bluuebunny/crossref_metadata_2025 huggingface dataset:
Placental pathology in a pregnant woman with severe COVID-19 and successful ECMO treatment: a case report
Authors: Rosner-Tenerowicz Anna , Fuchs Tomasz , Zimmer-Stelmach Aleksandra , Pomorski Michał , Trzeszcz Martyna , Zwierzchowski Jacek , Zimmer Mariusz
Published: November 2021

Background

Infection with SARS-CoV-2 during pregnancy can lead to a severe condition in the patient, which is challenging for obstetricians and anaesthesiologists. Upon severe COVID-19 and a lack of improvement after multidrug therapy and mechanical ventilation, extracorporeal membrane oxygenation (ECMO) is introduced as the last option. Such treatment is critical in women with very preterm pregnancy when each additional day of the intrauterine stay is vital for the survival of the newborn.

Case presentation

We report a case of a 38-year-old woman at 27 weeks of gestation treated with multidrug therapy and ECMO. The woman was admitted to the intensive care unit (ICU) with increasing fever, cough and dyspnoea. The course of the pregnancy was uncomplicated. She was otherwise healthy. At admission, she presented with severe dyspnoea, with oxygen saturation (SpO2) of 95% on passive oxygenation, heart rate of 145/min, and blood pressure of 145/90. After confirmation of SARS-CoV-2 infection, she received steroids, remdesivir and convalescent plasma therapy. The foetus was in good condition. No signs of an intrauterine infection were visible. Due to tachypnea of 40/min and SpO2 of 90%, the woman was intubated and mechanically ventilated. Due to circulatory failure, the prothrombotic activity of the coagulation system, further saturation worsening, and poor control of sedation, she was qualified for veno-venous ECMO. An elective caesarean section was performed at 29 weeks on ECMO treatment in the ICU. A preterm female newborn was delivered with an Apgar score of 7 and a birth weight of 1440 g. The newborn had no laboratory or clinical evidence of COVID-19. The placenta showed the following pathological changes: large subchorionic haematoma, maternal vascular malperfusion, marginal cord insertion, and chorangioma.

Conclusions

This case presents the successful use of ECMO in a pregnant woman with acute respiratory distress syndrome in the course of severe COVID-19. Further research is required to explain the aetiology of placental disorders (e.g., maternal vascular malperfusion lesions or thrombotic influence of COVID-19). ECMO treatment in pregnant women remains challenging; thus, it should be used with caution. Long-term assessment may help to evaluate the safety of the ECMO procedure in pregnant women.
The development and validation of the psychological capital questionnaire for patients with Cancer the psychological capital questionnaire
Authors: Cui Chun Ying , Wang Yu , Zhang Ying , Chen Siqi , Jiang Nan , Wang Lie
Published: November 2021

Background

Studies increasingly show that positive psychological constructs affect the mental health of cancer patients. However, most scales that measure hope, resilience, optimism and self-efficacy have been developed based on general populations. The aim of our study was to develop a psychological capital (PsyCap) questionnaire for patients with cancer (PCQ-C) to gauge their mental state more accurately.

Methods

The items for the scale were selected by comprehensive literature review and semi-structured interviews, and the relevant terms were screened by an expert panel. A pilot study was then conducted on 202 patients to reduce the item pool, and the reliability and validity of the scale were evaluated using 500 completed questionnaires. The test-retest reliability was then assessed using a subsample of 100 patients. Finally, the completed questionnaires of 229 patients with breast cancer were used to assess the criterion validity of the PCQ-C, including measures of depression and anxiety.

Results

Item reduction and exploratory factory analysis resulted in 24 items for self-efficacy, hope, resilience and optimism, accounting for 56.72% of the variance. The Cronbach’s alpha for the scale was 0.886, and the test-retest reliability was 0.825. PsyCap showed a significant negative correlation with both depression (r = − 0.631,P < 0.01) and anxiety (r = − 0.601,P < 0.01).

Conclusion

The PCQ-C can objectively evaluate PsyCap in cancer patients and exhibits good psychometric properties.
Causes of poor eye contact in infants: a population-based study
Authors: Levinsen Mette , Børresen Malene Landbo , Roos Laura , Grønskov Karen , Kessel Line
Published: November 2021

Background

Establishing eye contact between infants and parents is important for early parent-child bonding and lack of eye contact may be a sign of severe underlying disease. The aim of the study was to evaluate the causes of poor or lacking eye contact in infants.

Methods

Cross-sectional study reviewing all referrals of infants ≤1 year of age from January 1rst, 2016 to December 31rst, 2018. Medical information was retrieved from patient files covering pregnancy, birth, diagnostic work-up and ocular parameters such as refraction, visual acuity and structural findings.

Results

We identified 99 infants with poor or lacking eye contact. The relative frequency of causes was neurologic disease 36.4% (36/99), delayed visual maturation 24.2% (24/99), ocular disease 21.2% (21/99) and idiopathic infantile nystagmus 4.0% (4/99). Fourteen infants had a visual function within age-related norms at first examination despite poor eye contact at the time of referral. Of the infants with available data, 18/27 (33.3%) with neurologic cause, 15/23 (65.2%) with delayed visual maturation and 9/21 (42.9%) with ocular cause had visual acuity within the age-related norm at latest follow-up (0-41 months). In 23 infants, a genetic cause was found.

Conclusion

Poor eye contact in infants may be a sign of severe underlying disease, such as neurological or ocular disease. Close collaboration between pediatric ophthalmologists and neuro-pediatricians are warranted in the management of these infants.
Effectiveness of mobile application on changing weight, healthy eating habits, and quality of life in children and adolescents with obesity: a randomized controlled trial
Authors: Likhitweerawong Narueporn , Boonchooduang Nonglak , Kittisakmontri Kulnipa , Chonchaiya Weerasak , Louthrenoo Orawan
Published: November 2021

Background

A technology-based intervention, such as a mobile application, was a growing interest and potentially effective modality for treating obesity. The study aimed to evaluate the effectiveness of the OBEST, a new mobile/tablet-based application in reducing weight and encouraging healthy eating behaviors and quality of life in children with obesity. The application could assist healthcare professionals to treat children and adolescents with obesity.

Methods

A randomized controlled trial was conducted in the hospital and school settings in Chiang Mai, Thailand. Seventy-seven children and adolescents with obesity were randomized into two groups; one received standard care combined with the OBEST application, and the other received only standard care. The outcomes were changes in weight, healthy eating behaviors, and quality of life assessed by the Pediatric Quality of Life Inventory (PedsQL) from baseline to six-month follow-up between the two groups.

Results

The results showed that the intervention group reduced more body mass index (BMI) and had a higher number of participants engaging in healthy eating behaviors than the standard care group but did not reach a statistically significant level, except for less frequent consumption of fast food. The participants in the intervention group had 4.5 times higher odds of decreased engaging in fast-food consumption than the standard care group at 6 months follow-up (odds ratio, 4.5 [95% CI, 1.41 to 14.35]). There were no statistically significant changes in PedsQL scores over 6 months in between groups.

Conclusions

The current study was unable to detect a significant effect of the OBEST application as an adjunct tool to the standard treatment on reducing weight in obese children and adolescents. However, the mobile application might help to increase engaging in healthy eating behaviors. Further studies with a larger sample are needed to confirm our findings.

Trial registration

The trial was retrospectively registered at the Thai Clinical Trials Registry (trial registration number: TCTR20200604008, on June 4, 2020).
Airway injury and pneumomediastinum associated with less invasive surfactant administration in a premature neonate: a case report
Authors: Altamimi Talal , Read Brooke , da Silva Orlando , Bhattacharya Soume
Published: November 2021

Background

The use of less invasive surfactant administration (LISA)/minimally invasive surfactant therapy (MIST) has increased due to its potential advantage over traditional surfactant delivery methods through an endotracheal tube. Known complications for this procedure include failure of the first attempt at insertion, desaturation, and bradycardia. To the best of our knowledge, this is the first reported case of pneumomediastinum and subcutaneous emphysema following LISA.

Case presentation

A preterm newborn born at 27 weeks of gestation presented with respiratory distress syndrome requiring surfactant replacement. LISA using the Hobart method was completed. There was a report of procedural difficulty related to increased resistance to insertion of the 16G angiocath. The newborn was subsequently noted to have subcutaneous emphysema over the anterior aspect of the neck and substantial pneumomediastinum on radiological assessment. Associated complications included hypotension requiring inotropic support. The newborn was successfully managed conservatively, with complete resolution of the air leak.

Conclusions

Upper airway injury leading to air leak syndrome is a rare complication of the Hobart method for LISA. Awareness of such procedural complications is important as the use of the LISA method increases.
“Mapping suicide prevention initiatives targeting Indigenous Sámi in Nordic countries”
Authors: Stoor Jon Petter A. , Eriksen Heidi A. , Silviken Anne C.
Published: November 2021

Background

Suicide is a major public health issue among Indigenous Sámi in Nordic countries, and efforts to prevent suicide in the Sámi context are increasing. However, there is no literature on suicide prevention initiatives among Sámi. The aim of the study was to map suicide prevention initiatives targeting Sámi in Norway, Sweden, and Finland during 2005–2019.

Method

Initiatives were identified and described through utilizing networks among stakeholders in the field of suicide prevention among Sámi, acquiring documentation of initiatives and utilizing the authors first-hand experiences. The described initiatives were analyzed inspired by the “What is the problem represented to be?” (WPR)-approach.

Results

Seventeen initiatives targeting Sámi were identified during 2005–2019, including nine in Sweden, five in Norway, one in Finland and two international initiatives. Analysis with the WPR-approach yielded 40 problematizations regarding how to prevent suicide among Sámi, pertaining to shortcomings on individual (5), relational (15), community/cultural (3), societal (14) and health systems levels (3). All initiatives were adapted to the Sámi context, varying from tailor-made, culture-specific approaches to targeting Sámi with universal approaches. The most common approaches were the gatekeeper and mental health literacy training programs. The initiatives generally lacked thorough evaluation components.

Conclusion

We argue that the dominant rationales for suicide prevention were addressing shortcomings on individual and relational levels, and raising awareness in the general public. This threatens obscuring other, critical, approaches, such as broadening perspectives in prevention planning, improving health systems for Sámi, and promoting cultural empowerment among Sámi. Nevertheless, the study confirms considerable efforts have been invested into suicide prevention among Sámi during the last 15 years, and future initiatives might include a broader set of prevention rationales. To improve evaluation and identify the most promising practices, increased support regarding development of plans and implementation of evaluation components is needed.
Early signs of pneumoconiosis in a dental technician in Italy: a case report
Authors: Tiraboschi Mara Maria , Sala Emma , Ferroni Matteo , Tironi Andrea , Borghesi Andrea , Gilberti Maria Enrica , Ceruti Paolo , Sansone Emanuele , De Palma Giuseppe
Published: November 2021

Background

Dental technicians are at high risk of pneumoconiosis, usually driven by inhalation of mixed dusts, including metals. An etiological diagnosis is not easy to be performed, particularly in advanced stages.

Case presentation

We describe the case of an early pneumoconiosis occurring in a 47-year-old dental technician who developed respiratory symptoms shortly after beginning work. She described the work environment as dusty and lacking relevant primary prevention tools. A chest CT showed multiple peripheral pseudonodular lesions in both lower lobes; bronchoalveolar lavage and bronchial aspirate evidenced numerous macrophages with reflective metal bodies included into the cytoplasm, that at scanning electron microscopy coupled to Energy Dispersive X-Ray Analysis resulted Zirconium and Aluminum, whereas Tungsten (W) was localized outside cells. End of shift urinary concentrations of W were substantially raised as compared to pre-shift (1.1 vs. 0.2 µg/L).

Conclusions

We concluded for diagnosis of early work-related pneumoconiosis due to abnormal occupational exposure to metals. The case demonstrates the need also for dental professionals to comply with industrial hygiene standards and to be monitored by occupational health physicians.
Durations of asymptomatic, symptomatic, and care-seeking phases of tuberculosis disease with a Bayesian analysis of prevalence survey and notification data
Authors: Ku Chu-Chang , MacPherson Peter , Khundi McEwen , Nzawa Soko Rebecca H. , Feasey Helena R. A. , Nliwasa Marriott , Horton Katherine C. , Corbett Elizabeth L. , Dodd Peter J.
Published: November 2021

Background

Ratios of bacteriologically positive tuberculosis (TB) prevalence to notification rates are used to characterise typical durations of TB disease. However, this ignores the clinical spectrum of tuberculosis disease and potentially long infectious periods with minimal or no symptoms prior to care-seeking.

Methods

We developed novel statistical models to estimate progression from initial bacteriological positivity including smear conversion, symptom onset and initial care-seeking. Case-detection ratios, TB incidence, durations, and other parameters were estimated by fitting the model to tuberculosis prevalence survey and notification data (one subnational and 11 national datasets) within a Bayesian framework using Markov chain Monte Carlo methods.

Results

Analysis across 11 national datasets found asymptomatic tuberculosis durations in the range 4–8 months for African countries; three countries in Asia (Cambodia, Lao PDR, and Philippines) showed longer durations of > 1 year. For the six countries with relevant data, care-seeking typically began half-way between symptom onset and notification. For Kenya and Blantyre, Malawi, individual-level data were available. The sex-specific durations of asymptomatic bacteriologically-positive tuberculosis were 9.0 months (95% credible interval [CrI]: 7.2–11.2) for men and 8.1 months (95% CrI: 6.2–10.3) for women in Kenya, and 4.9 months (95% CrI: 2.6–7.9) for men and 3.5 months (95% CrI: 1.3–6.2) for women in Blantyre. Age-stratified analysis of data for Kenya showed no strong age-dependence in durations. For Blantyre, HIV-stratified analysis estimated an asymptomatic duration of 1.3 months (95% CrI: 0.3–3.0) for HIV-positive people, shorter than the 8.5 months (95% CrI: 5.0–12.7) for HIV-negative people. Additionally, case-detection ratios were higher for people living with HIV than HIV-negative people (93% vs 71%).

Conclusion

Asymptomatic TB disease typically lasts around 6 months. We found no evidence of age-dependence, but much shorter durations among people living with HIV, and longer durations in some Asian settings. To eradicate TB transmission, greater gains may be achieved by proactively screening people without symptoms through active case finding interventions
The use of the mannitol test as an outcome measure in asthma intervention studies: a review and practical recommendations
Authors: Sverrild Asger , Leadbetter Joanna , Porsbjerg Celeste
Published: November 2021

Background

The mannitol test is an indirect bronchial challenge test widely used in diagnosing asthma. Response to the mannitol test correlates with the level of eosinophilic and mast cell airway inflammation, and a positive mannitol test is highly predictive of a response to anti-inflammatory treatment with inhaled corticosteroids. The response to mannitol is a physiological biomarker that may, therefore, be used to assess the response to other anti-inflammatory treatments and may be of particular interest in early phase studies that require surrogate markers to predict a clinical response. The main objectives of this review were to assess the practical aspects of using mannitol as an endpoint in clinical trials and provide the clinical researcher and respiratory physician with recommendations when designing early clinical trials.

Methods

The aim of this review was to summarise previous uses of the mannitol test as an outcome measure in clinical intervention studies. The PubMed database was searched using a combination of MeSH and keywords. Eligible studies included intervention or repeatability studies using the standard mannitol test, at multiple timepoints, reporting the use of PD15as a measure, and published in English.

Results

Of the 193 papers identified, 12 studies met the inclusion criteria and data from these are discussed in detail. Data on the mode of action, correlation with airway inflammation, its diagnostic properties, and repeatability have been summarised, and suggestions for the reporting of test results provided. Worked examples of power calculations for dimensioning study populations are presented for different types of study designs. Finally, interpretation and reporting of the change in the response to the mannitol test are discussed.

Conclusions

The mechanistic and practical features of the mannitol test make it a useful marker of disease, not only in clinical diagnoses, but also as an outcome measure in intervention trials. Measuring airway hyperresponsiveness to mannitol provides a novel and reproducible test for assessing efficacy in intervention trials, and importantly, utilises a test that links directly to underlying drivers of disease.
Starvation induced autophagy promotes the progression of bladder cancer by LDHA mediated metabolic reprogramming
Authors: Li Tinghao , Tong Hang , Yin Hubin , Luo Yi , Zhu Junlong , Qin Zijia , Yin Siwen , He Weiyang
Published: November 2021

Background

Aberrant autophagy and preternatural elevated glycolysis are prevalent in bladder cancer (BLCA) and are both related to malignant progression. However, the regulatory relationship between autophagy and glycolytic metabolism remains largely unknown. We imitated starvation conditions in the tumour microenvironment and found significantly increased levels of autophagy and aerobic glycolysis, which both regulated the progression of BLCA cells. We further explored the regulatory relationships and mechanisms between them.

Methods

We used immunoblotting, immunofluorescence and transmission electron microscopy to detect autophagy levels in BLCA cells under different treatments. Lactate and glucose concentration detection demonstrated changes in glycolysis. The expression of lactate dehydrogenase A (LDHA) was detected at the transcriptional and translational levels and was also silenced by small interfering RNA, and the effects on malignant progression were further tested. The underlying mechanisms of signalling pathways were evaluated by western blot, immunofluorescence and immunoprecipitation assays.

Results

Starvation induced autophagy, regulated glycolysis by upregulating the expression of LDHA and caused progressive changes in BLCA cells. Mechanistically, after starvation, the ubiquitination modification of Axin1 increased, and Axin1 combined with P62 was further degraded by the autophagy–lysosome pathway. Liberated β-catenin nuclear translocation increased, binding with LEF1/TCF4 and promoting LDHA transcriptional expression. Additionally, high expression of LDHA was observed in cancer tissues and was positively related to progression.

Conclusion

Our study demonstrated that starvation-induced autophagy modulates glucose metabolic reprogramming by enhancing Axin1 degradation and β-catenin nuclear translocation in BLCA, which promotes the transcriptional expression of LDHA and further malignant progression.
First comprehensive proteome analysis of lysine crotonylation in Streptococcus agalactiae, a pathogen causing meningoencephalitis in teleosts
Authors: Chen Xinjin , Fan Bolin , Fan Chenlong , Wang Zhongliang , Wangkahart Eakapol , Huang Yucong , Huang Yu , Jian Jichang , Wang Bei
Published: November 2021

Backgroud

Streptococcus agalactiae is a common colonizer of the rectovaginal tract and lead to infectious diseases of neonatal and non-pregnant adults, which also causes infectious disease in fish and a zoonotic risk as well. Lysine crotonylation (Kcr) is a kind of histone post-translational modifications discovered in 2011. In yeast and mammals, Kcr function as potential enhancers and promote gene expression. However, lysine crotonylation in S. agalactiae has not been studied yet.

Methods

In this study, the crotonylation profiling of fish pathogen, S. agalactiae was investigated by combining affinity enrichment with LC MS/MS. The Kcr modification of several selected proteins were further validated by Western blotting.

Results

In the present study, we conducted the proteome-wide profiling of Kcr in S. agalactiae and identified 241 Kcr sites from 675 screened proteins for the first time. Bioinformatics analysis showed that 164 sequences were matched to a total of six definitively conserved motifs, and many of them were significantly enriched in metabolic processes, cellular process, and single-organism processes. Moreover, four crotonylation modified proteins were predicted as virulence factors or to being part of the quorum sensing system PTMs on bacteria. The data are available via ProteomeXchange with identifier PXD026445.

Conclusions

These data provide a promising starting point for further functional research of crotonylation in bacterial virulence in S. agalactiae.
Extraperitoneal laparoscopy for para-aortic lymphadenectomy in endometrial carcinoma staging: an approach with higher efficiency
Authors: Zhang Wei , Xia Lingfang , Han Xiaotian , Ju Xingzhu , Wu Xiaohua , Chen Xiaojun
Published: November 2021

Background

Removing more inframesenteric nodes is not only significantly increases the likelihood of finding metastasis for endometrial cancer, but also can add survival advantage. As most patients diagnosed with endometrial cancer are overweight or obesity, a high efficiency approach is important. Aim of this study was to compare the surgical outcomes of extraperitoneal laparoscopic, transperitoneal laparoscopic, and laparotomic para-aortic lymphadenectomy in endometrial carcinoma staging.

Methods

We retrospectively reviewed data of all patients diagnosed with primary endometrial carcinoma who were treated at the Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center from 1 January 2017 to 31 December 2019. The numbers of para-aortic lymph nodes, surgical time, complications, blood loss and hospital stay were compared. The patients’ medical records and pathological reports were carefully reviewed. Statistical significance was defined as p < 0.05.

Results

We retrospectively compared patients who underwent extraperitoneal laparoscopy (Group E, n = 20), transperitoneal laparoscopy (group T, n = 21), and laparotomy (group L, n = 135). The median number of para-aortic lymph nodes was significantly higher in group E than in groups T and L (9.5, 5, and 6, respectively; p = 0.004 and 0.0004, respectively). All patients in group E underwent successfully dissection to the renal vessel level. The median operation time was significantly shorter in group L than in groups T and E (94, 174, and 233 min, respectively; p < 0.0001). The median estimated blood loss volume was higher in group L than in groups T and E (200, 100, and 142.5 ml, respectively; all comparisons p < 0.001), and the length of hospital stay was significantly longer in group L than in Groups T and E (6, 5, and 6 days, respectively; all comparisons p < 0.001).

Conclusion

The extraperitoneal laparoscopic approach for staging endometrial carcinoma harvested higher numbers of para-aortic lymph nodes which could be considered for endometrial carcinoma staging, especially for para-aortic lymph node harvest.
Correlation between schistosomiasis and CD8+ T cell and stromal PD-L1 as well as the different prognostic role of CD8+ T cell and PD-L1 in schistosomal-associated colorectal cancer and non-schistosomal-associated colorectal cancer
Authors: Wang Weixia , Jing Hongyan , Liu Jican , Bu Dacheng , Zhang Yingyi , Zhu Ting , Lu Kui , Xu Yanchao , Cheng Meihong , Liu Jing , Yao Junxia , Huang Sinian , Wang Limei
Published: November 2021

Background

The effect of schistosomiasis on CD8+ T cells and then on PD-L1 expression was unknown, and the utility of CD8+ TILs as a biomarker for schistosomal-associated colorectal cancer (SCRC) rarely has been reported.

Methods

Three hundred thirty-eight patients with colorectal cancer (CRC) were enrolled. Immunohistochemical analysis was conducted to evaluate the expression of PD-L1 and the infiltration of CD8+ T cells.

Results

In the total cohort, the results showed that CD8+ TIL density was positively correlated with tumoral (p = 0.0001) and stromal PD-L1 expression (p = 0.0102). But there were no correlation between schistosomiasis and CD8+ TILs and PD-L1. Furthermore, CD8+ TIL density (p = 0.010), schistosomiasis (p = 0.042) were independent predictive factors for overall survival (OS). Stromal PD-L1 (sPD-L1) was correlated with OS (p = 0.046), but it was not an independent predictor. In patients without schistosomiasis, CD8 + T cells (p = 0.002) and sPD-L1 (p = 0.005) were associated with better OS. In patients with schistosomiasis, CD8 + T cells were independent prognosis factor (p = 0.045).

Conclusions

The study showed that CD8+ TILs was an independent predictive factor for OS in CRC and SCRC patients. The expression of PD-L1 was positively associated with CD8 + TILs density. There were no correlation between schistosomiasis and CD8 + TILs and PD-L1. Stromal PD-L1 but not tPD-L1 was significantly associated with OS, whereas it was not an independent prognostic factor.
Contextual reprogramming of CAR-T cells for treatment of HER2+ cancers
Authors: Yang Zhifen , Li Lingyu , Turkoz Ahu , Chen Pohan , Harari-Steinfeld Rona , Bobbin Maggie , Stefanson Ofir , Choi Hana , Pietrobon Violena , Alphson Bennett , Goswami Angshumala , Balan Vitaly , Kearney Alper , Patel Dharmesh , Yang Jin , Inel Damla , Vinod Veena , Cesano Alessandra , Wang Bing , Roh Kyung-Ho , Qi Lei S. , Marincola Francesco M.
Published: November 2021

Background

Adoptive transfer of chimeric antigen receptor (CAR)-engineered T cells combined with checkpoint inhibition may prevent T cell exhaustion and improve clinical outcomes. However, the approach is limited by cumulative costs and toxicities.

Methods

To overcome this drawback, we created a CAR-T (RB-340-1) that unites in one product the two modalities: a CRISPR interference-(CRISPRi) circuit prevents programmed cell death protein 1 (PD-1) expression upon antigen-encounter. RB-340-1 is engineered to express an anti-human epidermal growth factor receptor 2 (HER2) CAR single chain variable fragment (scFv), with CD28 and CD3ζ co-stimulatory domains linked to the tobacco etch virus (TEV) protease and a single guide RNA (sgRNA) targeting the PD-1 transcription start site (TSS). A second constructs includes linker for activation of T cells (LAT) fused to nuclease-deactivated spCas9 (dCas9)-Kruppel-associated box (KRAB) via a TEV-cleavable sequence (TCS). Upon antigen encounter, the LAT-dCas9-KRAB (LdCK) complex is cleaved by TEV allowing targeting of dCas9-KRAB to the PD-1 gene TSS.

Results

Here, we show that RB-340-1 consistently demonstrated higher production of homeostatic cytokines, enhanced expansion of CAR-T cells in vitro, prolonged in vivo persistence and more efficient suppression of HER2+ FaDu oropharyngeal cancer growth compared to the respective conventional CAR-T cell product.

Conclusions

As the first application of CRISPRi toward a clinically relevant product, RB-340-1 with the conditional, non-gene editing and reversible suppression promotes CAR-T cells resilience to checkpoint inhibition, and their persistence and effectiveness against HER2-expressing cancer xenografts.
DSS-induced inflammation in the colon drives a proinflammatory signature in the brain that is ameliorated by prophylactic treatment with the S100A9 inhibitor paquinimod
Authors: Talley Sarah , Valiauga Rasa , Anderson Lillian , Cannon Abigail R. , Choudhry Mashkoor A. , Campbell Edward M.
Published: November 2021

Background

Inflammatory bowel disease (IBD) is established to drive pathological sequelae in organ systems outside the intestine, including the central nervous system (CNS). Many patients exhibit cognitive deficits, particularly during disease flare. The connection between colonic inflammation and neuroinflammation remains unclear and characterization of the neuroinflammatory phenotype in the brain during colitis is ill-defined.

Methods

Transgenic mice expressing a bioluminescent reporter of active caspase-1 were treated with 2% dextran sodium sulfate (DSS) for 7 days to induce acute colitis, and colonic, systemic and neuroinflammation were assessed. In some experiments, mice were prophylactically treated with paquinimod (ABR-215757) to inhibit S100A9 inflammatory signaling. As a positive control for peripheral-induced neuroinflammation, mice were injected with lipopolysaccharide (LPS). Colonic, systemic and brain inflammatory cytokines and chemokines were measured by cytokine bead array (CBA) and Proteome profiler mouse cytokine array. Bioluminescence was quantified in the brain and caspase activation was confirmed by immunoblot. Immune cell infiltration into the CNS was measured by flow cytometry, while light sheet microscopy was used to monitor changes in resident microglia localization in intact brains during DSS or LPS-induced neuroinflammation. RNA sequencing was performed to identify transcriptomic changes occurring in the CNS of DSS-treated mice. Expression of inflammatory biomarkers were quantified in the brain and serum by qRT-PCR, ELISA and WB.

Results

DSS-treated mice exhibited clinical hallmarks of colitis, including weight loss, colonic shortening and inflammation in the colon. We also detected a significant increase in inflammatory cytokines in the serum and brain, as well as caspase and microglia activation in the brain of mice with ongoing colitis. RNA sequencing of brains isolated from DSS-treated mice revealed differential expression of genes involved in the regulation of inflammatory responses. This inflammatory phenotype was similar to the signature detected in LPS-treated mice, albeit less robust and transient, as inflammatory gene expression returned to baseline following cessation of DSS. Pharmacological inhibition of S100A9, one of the transcripts identified by RNA sequencing, attenuated colitis severity and systemic and neuroinflammation.

Conclusions

Our findings suggest that local inflammation in the colon drives systemic inflammation and neuroinflammation, and this can be ameliorated by inhibition of the S100 alarmin, S100A9.
An ancient retroviral RNA element hidden in mammalian genomes and its involvement in co-opted retroviral gene regulation
Authors: Kitao Koichi , Nakagawa So , Miyazawa Takayuki
Published: November 2021

Background

Retroviruses utilize multiple unique RNA elements to control RNA processing and translation. However, it is unclear what functional RNA elements are present in endogenous retroviruses (ERVs). Gene co-option from ERVs sometimes entails the conservation of viral cis-elements required for gene expression, which might reveal the RNA regulation in ERVs.

Results

Here, we characterized an RNA element found in ERVs consisting of three specific sequence motifs, called SPRE. The SPRE-like elements were found in different ERV families but not in any exogenous viral sequences examined. We observed more than a thousand of copies of the SPRE-like elements in several mammalian genomes; in human and marmoset genomes, they overlapped with lineage-specific ERVs. SPRE was originally found in human syncytin-1 and syncytin-2. Indeed, several mammalian syncytin genes: mac-syncytin-3 of macaque, syncytin-Ten1 of tenrec, and syncytin-Car1 of Carnivora, contained the SPRE-like elements. A reporter assay revealed that the enhancement of gene expression by SPRE depended on the reporter genes. Mutation of SPRE impaired the wild-type syncytin-2 expression while the same mutation did not affect codon-optimized syncytin-2, suggesting that SPRE activity depends on the coding sequence.

Conclusions

These results indicate multiple independent invasions of various mammalian genomes by retroviruses harboring SPRE-like elements. Functional SPRE-like elements are found in several syncytin genes derived from these retroviruses. This element may facilitate the expression of viral genes, which were suppressed due to inefficient codon frequency or repressive elements within the coding sequences. These findings provide new insights into the long-term evolution of RNA elements and molecular mechanisms of gene expression in retroviruses.
Commentary: What should referral pathways have to improve healthcare experiences of women with female genital mutilation in Australia?
Authors: Njue Carolyne , Ameyaw Edward K. , Ahinkorah Bright O. , Seidu Abdul-Aziz , Kimani Samuel
Published: November 2021

Background

We examined the evidence derived from healthcare professionals’ interfacing with women with female genital mutilation (FGM) to comprehend the referral pathways available to these women in Australia.

Main body

Clinicians encountered FGM-related complications that included ruptured bladder and total urinary incontinence. Midwives and paediatricians indicated a lack of referral pathways for FGM, but used their discretion to refer such cases to social work departments, obstetric/gynaecological units, child protection service providers, psychological counsellors and surgeons. The continuum of care for women with FGM is characterised by inadequate and lack of clear referral pathways. This underscores the need to develop and strengthen referral pathways in response to physical, birthing and psychological complications of women with FGM to improve their care experiences in Australia.

Short conclusion

Capacity building initiatives on FGM-prevention and care for trainees and practising health providers and community involvement in high burden areas/populations should be implemented to promote uptake and utilization of the referral services. Provision of infrastructural support, including clinical management tools, job aids, posters, referral algorithms and electronic patient records with "drop-down menus" for referral sites for health complications of FGM to reinforce the providers’ efforts are critical.
Magnitude of child sexual abuse and its associated factors among high school female students in Dire Dawa, Eastern Ethiopia: a cross-sectional study
Authors: Abera Legesse , Aliye Abdulahi , Tadesse Kalbesse , Guta Alemu
Published: November 2021

Background

Child sexual abuse (CSA) refers to the involvement of a child (< 18 years) in sexual activity that he or she does not fully comprehend, is unable to give informed consent to, or for which the child is not developmentally prepared and cannot give consent, or that violates the laws or social taboos of society. It is a serious public health problem affecting millions of people each year worldwide but the most neglected and least documented form of violence in Ethiopia among school girls. Therefore, this study aimed to assess the magnitude of child sexual abuse and its associated factors among female high school students in the Dire Dawa administration, Eastern Ethiopia.

Methods

An institutional-based cross-sectional study was conducted among female high school students in Dire Dawa administration between March 1 and 23/2021. We employed stratified and multistage sampling techniques to include 794 participants from selected high schools. A pretested self-administered questionnaire was used, and the data were analyzed using the SPSS software version 24.

Results

The proportion of students who reported at least one form of sexual abuse was 384 (48.9%) and approximately 19% of the students reported rape from the total respondents. Students who live alone 4.3 times (AOR 4.30; 95% CI 1.81–10.24), those who live with their friends five times (AOR 5.02; 95% CI 2.24–8.04), and those who live with their single parent three times (AOR 3.31; 95% CI 1.23–8.89) more likely to experience sexual abuse than those living with both parents. The odds of experiencing sexual abuse among students of rural residence were 3.2 times higher than their urban counterparts (AOR 3.2; 95% CI 2.02–4.51). Students who didn’t drink alcohol were 70% more protective than those who drank alcohol (AOR 0.70; 95% CI 0.28–0.97). Among rape survivors (64, 37.9%) developed unwanted pregnancies, 26.0% of them underwent an abortion, and (39, 26.0%) developed STI as an outcome of sexual abuse.

Conclusion

This study demonstrated that the magnitude of child sexual abuse among female students in Dire Dawa was high. Lack of discussion about sexual issues with parents, living without both parents, drinking alcohol, and being a rural residence had a significant association with child sexual abuse. Unwanted pregnancy, abortion, and STIs have been reported as reproductive health outcomes of rape. Therefore, policymakers should introduce and strengthen comprehensive sexual and reproductive health education both in school and out of school, in addition to formal education to reduce the magnitude of the problem. Parents should discuss all sexual and reproductive health issues with their children to reduce the magnitude and consequences of child sexual abuse.
High throughput sequencing of whole transcriptome and construct of ceRNA regulatory network in RD cells infected with enterovirus D68
Authors: Si Junzhuo , Tang Xia , Xu Lei , Fu Huichao , Li Huayi , He Yonglin , Bao Jiajia , Tang Jialing , Li Anlong , Lu Nan , Yang Chun
Published: November 2021

Background

With the advancement of sequencing technologies, a plethora of noncoding RNA (ncRNA) species have been widely discovered, including microRNAs (miRNAs), circular RNAs (circRNAs), and long ncRNAs (lncRNAs). However, the mechanism of these non-coding RNAs in diseases caused by enterovirus d68 (EV-D68) remains unclear. The goal of this research was to identify significantly altered circRNAs, lncRNAs, miRNAs, and mRNAs pathways in RD cells infected with EV-D68, analyze their target relationships, demonstrate the competing endogenous RNA (ceRNA) regulatory network, and evaluate their biological functions.

Methods

The total RNAs were sequenced by high-throughput sequencing technology, and differentially expressed genes between control and infection groups were screened using bioinformatics method. We discovered the targeting relationship between three ncRNAs and mRNA using bioinformatics methods, and then built a ceRNA regulatory network centered on miRNA. The biological functions of differentially expressed mRNAs (DEmRNAs) were discovered through GO and KEGG enrichment analysis. Create a protein interaction network (PPI) to seek for hub mRNAs and learn more about protein–protein interactions. The relative expression was verified using RT-qPCR. The effects of Fos and ARRDC3 on virus replication were confirmed using RT-qPCR, virus titer (TCID50/ml), Western blotting.

Results

375 lncRNAs (154 upregulated and 221 downregulated), 33 circRNAs (32 upregulated and 1 downregulated), 96 miRNAs (49 upregulated and 47 downregulated), and 239 mRNAs (135 upregulated and 104 downregulated) were identified as differently in infected group compare to no-infected group. A single lncRNA or circRNA can be connected with numerous miRNAs, which subsequently coregulate additional mRNAs, according to the ceRNA regulatory network. The majority of DEmRNAs were shown to be connected to DNA binding, transcription regulation by RNA polymerase II, transcription factor, MAPK signaling pathways, Hippo signal pathway, and apoptosis pathway, according to GO and KEGG pathway enrichment analysis. The hub mRNAs with EGR1, Fos and Jun as the core were screened through PPI interaction network. We preliminarily demonstrated that the Fos and ARRDC3 genes can suppress EV-D68 viral replication in order to further verify the results of full transcriptome sequencing.

Conclusion

The results of whole transcriptome analysis after EV-D68 infection of RD cells were first reported in this study, and for the first time, a ceRNA regulation network containing miRNA at its center was established for the first time. The Fos and ARRDC3 genes were found to hinder viral in RD cells. This study establishes a novel insight host response during EV-D68 infection and further investigated potential drug targets.
Developing and validating a measurement tool to self-report perceived barriers in substance use treatment: the substance use treatment barriers questionnaire (SUTBQ)
Authors: Ghouchani Hamid Tavakoli , Lashkardoost Hossein , Saadati Hassan , Hojjat Seyed Kaveh , Kaviyani Faezeh , Razaghi Kazem , Asghari Dordane , Gholizadeh Nazanin
Published: November 2021

Background

Substance using often cause a wide range of social, health, and psychological problems. This study aimed to develop and validate a questionnaire of barriers of treatment in substance users.

Methods

In this cross-sectional study, the initial questionnaire was designed based on the evaluation of previous studies. The preliminary tool including 35 Likert-scaled items. After assuring the face validity of the questionnaire, 13 experts’ opinions were obtained for assessing or improving the content validity. The reliability was investigated by internal consistency methods using Cronbach’s alpha. For measuring the structural validity, the exploratory factor analysis was performed to determine the dimensionality of the questionnaire using principal components extraction and Varimax rotation.

Results

The preliminary questionnaire consisted of 35 items. After completing the face validity and summarizing the experts’ suggestions, 8 items were removed. By calculating the content validity ratio and coefficient, 11 questions were deleted. The internal consistency was calculated to be 0.84 using Cronbach’s alpha. In the last stage and according to the results of the factor analysis, three factors fear of or unawareness of treatment, doubt or inefficiency, and social stigma were identified from the 10-items questionnaire, which explained 67.34% of the total variance.

Conclusion

Considering the necessity of using a validated tool for planning and evaluating effective interventions on people who use substance is inevitable. The Substance use Treatment Barriers Questionnaire is designed with 10 items and 3 dimensions, which has appropriate validity and reliability and can be used to determine the obstacles for treatment or factors that lead to discontinuing treatment.
Study on the relationship between the timing of conversion from external fixation to internal fixation and infection in the treatment of open fractures of extremities
Authors: Ye Zelin , Zhao Shanwen , Zeng Canjun , Luo Ziheng , Yuan Song , Li Runguang
Published: November 2021

Objective

To investigate the relationship between the infection rate and the timing of replacement of temporary external fixators with internal fixation, and the timing of immediate or delayed internal fixation after removal of temporary external fixation in the staging treatment modality of open fractures of extremities.

Methods

A retrospective analysis was performed on 122 cases of open fractures of extremities. External fixators were applied at the early stage and replaced with internal fixation when the condition of soft tissues improved and inflammatory indexes dropped to the normal range or showed a steady downward trend. Depending on the carrying time of external fixators after wound closure or healing, the patients were divided into three groups; the carrying time of groups A, B, and C was ≤ 14 days, 15–28 days, and > 28 days, respectively. Depending on the immediate or delayed internal fixation after removal of external fixator, patients were divided into group a (immediate internal fixation after removal of external fixator) and group b (delayed internal fixation after removal of external fixator, 5–7 days later).

Results

The infection rates of groups A, B, and C were 6.5%, 5.9%, and 23.3%, respectively. The differences among the three groups were statistically significant (P < 0.05). The infection rates of different Gustilo–Anderson fractures were as follows: no cases of infection out of 10 cases with type I fracture (0%); two cases of infection out of 35 cases with type II fracture (5.7%); three cases of infection out of 36 cases with IIIa fracture (8.3%); five cases of infection out of 28 cases with IIIB fracture (17.9%); and five cases of infection out of 13 cases with IIIC fracture (38.5%). The differences among the five groups were statistically significant.

Conclusions

The occurrence of infection of open fractures of extremities is associated with the fracture severity (Gustilo classification). For open fractures of Gustilo types I and II, the final internal fixation should be placed as soon as possible when the recovery of general and local conditions is good and the infection is controlled.
Silencing of UBE2D1 inhibited cell migration in gastric cancer, decreasing ubiquitination of SMAD4
Authors: Xie Honghu , He Yu , Wu Yugang , Lu Qicheng
Published: November 2021

Background

Gastric cancer (GC) is the second leading cause of cancer-related deaths. Because it is hard to diagnose at early stage, the overall 5 years survival rate is lower than 25%. High migration is the main hallmark of malignant cells at advanced stage of GC. Thus, it is urgent to find biomarkers for early diagnosis and more effective therapy of GC.

Methods

In this study, lentivirus-mediated silencing and overexpression lentiviruses targeting the ubiquitin-conjugating enzyme E2 D1 (UBE2D1), transwell, wound healing, and pulmonary metastasis mouse model were applied to analyze the function of UBE2D1 in vitro and in vivo. Real-time PCR and immunohistochemistry were used to elucidate the level of UBE2D1 in GC samples.

Results

Silencing of UBE2D1 inhibited cell migration and the levels of epithelial-mesenchymal transition makers (MMP2 and MMP9) in AGS and MKN45 cells. Silencing of UBE2D1 inhibited cell metastasis in mouse model. On the contrary, UBE2D1 overexpression increased cell migration and the levels of MMP2 and MMP9 in MGC-803 cells. Further, silencing of UBE2D1 decreased the ubiquitination level of mothers against decapentaplegic homolog 4 (SMAD4), and the increase of cell migration induced by UBE2D1 overexpression could be reversed by SMAD4.

Conclusion

Silencing of UBE2D1 inhibited cell migration through transforming growth factor β (TGF-β)/SMAD4 signaling pathway in GC.