that UPEC or commensal E. coli isolates were highly heterogeneous due to different composition of their virulence gene pool and pathogenicity islands.

Conclusion

Genetic structure and VFs of UPEC strains vary from region to region; therefore, to control the UTI, the epidemiological aspects and characterization of the UPEC isolates need to be investigated in different regions. Since UPEC isolates are generally originate from the commensal strains, it may be feasible to reduce the UTI burden by interfering the intestinal colonization, particularly in the highly pathogenic clonal lineages such as B2.
Correlation between quantitative perfusion histogram parameters of DCE-MRI and PTEN, P-Akt and m-TOR in different pathological types of lung cancer
Authors: Zhang Bingqian , Zhao Zhenhua , Huang Ya’nan , Mao Haijia , Zou Mingyue , Wang Cheng , Yu Guangmao , Zhang Minming
Published: April 2021

Background

To explore if the quantitative perfusion histogram parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlates with the expression of PTEN, P-Akt and m-TOR protein in lung cancer.

Methods

Thirty‐three patients with 33 lesions who had been diagnosed with lung cancer were enrolled in this study. They were divided into three groups: squamous cell carcinoma (SCC, 15 cases), adenocarcinoma (AC, 12 cases) and small cell lung cancer (SCLC, 6 cases). Preoperative imaging (conventional imaging and DCE-MRI) was performed on all patients. The Exchange model was used to measure the phar- macokinetic parameters, including Ktrans, Vp, Kep, Ve and Fp, and then the histogram parameters meanvalue, skewness, kurtosis, uniformity, energy, entropy, quantile of above five parameters were analyzed. The expression of PTEN, P-Akt and m-TOR were assessed by immunohistochemistry. Spearman correlation analysis was used to compare the correlation between the quantitative perfusion histogram parameters and the expression of PTEN, P-Akt and m-TOR in different pathological subtypes of lung cancer.

Results

The expression of m-TOR (P = 0.013) and P-Akt (P = 0.002) in AC was significantly higher than those in SCC. Vp (uniformity) in SCC group, Ktrans (uniformity), Ve (kurtosis, Q10, Q25) in AC group, Fp (skewness, kurtosis, energy), Ve (Q75, Q90, Q95) in SCLC group was positively correlated with PTEN, and Fp (entropy) in the SCLC group was negatively correlated with PTEN (P < 0.05); Kep (Q5, Q10) in the SCLC group was positively correlated with P-Akt, and Kep (energy) in the SCLC group was negatively correlated with P-Akt (P < 0.05); Kep (Q5) in SCC group and Vp (meanvalue, Q75, Q90, Q95) in SCLC group was positively correlated with m-TOR, and Ve (meanvalue) in SCC group was negatively correlated with m-TOR (P < 0.05).

Conclusions

The quantitative perfusion histogram parameters of DCE-MRI was correlated with the expression of PTEN, P-Akt and m-TOR in different pathological types of lung cancer, which may be used to indirectly evaluate the activation status of PI3K/Akt/mTOR signal pathway gene in lung cancer, and provide important reference for clinical treatment.
German translation, cultural adaptation and validation of the unidimensional self-efficacy scale for multiple sclerosis
Authors: Seebacher Barbara , Mills Roger J. , Reindl Markus , Zamarian Laura , Kircher Simone , Brenneis Christian , Ehling Rainer , Deisenhammer Florian
Published: April 2021

Background

Self-efficacy concerns individuals’ beliefs in their capability to exercise control in specific situations and complete tasks successfully. In people with multiple sclerosis (PwMS), self-efficacy has been associated with physical activity levels and quality of life. As a validated German language self-efficacy scale for PwMS is missing the aims of this study were to translate the Unidimensional Self-Efficacy Scale for Multiple Sclerosis (USE-MS) into German, establish face and content validity and cultural adaptation of the German version for PwMS in Austria. A further aim was to validate the German USE-MS (USE-MS-G) in PwMS.

Methods

Permission to translate and validate the USE-MS was received from the scale developers. Following guidelines for translation and validation of questionnaires and applying Bandura’s concept of self-efficacy, the USE-MS was forward-backward translated with content and face validity established. Cultural adaptation for Austria was performed using cognitive patient interviews. Reliability was assessed using Cronbach’s alpha, Person separation index and Lin’s concordance correlation coefficient. Rasch analysis was employed to assess construct validity. Comparison was made to scales for resilience, general self-efficacy, anxiety and depression, multiple sclerosis fatigue and health-related quality of life. Data were also pooled with an historic English dataset to compare the English and German language versions.

Results

The translation and cultural adaptation were successfully performed in the adaptation process of the USE-MS-G. Pretesting was conducted in 30 PwMS, the validation of the final USE-MS-G involved 309 PwMS with minimal to severe disability. The USE-MS-G was found to be valid against the Rasch model when fitting scale data using a bifactor solution of two super-items. It was shown to be unidimensional, free from differential item functioning and well targeted to the study population. Excellent convergent and known-groups validity, internal consistency, person separation reliability and test-retest reliability were shown for the USE-MS-G. Pooling of the English and German datasets confirmed invariance of item difficulties between languages.

Conclusion

The USE-MS-G is a robust, valid and reliable scale to assess self-efficacy in PwMS and can generate interval level data on an equivalent metric to the UK version.

Trial registration

ISRCTN Registry; ISRCTN14843579; prospectively registered on 02. 01. 2019.
Abnormal placental perfusion and the risk of stillbirth: a hospital-based retrospective cohort study
Authors: Wu Jiang-Nan , Ren Yun-Yun , Zhu Chen , Peng Ting , Zhang Bin , Li Ming-Qing
Published: April 2021

Background

A lack of information on specific and interventional factors for stillbirth has made designing preventive strategies difficult, and the stillbirth rate has declined more slowly than the neonatal death rate. We compared the prevalence of stillbirth among the offspring of women with or without abnormal placental perfusion (APP).

Methods

We conducted a hospital-based retrospective cohort study involving women with a singleton pregnancy between 2012 and 2016 (N = 41,632). Multivariate analysis was performed to compare the prevalence of stillbirth in infants exposed to APP (defined as any abnormality in right or left uterine artery pulsatility index or resistance index [UtA-PI, −RI] [e.g., > 95th percentile] or presence of early diastolic notching) with that in those not exposed to APP.

Results

Stillbirths were more common among women with APP than among those with normal placental perfusion (stillbirth rate, 4.3 ‰ vs 0.9 ‰; odds ratio (OR), 4.2; 95% confidence interval (CI), 2.2 to 8.0). The association strengths were consistent across groups of infants exposed to APP that separately defined by abnormality in right or left UtA-PI or -RI (OR ranged from 3.2 to 5.3; all P ≤ 0.008). The associations were slightly stronger for the unexplained stillbirths. Most of the unexplained stillbirth risk was attributed to APP (59.0%), while a foetal sex disparity existed (94.5% for males and 58.0% for females). Women with normal placental perfusion and a male foetus had higher credibility (e.g., higher specificities) in excluding stillbirths than those with APP and a female foetus at any given false negative rate from 1 to 10% (93.4% ~ 94.1% vs. 12.3% ~ 14.0%).

Conclusions

APP is associated with and accounts for most of the unexplained stillbirth risk. Different mechanisms exist between the sexes. The performance of screening for stillbirth may be improved by stratification according to sex and placental perfusion.
Clinical option of pemetrexed-based versus paclitaxel-based first-line chemotherapeutic regimens in combination with bevacizumab for advanced non-squamous non-small-cell lung cancer and optimal maintenance therapy: evidence from a meta-analysis of randomized control trials
Authors: Huang Le-Tian , Cao Rui , Wang Yan-Ru , Sun Li , Zhang Xiang-Yan , Guo Yi-Jia , Zhao Jian-Zhu , Zhang Shu-Ling , Jing Wei , Song Jun , Han Cheng-Bo , Ma Jietao
Published: April 2021

Background

In the era of immunotherapy, it is still unclear which is the best first-line therapy for patients with oncogenic driver negative advanced non-squamous non-small cell lung cancer (NS-NSCLC) who cannot tolerate immunotherapy, or subsequent therapy for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy. To assess the optimal choice of first-line and maintenance treatment regimens, we performed a meta-analysis of prospective randomized controlled clinical trials (RCTs) of patients with NS-NSCLC on bevacizumab combined with chemotherapy.

Methods

All eligible RCTs comparing pemetrexed-platinum with or without bevacizumab (PP ± B) and paclitaxel-carboplatin with bevacizumab (PC + B) as a first-line therapy, or comparing bevacizumab plus pemetrexed (Pem + B) and bevacizumab alone (B) as a maintenance treatment for advanced NS-NSCLC, were included after systematically searching web databases and meeting abstracts. The main research endpoints were comparisons of overall survival (OS) and progression-free survival (PFS). The other endpoints were objective response rate (ORR), 1-year PFS rate (PFSR1y) and major grade 3/4 treatment-related adverse events.

Results

Data of 3139 patients from six RCTs were incorporated into analyses. Three RCTs were included in an analysis that compared PP ± B and PC + B as a first-line therapy for advanced NS-NSCLC. Patients treated with first-line PP ± B showed similar OS and ORR, but significantly improved PFS (hazard ratio [HR], 0.88) and PFSR1y (risk ratio [RR], 0.83), as compared to patients treated with PC + B (all P < 0.05). PP ± B resulted in higher rates of grade 3/4 anemia and thrombocytopenia, but lower rates of neutropenia, febrile neutropenia, and sensory neuropathy than PC + B (all P < 0.001). The other three RCTs were included in an analysis that compared Pem + B and B as a maintenance treatment. Compared with B, Pem + B maintenance treatment resulted in significant improvements in OS (HR, 0.88), PFS (HR, 0.64), and PFSR1y (RR, 0.70), but higher rates of anemia, thrombocytopenia, and neutropenia (all P < 0.001).

Conclusion

Although the first-line PP + B regimen had longer PFS and PFSR1y than the PC + B regimen, no OS difference was observed. Addition of pemetrexed to bevacizumab as maintenance therapy significantly improved OS compared with bevacizumab maintenance alone, but led to more toxicity.
Treatment beyond progression with anti-PD-1/PD-L1 based regimens in advanced solid tumors: a systematic review
Authors: Spagnolo Francesco , Boutros Andrea , Cecchi Federica , Croce Elena , Tanda Enrica Teresa , Queirolo Paola
Published: April 2021

Background

Treatment beyond progression with immunotherapy may be appropriate in selected patients based on the potential for late responses. The aim of this systematic review was to explore the impact of treatment beyond progression in patients receiving an anti-PD-1/PD-L1 based regimen for an advanced solid tumor.

Methods

A systematic literature search was performed to identify prospective clinical trials reporting data on overall response rate by immune-related criteria and/or the number of patients treated beyond conventional criteria-defined PD and/or the number of patients achieving a clinical benefit after an initial PD with regimens including an anti-PD-1/PD-L1 agent which received the FDA approval for the treatment of an advanced solid tumor.

Results

254 (4.6%) responses after an initial RECIST-defined progressive disease were observed among 5588 patients, based on 35 trials included in our analysis reporting this information. The overall rate of patients receiving treatment beyond progressive disease was 30.2%, based on data on 5334 patients enrolled in 36 trials, and the rate of patients who achieved an unconventional response among those treated beyond progressive disease was 19.7% (based on 25 trials for a total of 853 patients).

Conclusion

The results of our systematic review support the clinical relevance of unconventional responses to anti-PD-1/PD-L1-based regimens; however, most publications provided only partial information regarding immune-related clinical activity, or did not provide any information at all, highlighting the need of a more comprehensive report of such data in trials investigating immunotherapy for the treatment of patients with advanced tumors.
The courses of objective physical activity and the association with sleepiness during a 2-week-on/2-week-off offshore shift rotation: an observational repeated-measures study
Authors: Ots P. , Riethmeister V. , Almansa J. , Bültmann U. , Brouwer S.
Published: April 2021

Background

Offshore workers are assumed to have poor health behaviours, but no studies have yet examined physical activity (PA) during a full offshore shift rotation period, including both work and at home periods. Furthermore, the relationship of PA with sleepiness, a prevalent safety hazard offshore, is not known. This study aimed to examine (1) the courses of objectively measured PA in offshore workers during pre-, offshore and post-offshore periods, and (2) the association between PA and self-reported sleepiness.

Methods

An observational repeated measures study was conducted among 36 offshore workers during a full 2-week on/2-week off offshore shift rotation. Objective PA was assessed using Daytime Activity Averages (DAA) from actigraph recordings. Sleepiness was assessed using next-morning Karolinska Sleepiness Scale (KSS) scores. The courses of PA over time were analysed with Linear Mixed Models (LMM). Parallel LMM were used to assess the longitudinal relationship between PA and sleepiness, both on a between-person and within-person level.

Results

The courses of PA were not significantly different between the pre-, offshore, and post-offshore periods. In addition, between-person trends of PA and sleepiness were not associated (p ranges between 0.08─0.99) and PA did not affect next-morning sleepiness on a within-person level (p = 0.15).

Conclusions

PA levels during the offshore working period were not different from PA levels at home. Furthermore, PA was not associated with next-morning sleepiness. Further research should focus on different levels of PA including its intensity level.
Assessment of the core and support functions of the integrated disease surveillance and response system in Zanzibar, Tanzania
Authors: Saleh Fatma , Kitau Jovin , Konradsen Flemming , Mboera Leonard E. G. , Schiøler Karin L.
Published: April 2021

Background

Disease surveillance is a cornerstone of outbreak detection and control. Evaluation of a disease surveillance system is important to ensure its performance over time. The aim of this study was to assess the performance of the core and support functions of the Zanzibar integrated disease surveillance and response (IDSR) system to determine its capacity for early detection of and response to infectious disease outbreaks.

Methods

This cross-sectional descriptive study involved 10 districts of Zanzibar and 45 public and private health facilities. A mixed-methods approach was used to collect data. This included document review, observations and interviews with surveillance personnel using a modified World Health Organization generic questionnaire for assessing national disease surveillance systems.

Results

The performance of the IDSR system in Zanzibar was suboptimal particularly with respect to early detection of epidemics. Weak laboratory capacity at all levels greatly hampered detection and confirmation of cases and outbreaks. None of the health facilities or laboratories could confirm all priority infectious diseases outlined in the Zanzibar IDSR guidelines. Data reporting was weakest at facility level, while data analysis was inadequate at all levels (facility, district and national). The performance of epidemic preparedness and response was generally unsatisfactory despite availability of rapid response teams and budget lines for epidemics in each district. The support functions (supervision, training, laboratory, communication and coordination, human resources, logistic support) were inadequate particularly at the facility level.

Conclusions

The IDSR system in Zanzibar is weak and inadequate for early detection and response to infectious disease epidemics. The performance of both core and support functions are hampered by several factors including inadequate human and material resources as well as lack of motivation for IDSR implementation within the healthcare delivery system. In the face of emerging epidemics, strengthening of the IDSR system, including allocation of adequate resources, should be a priority in order to safeguard human health and economic stability across the archipelago of Zanzibar.