bluuebunny/crossref_metadata_2025 huggingface dataset:
PTEN loss correlates with T cell exclusion across human cancers
Authors: Lin Ziying , Huang Lixia , Li Shao Li , Gu Jincui , Cui Xiaoxian , Zhou Yanbin
Published: April 2021

Background

Recent evidences had shown that loss in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was associated with immunotherapy resistance, which may be attributed to the non-T-cell-inflamed tumor microenvironment. The impact of PTEN loss on tumor microenvironment, especially regarding T cell infiltration across tumor types is not well understood.

Methods

Utilizing The Cancer Genome Atlas (TCGA) and publicly available dataset of immunotherapy, we explored the correlation of PTEN expressing level or genomic loss with tumor immune microenvironment and response to immunotherapy. We further investigated the involvement of PI3K-AKT-mTOR pathway activation, which is known to be the subsequent effect of PTEN loss, in the immune microenvironment modulation.

Results

We reveal that PTEN mRNA expression is significantly positively correlated with CD4/CD8A gene expression and T cells infiltration especially T helpers cells, central memory T cell and effector memory T cells in multiples tumor types. Genomic loss of PTEN is associated with reduced CD8+ T cells, type 1 T helper cells, and increased type 2 T helper cells, immunosuppressed genes (e.g. VEGFA) expression. Furthermore, T cell exclusive phenotype is also observed in tumor with PI3K pathway activation or genomic gain in PIK3CA or PIK3CB. PTEN loss and PI3K pathway activation correlate with immunosuppressive microenvironment, especially in terms of T cell exclusion. PTEN loss predict poor therapeutic response and worse survival outcome in patients receiving immunotherapy.

Conclusion

These data brings insight into the role of PTEN loss in T cell exclusion and immunotherapy resistance, and inspires further research on immune modulating strategy to augment immunotherapy.
Intentional internal drainage tube method for nonlocalized persistent pancreatic leakage: a case report
Authors: Furuya Kinji , Oda Tatsuya , Shimomura Osamu , Ozawa Yusuke , Iwasaki Kenichi , Miyazaki Yoshihiro , Doi Manami , Ogawa Koichi , Owada Yohei , Ohara Yusuke , Takahashi Kazuhiro , Akashi Yoshimasa , Hisakura Katsuji , Enomoto Tsuyoshi , Kim Jaejeong , Hashimoto Shinji
Published: April 2021

Background

Persistent pancreatic leakage (PL) due to disconnected pancreatic duct syndrome (DPDS) is associated with severe morbidity and mortality and it usually treated with internal drainage. However, in cases without localized fistula formation, internal drainage is challenging to perform. We report an original one-stage surgical approach for nonlocalized persistent PL, namely, the “intentional internal drainage tube method”.

Case presentation

A 49-year-old woman whose main pancreatic duct was penetrated during endoscopic retrograde cholangiopancreatography experienced severe PL. Peritoneal lavage and a second operation involving central pancreatectomy failed to relieve the symptoms, and nonlocalized PL persisted due to DPDS. Although we attempted a radical resection of the pancreatic remnants as a third strategy, the highly inflamed tissue and massive bleeding prevented the completion of the procedure. We sutured the pancreatic head margin and performed a pancreaticojejunostomy to the distal margin. Because these two cut margins could possibly be the source of the persistent PL, we created a hole at the Roux-en-Y jejunal limb, and a silicone drainage tube was inserted into the peritoneal space via this hole. Postoperatively, we continuously suctioned the intentional internal drainage tube, and the residual PL cavity gradually diminished. Even after removal of the tube, the residual PL drained internally into the jejunum through this hole.

Conclusions

We present this intentional internal drainage tube method as a novel alternative approach for the management of nonlocalized PL consequential of DPDS. Due to the simplicity and minimally invasive nature of this method, we propose this technique may also be used to treat various types of nonlocalized persistent PL or be used prophylactically for central pancreatectomy.
Surgery for craniovertebral junction pathologies: minimally invasive anterior submandibular retropharyngeal key-hole approach
Authors: Viola Árpád , Kozma István , Süvegh Dávid
Published: April 2021

Background

Our objective was to develop a new, minimally invasive surgical technique for the resolution of craniovertebral junction pathologies, which can eliminate the complications of the previous methods, like liquor-leakage, velopharyngeal insufficiency and wound-dehiscence associated with the transoral or lateral approaches.

Methods

During the first stage of the operation, three patients underwent occipito-cervical dorsal fusion, while the fourth patient received C1–C2 fusion according to Harms. C1–C2 decompressive laminectomy was performed in all four cases. Ventral C1–C2 decompression with microscope assisted minimally invasive anterior submandibular retropharyngeal key-hole approach (MIS ASR) method was performed in the second stage. The MIS ASR—similarly to the traditional anterior retropharyngeal surgery—preserves the hard and soft palates, yet can be performed through a 25 mm wide incision with the use of only one retractor.

Results

The MIS ASR approach was a success in all four cases, there were no intra- and postoperative complications. This method, compared to the transoral approach, provided on average 23% (4.56 cm2/6.05 cm2) smaller dural decompression area; nonetheless, the entire pathology could be removed in all cases. After the surgery, all patients have shown significant neurological improvement.

Conclusion

Based on the outcome of these four cases we think that the MIS ASR approach is a safe alternative to the traditional methods while improving patient safety by reducing the risk of complications.
Evaluation of hTERT, KRT7, and survivin in urine for noninvasive detection of bladder cancer using real‐time PCR
Authors: Yahyazadeh Reza , Bashash Davood , Ghaffari Parisa , Kord Saeid , Safaroghli-Azar Ava , Ghaffari Seyed H.
Published: April 2021

Background

Transitional cell carcinoma (TCC) of the bladder is the second most common genitourinary malignancy. Because of the low sensitivity of urinary cytology and the invasiveness and expense of frequent cystoscopies for the detection of low-grade superficial lesions, we aim to establish a sensitive molecular approach to detect bladder cancer noninvasively.

Methods

Voided urine samples were collected from 80 patients with bladder cancer at the time of diagnosis, in addition to 30 patients with non-bladder cancer urological diseases and 20 healthy volunteers. The level of hTERT, KRT7, and survivin (SVV) mRNAs were analyzed using a qRT-PCR assay.

Results

The optimal threshold values for hTERT, KRT7, and SVV in urine were calculated by ROC curves analysis. The overall sensitivity was 81.3%, 91.3%, and 68.8% for hTERT, KRT7, and SVV, respectively, which were significantly higher than urine cytology (22.2%, p < 0.001). A higher positive ratio was obtained using multi-marker detection in comparison to single marker detection. The combined use of markers increased the sensitivity of cytology from 22.2 to 100%. In contrast with the urine cytology method, the sensitivity of these biomarkers was not correlated with the grades and stages of the bladder tumors.

Conclusions

Our data indicate that urinary hTERT, KRT7, and SVV have superior sensitivities over cytology. The combined use of these markers offers a powerful potential assay and promising tool for a sensitive, noninvasive, and highly specific diagnostic method and follow-up of low-grade TCC of the bladder.
Alternatives to free flap surgery for maxillofacial reconstruction: focus on the submental island flap and the pectoralis major myocutaneous flap
Authors: Meier J. K. , Spoerl S. , Spanier G. , Wunschel M. , Gottsauner M. J. , Schuderer J. , Reichert T. E. , Ettl T.
Published: April 2021

Background

Microvascular tissue transfer (MTT) has been established as the gold standard in oral- and maxillofacial reconstruction. However, free flap surgery may be critical in multimorbid elderly patients and after surgery or radiotherapy, which aggravate microsurgery. This study evaluates indications and outcome of the submental island flap (SMIF) and the pectoralis major myocutaneous flap (PMMF) as alternatives to the free radial forearm flap (RFF).

Methods

This retrospective study included 134 patients who had undergone resection and reconstruction with SMIF, PMMF, or RFF at our department between 2005 and 2020. The level of comorbidity was measured with the Age-adjusted Charlson comorbidity index (ACCI). Primary outcome variables were flap success, complications, wound dehiscence, surgery duration, as well as time at the ICU and the ward (hospitalization). Chi-square tests, t-tests, and ANOVA were performed for statistics.

Results

24 SMIFs, 52 RFFs, and 58 PMMFs were included in this study. The flap types did not significantly differ in terms of flap success, complications, and healing disorders. The SMIF presented a success rate of 95.8% and was significantly more often used in elderly patients (mean age = 70.2 years; p < 0.001) with increased comorbidities than the PMMF (p < 0.01) and RFF (p < 0.001). SMIF reconstruction reduced surgery duration (p < 0.001) and time at the ICU (p = 0.009) and the ward (p < 0.001) more than PMMF and RFF reconstructions. PMMF reconstruction was successful in 91.4% of patients and was more frequently used after head and neck surgery (p < 0.001) and radiotherapy (p < 0.001) than SMIF and RFF reconstructions. Patients undergoing PMMF reconstruction more frequently required segmental jaw resection and had presented with advanced tumor stages (both p < 0.001). Nicotine and alcohol abuse was more frequent in the RFF and PMMF groups (both p < 0.001) than in the SMIF group.

Conclusions

The pedicled SMIF represents a valuable reconstructive option for elderly patients with increased comorbidity because of the shorter duration of surgery and hospitalization. On the other hand, the PMMF serves as a solid backup solution after head and neck surgery or radiotherapy. The rates of flap success, complications, and healing disorders of both pedicled flaps are comparable to those of free flap reconstruction.
Prediction of neonatal deaths in NICUs: development and validation of machine learning models
Authors: Sheikhtaheri Abbas , Zarkesh Mohammad Reza , Moradi Raheleh , Kermani Farzaneh
Published: April 2021

Background

Prediction of neonatal deaths in NICUs is important for benchmarking and evaluating healthcare services in NICUs. Application of machine learning techniques can improve physicians’ ability to predict the neonatal deaths. The aim of this study was to present a neonatal death risk prediction model using machine learning techniques.

Methods

This study was conducted in Tehran, Iran in two phases. Initially, important risk factors in neonatal death were identified and then several machine learning models including Artificial Neural Network (ANN), decision tree (Random Forest (RF), C5.0 and CHART tree), Support Vector Machine (SVM), Bayesian Network and Ensemble models were developed. Finally, we prospectively applied these models to predict neonatal death in a NICU and followed up the neonates to compare the outcomes of these neonates with real outcomes.

Results

17 factors were considered important in neonatal mortality prediction. The highest Area Under the Curve (AUC) was achieved for the SVM and Ensemble models with 0.98. The best precision and specificity were 0.98 and 0.94, respectively for the RF model. The highest accuracy, sensitivity and F-score were achieved for the SVM model with 0.94, 0.95 and 0.96, respectively. The best performance of models in prospective evaluation was for the ANN, C5.0 and CHAID tree models.

Conclusion

Using the developed machine learning models can help physicians predict the neonatal deaths in NICUs.
Performance of health workers on neonatal resuscitation care following scaled-up quality improvement interventions in public hospitals of Nepal - a prospective observational study
Authors: Chaulagain Dipak Raj , Malqvist Mats , Brunell Olivia , Wrammert Johan , Basnet Omkar , KC Ashish
Published: April 2021

Background

High-quality resuscitation among non-crying babies immediately after birth can reduce intrapartum-related deaths and morbidity. Helping Babies Breathe program aims to improve performance on neonatal resuscitation care in resource-limited settings. Quality improvement (QI) interventions can sustain simulated neonatal resuscitation knowledge and skills and clinical performance. This study aimed to evaluate the effect of a scaled-up QI intervention package on the performance of health workers on basic neonatal resuscitation care among non-crying infants in public hospitals in Nepal.

Methods

A prospective observational cohort design was applied in four public hospitals of Nepal. Performances of health workers on basic neonatal care were analysed before and after the introduction of the QI interventions.

Results

Out of the total 32,524 births observed during the study period, 3031 newborn infants were not crying at birth. A lower proportion of non-crying infants were given additional stimulation during the intervention compared to control (aOR 0.18; 95% CI 0.13–0.26). The proportion of clearing the airway increased among non-crying infants after the introduction of QI interventions (aOR 1.23; 95% CI 1.03–1.46). The proportion of non-crying infants who were initiated on BMV was higher during the intervention period (aOR 1.28, 95% CI 1.04–1.57) compared to control. The cumulative median time to initiate ventilation during the intervention was 39.46 s less compared to the baseline.

Conclusion

QI intervention package improved health workers’ performance on the initiation of BMV, and clearing the airway. The average time to first ventilation decreased after the implementation of the package. The QI package can be scaled-up in other public hospitals in Nepal and other similar settings.
Gene network analyses unveil possible molecular basis underlying drug-induced glaucoma
Authors: Ding Ruo-Fan , Yu Qian , Liu Ke , Du Juan , Yin Hua-Jun , Ji Zhi-Liang
Published: April 2021

Background

Drug-induced glaucoma (DIG) is a kind of serious adverse drug reaction that can cause irreversible blindness. Up-to-date, the molecular mechanism of DIG largely remains unclear yet due to the medical complexity of glaucoma onset.

Methods

In this study, we conducted data mining of tremendous historical adverse drug events and genome-wide drug-regulated gene signatures to identify glaucoma-associated drugs. Upon these drugs, we carried out serial network analyses, including the weighted gene co-expression network analysis (WGCNA), to illustrate the gene interaction network underlying DIG. Furthermore, we applied pathogenic risk assessment to discover potential biomarker genes for DIG.

Results

As the results, we discovered 13 highly glaucoma-associated drugs, a glaucoma-related gene network, and 55 glaucoma-susceptible genes. These genes likely played central roles in triggering DIGs via an integrative mechanism of phototransduction dysfunction, intracellular calcium homeostasis disruption, and retinal ganglion cell death. Further pathogenic risk analysis manifested that a panel of nine genes, particularly OTOF gene, could serve as potential biomarkers for early-onset DIG prognosis.

Conclusions

This study elucidates the possible molecular basis underlying DIGs systematically for the first time. It also provides prognosis clues for early-onset glaucoma and thus assists in designing better therapeutic regimens.
Malnutrition affects cholesterol paradox in coronary artery disease: a 41,229 Chinese cohort study
Authors: Wang Bo , Liu Jin , Chen Shiqun , Ying Ming , Chen Guanzhong , Liu Liwei , Lun Zhubin , Li Huanqiang , Huang Haozhang , Li Qiang , Yu Yaren , Lin Mengfei , Wei Wen , Huang Zhidong , Yang Yongquan , Chen Jiyan , Tan Ning , Liu Yong
Published: April 2021

Background

Several studies have found that a low baseline low -density lipoprotein cholesterol (LDL-C) concentration was associated with poor prognosis in patients with acute coronary syndrome (ACS), which is called the “cholesterol paradox”. Low LDL-C concentration may reflect underlying malnutrition, which was strongly associated with increased mortality. The aim of this study was to investigate the cholesterol paradox in patients with CAD and the effects of malnutrition.

Method

A total of 41,229 CAD patients admitted to Guangdong Provincial People’s Hospital in China were included in this study from January 2007 to December 2018 and divided into two groups (LDL-C < 1.8 mmol/L, n = 4863; LDL-C ≥ 1.8 mmol/L, n = 36,366). The Kaplan-Meier method and Cox regression analyses were used to assess the association between LDL-C levels and long-term all-cause mortality and the effect of malnutrition.

Result

In this real-world cohort (mean age 62.9 years; 74.9% male), there were 5257 cases of all-cause death during a median follow-up of 5.20 years [interquartile range (IQR): 3.05–7.78 years]. Kaplan–Meier analysis showed that low LDL-C levels were associated with a worse prognosis. After adjusting for baseline confounders (e.g., age, sex and comorbidities, etc.), multivariate Cox regression analysis revealed that a low LDL-C level (< 1.8 mmol/L) was not significantly associated with all-cause mortality (adjusted HR, 1.04; 95% CI, 0.96–1.24). After adjustment for nutritional status, the risk of all-cause mortality in patients with low LDL-C levels decreased (adjusted HR, 0.90; 95% CI, 0.83–0.98). In the final multivariate Cox model, a low LDL-C level was related to better prognosis (adjusted HR, 0.91; 95% CI, 0.84–0.99).

Conclusion

This study demonstrated that the cholesterol paradox existed in CAD patients but disappeared after accounting for the effects of malnutrition.
Serum complement proteomics reveal biomarkers for hypertension disorder of pregnancy and the potential role of Clusterin
Authors: Zeng Shanshui , Han Mengru , Jiang Min , Liu Fei , Hu Yanwei , Long Yan , Zhu Chunyan , Zeng Fangling , Gan Qiangsheng , Ye Weitao , Fu Wenjin , Yang Hongling
Published: April 2021

Introduction

Hypertension disorder of pregnancy (HDP) is one of the leading causes of maternal and foetal illness. The aim of the current study was to identify and verify novel serum markers for HDP.

Methods

A label-free LC-MS/MS method was used to establish the serum proteomic profiles of 12 pre-HDP (before clinical diagnosis of HDP) pregnancies and verify prioritized candidates in the verification set of 48 pre-HDP pregnancies. These biomarkers were revalidated by ELISA in an independent cohort of 88 pre-HDP pregnancies. Subsequently, the candidate biomarkers were histologically analysed by immunohistochemistry, and function was evaluated in TEV-1 cells.

Results

We identified 33 proteins with significantly increased abundance and 14 with decreased abundance (peptide FDR ≤ 1%, P < 0.05). Complement was one of the top enriched components in the pre-HDP group compared with the control group. Three complement factors (CLU, CFHR5, and CRP) were significantly increased in the three sets, of which CLU was a critical factor for the development of HDP (OR = 1.22, P < 0.001). When these three factors and body weight were combined, the AUC was 0.74, with a sensitivity of 0.67 and specificity of 0.68 for HDP prediction compared with normal pregnancy. In addition, inflammation-induced CLU could inhibit the invasion of TEV-1 cells.

Conclusions

Complement proteins may play an essential role in the occurrence of HDP by acting on trophoblast cells. CLU may be a high-risk factor for HDP, and the models combining candidates show reasonable screening efficiency of HDP in the first half of pregnancy.
Nonnegligible causes of symptoms of acute lower extremities——3 cases of May-Thurner syndrome with deep vein thrombosis
Authors: Sun Yi , Song Shenghan
Published: April 2021

Background

May-Thurner syndrome is a kind of disease caused by the compression of the left common iliac vein. It is one of the causes of incomplete venous valves and superficial varicose veins in lower limbs, and is also a potential factor of acute deep vein thrombosis (DVT).

Method

Here 3 cases are diagnosed as May-Thurner syndrome at different ages.

Case presentations

1. A 35-year-old female patient was hospitalized with swelling of the left lower limb for 1 week. Computed tomography (CT) showed compression of the left common iliac vein with thrombosis. May-Thurner syndrome was diagnosed and catheter-directed thrombolysis was performed. 2. A 37-year-old male patient came to our hospital due to sudden swelling of the right lower extremity and pain for 3 days. Computed tomography showed compression of the left common iliac vein and deep venous thrombosis (DVT) of the right iliac vein. May-Thurner syndrome was diagnosed. The patient was performed with inferior vena cava (IVC) filter implantation, catheter-directed thrombolysis and balloon angioplasty for right iliac vein. And the patient recovered well; 3. A 55-year-old female patient came to our hospital with swelling and discomfort in the left lower extremity for 3 days. Computed tomography showed stenosis of the left common iliac vein with deep vein thrombosis. May-Thurner syndrome was diagnosed, balloon dilation and stent implantation were performed. During 3 years of follow-up, there was no swelling or new thrombosis in her lower limbs.

Conclusion

When encountering unexplained deep vein thrombosis, iliac vein compression syndrome should be considered and treated in time to prevent the recurrence of thrombosis. Catheter-directed thrombolysis can relieve symptoms and stenting placement is the optimal way to relieve stenosis, supplemented by long-term anticoagulation therapy and graduated compression stockings.
Exploring women’s childbirth experiences and perceptions of delivery care in peri-urban settings in Nairobi, Kenya
Authors: Oluoch-Aridi Jackline , Afulani Patience. A. , Guzman Danice. B. , Makanga Cindy , Miller-Graff Laura
Published: April 2021

Background

Kenya continues to have a high maternal mortality rate that is showing slow progress in improving. Peri-urban settings in Kenya have been reported to exhibit higher rates of maternal death during labor and childbirth as compared to the general Kenyan population. Although research indicates that women in Kenya have increased access to facility-based birth in recent years, a small percentage still give birth outside of the health facility due to access challenges and poor maternal health service quality. Most studies assessing facility-based births have focused on the sociodemographic determinants of birthing location. Few studies have assessed women’s user experiences and perceptions of quality of care during childbirth. Understanding women’s experiences can provide different stakeholders with strategies to structure the provision of maternity care to be person-centered and to contribute to improvements in women’s satisfaction with health services and maternal health outcomes.

Methods

A qualitative study was conducted, whereby 70 women from the peri-urban area of Embakasi in the East side of Nairobi City in Kenya were interviewed. Respondents were aged 18 to 49 years and had delivered in a health facility in the preceding six weeks. We conducted in-depth interviews with women who gave birth at both public and private health facilities. The interviews were recorded, transcribed, and translated for analysis. Braune and Clarke’s guidelines for thematic analysis were used to generate themes from the interview data.

Results

Four main themes emerged from the analysis. Women had positive experiences when care was person-centered—i.e. responsive, dignified, supportive, and with respectful communication. They had negative experiences when they were mistreated, which was manifested as non-responsive care (including poor reception and long wait times), non-dignified care (including verbal and physical abuse lack of privacy and confidentiality), lack of respectful communication, and lack of supportive care (including being denied companions, neglect and abandonment, and poor facility environment).

Conclusion

To sustain the gains in increased access to facility-based births, there is a need to improve person-centered care to ensure women have positive facility-based childbirth experiences.
An examination of the barriers to and benefits from collaborative couple contraceptive use in Rwanda
Authors: Schwandt Hilary , Boulware Angel , Corey Julia , Herrera Ana , Hudler Ethan , Imbabazi Claudette , King Ilia , Linus Jessica , Manzi Innocent , Merritt Madelyn , Mezier Lyn , Miller Abigail , Morris Haley , Musemakweli Dieudonne , Musekura Uwase , Mutuyimana Divine , Ntakarutimana Chimene , Patel Nirali , Scanteianu Adriana , Shemeza Biganette-Evidente , Stapleton Madi , Sterling-Donaldson Gi’anna , Umutoni Chantal , Uwera Lyse , Zeiler Madeleine , Feinberg Seth
Published: April 2021

Background

Supportive male involvement is strongly correlated with contraceptive use. In Rwanda, where the contraceptive prevalence rate among married women increased from 17 to 52% from 2005 to 2010, and stagnated at 53% in 2015, understanding the role of male partners in collaborative couple contraceptive use can help inform programs designed to further increase the use of contraception in Rwanda.

Methods

This study utilized qualitative methods in 2018, specifically 32 in-depth interviewers with mostly current users of modern contraceptive methods and eight focus group discussions with family planning providers—both family planning nurses and community health workers (CHWs). Respondents were from Musanze and Nyamasheke Districts, the districts with the highest and lowest modern contraceptive use, respectively, to explore the role of couple collaboration in family planning use in Rwanda. Data were analyzed using the thematic content approach in Atlas.ti (8).

Results

Findings demonstrate that some men are opposed to use of male methods of contraception, and some are opposed to any contraceptive use, which can lead to covert use. Women and providers prefer collaborative couple contraceptive use—as a result, providers advocate for and encourage male partner participation in contraceptive use. Women are most often burdened with seeking out information, initiating discussions, and sharing information discovered about contraceptive use with partners. Decision-making about contraceptive use, once discussed, can be collaborative and motivated by financial considerations. When couple contraceptive use is collaborative, benefits range from marital harmony to husband’s support of sustained use through reminders about appointments, joint counseling, and support in managing side effects.

Conclusion

Family planning providers at the community and clinic levels encourage collaborative contraceptive use among couples and some Rwandan couples communicate well about family planning use. Despite the positives, women are expected to source family planning information, share that information with their male partners, seek out family planning services, and use family planning. If more Rwandan male partners accepted use, used male methods of contraception, and participated even more in the work it takes to use family planning, the potential for sustained, and even enhanced, contraceptive use in Rwanda could be realized.
Kawasaki disease recurrence in the COVID-19 era: a systematic review of the literature
Authors: Medaglia Alice Annalisa , Siracusa Lucia , Gioè Claudia , Giordano Salvatore , Cascio Antonio , Colomba Claudia
Published: April 2021

Kawasaki disease (KD) is a vasculitis of unknown origin of small and medium caliber blood vessels, especially involving coronary arteries and is the leading cause of acquired heart disease in childhood in developed countries. Although rarely, it can recur: most recurrences occur within 2 years of the initial episode. No data are available on incidence of recurrent KD in Europe and multiple recurrences are rarely seen. We reviewed the medical literature on Kawasaki disease recurrence and reported a new case of Kawasaki disease recurrence in a child with SARS-CoV-2 infection. We believe that in our case SARS Cov2 acted as a trigger capable to determine, in a genetically susceptible individual, a second recurrence of the disease. In the Covid-19 era we affirm the importance for Kawasaki disease to be tested for SARS Cov2 infection.
Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study
Authors: Bhatraju Pavan K. , Morrell Eric D. , Zelnick Leila , Sathe Neha A. , Chai Xin-Ya , Sakr Sana S. , Sahi Sharon K. , Sader Anthony , Lum Dawn M. , Liu Ted , Koetje Neall , Garay Ashley , Barnes Elizabeth , Lawson Jonathan , Cromer Gail , Bray Mary K. , Pipavath Sudhakar , Kestenbaum Bryan R. , Liles W. Conrad , Fink Susan L. , West T. Eoin , Evans Laura , Mikacenic Carmen , Wurfel Mark M.
Published: April 2021

Background

Analyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Our objective was to evaluate host endothelial, epithelial and inflammatory biomarkers in COVID-19.

Methods

We prospectively enrolled 171 ICU patients, including 78 (46%) patients positive and 93 (54%) negative for SARS-CoV-2 infection from April to September, 2020. We compared 22 plasma biomarkers in blood collected within 24 h and 3 days after ICU admission.

Results

In critically ill COVID-19 and non-COVID-19 patients, the most common ICU admission diagnoses were respiratory failure or pneumonia, followed by sepsis and other diagnoses. Similar proportions of patients in both groups received invasive mechanical ventilation at the time of study enrollment. COVID-19 and non-COVID-19 patients had similar rates of acute respiratory distress syndrome, severe acute kidney injury, and in-hospital mortality. While concentrations of interleukin 6 and 8 were not different between groups, markers of epithelial cell injury (soluble receptor for advanced glycation end products, sRAGE) and acute phase proteins (serum amyloid A, SAA) were significantly higher in COVID-19 compared to non-COVID-19, adjusting for demographics and APACHE III scores. In contrast, angiopoietin 2:1 (Ang-2:1 ratio) and soluble tumor necrosis factor receptor 1 (sTNFR-1), markers of endothelial dysfunction and inflammation, were significantly lower in COVID-19 (p < 0.002). Ang-2:1 ratio and SAA were associated with mortality only in non-COVID-19 patients.

Conclusions

These studies demonstrate that, unlike other well-studied causes of critical illness, endothelial dysfunction may not be characteristic of severe COVID-19 early after ICU admission. Pathways resulting in elaboration of acute phase proteins and inducing epithelial cell injury may be promising targets for therapeutics in COVID-19.
A virtual reality-based intervention for surgical patients: study protocol of a randomized controlled trial
Authors: Georgescu Raluca Diana , Dobrean Anca , Silaghi Cristina Alina , Silaghi Horatiu
Published: April 2021

Background

Pain after surgery is normal, and treatments, including both pharmacological and psychological components, are fundamental for proper postoperative care. While several trials have investigated the analgesic effect of traditional non-pharmacological treatments, such as cognitive behavior therapies, the newer ways of delivering psychological interventions for pain after surgery are scarcely investigated. The aim of this randomized controlled trial (RCT) is to determine if delivering the psychological content through virtual reality (VR) along with the standard pharmacological treatment return better pain relief outcomes than standard care in adult patients following surgery.

Methods

This is a protocol of a parallel RCT conducted in one community hospital. In order to test the efficacy of VR environments for reducing pain intensity, in the following day after surgery, adults (18 to 65 years) will be randomly assigned to either (1) standard treatment after surgery (control group) or (2) VR based intervention along with standard treatment. It is intended that a minimum of 30 patients be recruited in each group. For estimating the intensity of pain, both self-report and physiological measures will be used. Repeated measures of pain outcomes will be taken before and after the intervention. Moreover, for allowing an in-depth investigation of the effect of VR environments, the primary outcome will be complemented with measures of the adverse effects, level of immersion, and level of presence in the VR environment.
Molecular mechanism underlying the effect of maleic hydrazide treatment on starch accumulation in S. polyrrhiza 7498 fronds
Authors: Zhu Yerong , Li Xiaoxue , Gao Xuan , Sun Jiqi , Ji Xiaoyuan , Feng Guodong , Shen Guangshuang , Xiang Beibei , Wang Yong
Published: April 2021

Background

Duckweed is considered a promising feedstock for bioethanol production due to its high biomass and starch production. The starch content can be promoted by plant growth regulators after the vegetative reproduction being inhibited. Maleic hydrazide (MH) has been reported to inhibit plant growth, meantime to increase biomass and starch content in some plants. However, the molecular explanation on the mechanism of MH action is still unclear.

Results

To know the effect and action mode of MH on the growth and starch accumulation in Spirodela polyrrhiza 7498, the plants were treated with different concentrations of MH. Our results showed a substantial inhibition of the growth in both fronds and roots, and increase in starch contents of plants after MH treatment. And with 75 µg/mL MH treatment and on the 8th day of the experiment, starch content was the highest, about 40 mg/g fresh weight, which is about 20-fold higher than the control. The I2-KI staining and TEM results confirmed that 75 µg/mL MH-treated fronds possessed more starch and big starch granules than that of the control. No significant difference for both in the photosynthetic pigment content and the chlorophyll fluorescence parameters of PII was found. Differentially expressed transcripts were analyzed in S. polyrrhiza 7498 after 75 µg/mL MH treatment. The results showed that the expression of some genes related to auxin response reaction was down-regulated; while, expression of some genes involved in carbon fixation, C4 pathway of photosynthesis, starch biosynthesis and ABA signal transduction pathway was up-regulated.

Conclusion

The results provide novel insights into the underlying mechanisms of growth inhibition and starch accumulation by MH treatment, and provide a selective way for the improvement of starch production in duckweed.
Differential expression of starch and sucrose metabolic genes linked to varying biomass yield in Miscanthus hybrids
Authors: De Vega Jose J. , Peel Ned , Purdy Sarah J. , Hawkins Sarah , Donnison Lain , Dyer Sarah , Farrar Kerrie
Published: April 2021

Background

Miscanthus is a commercial lignocellulosic biomass crop owing to its high biomass productivity and low chemical input requirements. Within an interspecific Miscanthus cross, progeny with high biomass yield were shown to have low concentrations of starch and sucrose but high concentrations of fructose. We performed a transcriptional RNA-seq analysis between selected Miscanthus hybrids with contrasting values for these phenotypes to clarify how these phenotypes are genetically controlled.

Results

We observed that genes directly involved in the synthesis and degradation of starch and sucrose were down-regulated in high-yielding Miscanthus hybrids. At the same time, glycolysis and export of triose phosphates were up-regulated in high-yielding Miscanthus hybrids. These differentially expressed genes and biological functions were regulated by a well-connected network of less than 25 co-regulated transcription factors.

Conclusions

Our results evidence a direct relationship between high expression of essential enzymatic genes in the starch and sucrose pathways and co-expression with their transcriptional regulators, with high starch concentrations and lower biomass production. The strong interconnectivity between gene expression and regulators, chemotype and agronomic traits opens the door to use the expression of well-characterised genes associated with carbohydrate metabolism, particularly in the starch and sucrose pathway, for the early selection of high biomass-yielding genotypes from large Miscanthus populations.
Estimates of the population size and dispersal range of Anopheles arabiensis in Northern KwaZulu-Natal, South Africa: implications for a planned pilot programme to release sterile male mosquitoes
Authors: Kaiser Maria L. , Wood Oliver R. , Damiens David , Brooke Basil D. , Koekemoer Lizette L. , Munhenga Givemore
Published: April 2021

Background

Anopheles arabiensisis a major malaria vector, recently implicated as contributing to ongoing residual malaria transmission in South Africa, which feeds and rests both indoors and outdoors. This species is, therefore, not effectively targeted using core malaria vector control interventions alone. Additionally, increasing resistance to available insecticides necessitates investigations into complementary non-insecticide-based vector control methods for outdoor-resting mosquitoes. The feasibility of the sterile insect technique (SIT) as a complementary vector control intervention is being investigated in South Africa. Successful implementation of an SIT programme largely depends on inundating a target insect population with sterilized laboratory-bred males. Therefore, knowledge of the native population size and dispersal ability of released sterile laboratory-reared males is critical. In this study, we estimated the maleAn. arabiensispopulation size and the dispersal of released males in an area targeted for a pilot sterile male release programme.

Methods

Three separate releases were performed within a 2-year period. Approximately 5000–15,000 laboratory-reared maleAn. arabiensis(KWAG) were produced and marked for mark–release–recapture experiments. To recapture released mosquitoes, cloth tubes were deployed in widening concentric circles. The average dispersal distance of released males was calculated and the wild maleAn. arabiensispopulation size was estimated using two Lincoln index formulae. The natural population was sampled concurrently andAnophelesspecies diversity examined.

Results

TheAnopheles gambiaecomplex andAn. funestusgroup species made up the majority of wild collections along with other anophelines. TheAn. arabiensispopulation size was estimated to be between 550 and 9500 males per hectare depending on time of year, weather conditions and method used. Average dispersal distance of marked males ranged from 58 to 86 m. Marked males were found in swarms with wild males, indicating that laboratory-reared males are able to locate and participate in mating swarms.

Conclusions

It was logistically feasible to conduct mark–release–recapture studies at the current scale. The population size estimates obtained may provide a guideline for the initial number of males to use for a pending SIT pilot trial. It is promising for future SIT trials that laboratory-reared marked males participated in natural swarms, appearing at the right place at the right time.

Graphical Abstract
Rickettsiae in red fox (Vulpes vulpes), marbled polecat (Vormela peregusna) and their ticks in northwestern China
Authors: Liu Gang , Zhao Shanshan , Tan Wenbo , Hornok Sándor , Yuan Wumei , Mi Ligu , Wang Suwen , Liu Zhiqiang , Zhang Yanyan , Hazihan Wurelihazi , Gu Xinli , Wang Yuanzhi
Published: April 2021

Background

Previously, twelveRickettsiaspecies were identified in ticks, fleas, sheep keds (Melophagus ovinus), bats (Pipistrellus pipistrellus) and a tick-bitten patient in the Xinjiang Uygur Autonomous Region (XUAR) in northwestern China. Here we aimed to molecularly detect rickettsial agents in red fox (Vulpes vulpes), marbled polecat (Vormela peregusna) and their ticks.

Methods

During 2018–2019, 12 red foxes, one marbled polecat and their ticks were sampled in two counties and a city of the XUAR. The heart, liver, spleen, lung and kidney of these 13 carnivores were dissected, followed by DNA extraction. Hard ticks were identified both morphologically and molecularly. All samples were examined for the presence of rickettsiae by amplifying four genetic markers (17-kDa, gltA, ompA, sca1).

Results

A total of 26 adult ticks and 28 nymphs (38Ixodes canisuga, nineIxodes kaiseri, sixHaemaphysalis erinaceiand oneDermacentor marginatus) were collected from red foxes, and fourHa. erinaceiticks were removed from the marbled polecat. Analysis of cytochromecoxidase subunit I (COI) gene sequences indicated that 2–32 nucleotides differed betweenI. canisuga,I. kaiseriandHa. erinaceifrom northwestern China and Europe.Rickettsia raoultiiwas detected in three red foxes,CandidatusRickettsia barbariae in a red fox,Rickettsia sibiricain a red fox and a marbled polecat, andR. raoultiiin two tick species (I. canisugaandD.marginatus).

Conclusions

To the best of our knowledge,I. canisugaandI. kaiserihave not been previously reported from red foxes in China. The DNA ofR. sibiricaandR. raoultiiwas detected for the first time in the organs of red foxes, andR. sibiricain the organs of a marbled polecat. This is also the first molecular evidence for the presence ofR. raoultiiinI. canisuga. Our findings expand the range of tick-borne pathogens in wildlife species and associated ticks in China.

Graphical Abstract
A community-driven resource for genomic epidemiology and antimicrobial resistance prediction of Neisseria gonorrhoeae at Pathogenwatch
Authors: Sánchez-Busó Leonor , Yeats Corin A. , Taylor Benjamin , Goater Richard J. , Underwood Anthony , Abudahab Khalil , Argimón Silvia , Ma Kevin C. , Mortimer Tatum D. , Golparian Daniel , Cole Michelle J. , Grad Yonatan H. , Martin Irene , Raphael Brian H. , Shafer William M. , Town Katy , Wi Teodora , Harris Simon R. , Unemo Magnus , Aanensen David M.
Published: April 2021

Background

Antimicrobial-resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last-line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones and transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community-driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance.

Methods

Here we present a public health-focussed scheme for genomic epidemiology of N. gonorrhoeae at Pathogenwatch (https://pathogen.watch/ngonorrhoeae). An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to inform on the utility of current and future analytics in the platform. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants linked to a genotypic prediction of resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization.

Results

AMR prediction from genome data revealed specificity values over 99% for azithromycin, ciprofloxacin and ceftriaxone and sensitivity values around 99% for benzylpenicillin and tetracycline. A case study using the Pathogenwatch collection of N. gonorrhoeae public genomes showed the global expansion of an azithromycin-resistant lineage carrying a mosaic mtr over at least the last 10 years, emphasising the power of Pathogenwatch to explore and evaluate genomic epidemiology questions of public health concern.

Conclusions

The N. gonorrhoeae scheme in Pathogenwatch provides customised bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower-resourced settings with internet connection but limited computational infrastructure. The advisory group will assess and identify ongoing public health needs in the field of gonorrhoea, particularly regarding gonococcal AMR, in order to further enhance utility with modified or new analytic methods.
Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies
Authors: Lau Billy T. , Pavlichin Dmitri , Hooker Anna C. , Almeda Alison , Shin Giwon , Chen Jiamin , Sahoo Malaya K. , Huang Chun Hong , Pinsky Benjamin A. , Lee Ho Joon , Ji Hanlee P.
Published: April 2021

Background

The genome of SARS-CoV-2 is susceptible to mutations during viral replication due to the errors generated by RNA-dependent RNA polymerases. These mutations enable the SARS-CoV-2 to evolve into new strains. Viral quasispecies emerge from de novo mutations that occur in individual patients. In combination, these sets of viral mutations provide distinct genetic fingerprints that reveal the patterns of transmission and have utility in contact tracing.

Methods

Leveraging thousands of sequenced SARS-CoV-2 genomes, we performed a viral pangenome analysis to identify conserved genomic sequences. We used a rapid and highly efficient computational approach that relies on k-mers, short tracts of sequence, instead of conventional sequence alignment. Using this method, we annotated viral mutation signatures that were associated with specific strains. Based on these highly conserved viral sequences, we developed a rapid and highly scalable targeted sequencing assay to identify mutations, detect quasispecies variants, and identify mutation signatures from patients. These results were compared to the pangenome genetic fingerprints.

Results

We built a k-mer index for thousands of SARS-CoV-2 genomes and identified conserved genomics regions and landscape of mutations across thousands of virus genomes. We delineated mutation profiles spanning common genetic fingerprints (the combination of mutations in a viral assembly) and a combination of mutations that appear in only a small number of patients. We developed a targeted sequencing assay by selecting primers from the conserved viral genome regions to flank frequent mutations. Using a cohort of 100 SARS-CoV-2 clinical samples, we identified genetic fingerprints consisting of strain-specific mutations seen across populations and de novo quasispecies mutations localized to individual infections. We compared the mutation profiles of viral samples undergoing analysis with the features of the pangenome.

Conclusions

We conducted an analysis for viral mutation profiles that provide the basis of genetic fingerprints. Our study linked pangenome analysis with targeted deep sequenced SARS-CoV-2 clinical samples. We identified quasispecies mutations occurring within individual patients and determined their general prevalence when compared to over 70,000 other strains. Analysis of these genetic fingerprints may provide a way of conducting molecular contact tracing.