bluuebunny/crossref_metadata_2025 huggingface dataset:
Double rarity: malignant masquerade biliary stricture in a situs inversus totalis patient
Authors: Eitler K. , Mathe Z. , Papp V. , Zalatnai A. , Bibok A. , Deak P. A. , Kobori L. , Telkes G.
Published: March 2021

Background

Situs inversus totalis is a rare anatomical variation of both the thoracic and the abdominal organs. Common bile duct strictures can be caused by malignant and benign diseases as well. 7–18% of the latter ones are 'malignant masquerade’ cases, as pre-operative differentiation is difficult.

Case presentation

We present the case of a 68y male patient with known situs inversus totalis and a recent onset of obstructive jaundice caused by a malignant behaving common bile duct stricture. Technically difficult endoscopic retrograde cholangiopancreatography, brush cytology, magnetic resonance cholangiopancreatography, endoscopic ultrasound, and percutaneous transhepatic drainage with stent implantation were performed for proper diagnosis. Cholecystectomy, common bile duct resection with hilar lymphadenectomy, and hepatico-jejunostomy have been performed following multidisciplinary consultation. The final histology report did not confirm any clear malignancy, the patient is doing well.

Conclusion

In situs inversus patients, both diagnostic and therapeutic procedures can lead to various difficulties. Benign biliary strictures are frequently misdiagnosed preoperatively as cholangiocellular carcinoma. Surgery is usually unavoidable, involving a significant risk of complications. The co-existence of these two difficult diagnostic and therapeutic features made our case challenging.
The inguinal hernia management in Costa Rica according to a survey between surgeons: result comparison with 2018 International Groin Hernia Guidelines
Authors: Martínez-Hoed Jesús , Cordero-Bermúdez Katherine , García-Pastor Providencia , Pous-Serrano Salvador , Ortiz-Cubero José A.
Published: March 2021

Background

Inguinal hernia surgery is a frequent procedure among general surgeons in Costa Rica, but the management and technique are not uniform. The International Guideline for Groin Hernia management was published in 2018 to standardize the inguinal hernia surgery, but the diffusion of the guidelines and its adherence have been extremely varied.

Purpose

Collect and analyze the current reality regarding groin hernia management in Costa Rica. Secondly evaluate the diffusion and development comparing it to the guideline’s recommendations.

Method

Questionnaire of 42 single and multiple answer questions according to the topics of the International Guideline directed
to general surgeons. Diffusion of the inquiry through surgical and hernia association chats and email. Timeframe June–December 2019.

Results

64 surveys were collected, which is a representative number of the general surgeons national college. The most frequent procedure between these was the abdominal wall surgery. Every surgeon did more than 52 groin hernia surgeries in one year, most of them outpatients. The epidural anesthesia was used the most and Lichtenstein’s technique was the most frequently used (64%). 68% of the surgeons know how to perform a minimally invasive inguinal hernia surgery but with variable volumes. 38% of participants considered themselves experts in groin hernia management and 52% did not know the 2018 International Guideline. The recommendations of such guideline are followed only partially.

Conclusions

The 2018 Hernia Surge International Guidelines have low diffusion among Costa Rican surgeons. The laparoscopic approach is widely accepted but there are no studies to assess the results and the quality. There should be protocols and studies adapted to Costa Rica’s national situation.
The effect of fibrin glue on the postoperative lymphatic leakage after D2-lymphadenectomy and gastrectomy in patients with gastric cancer
Authors: Mahmoodzadeh Habibollah , Rahimi-Movaghar Ehsanollah , Omranipour Ramesh , Shirkhoda Mohammad , Jalaeefar Amirmohsen , Miri Seyed Rouhollah , Sharifi Amirsina
Published: March 2021

Introduction

Disturbance in the lymphatic drainage during D2 dissection is associated with significant morbidity. We aimed to assess the effect of fibrin glue on the reduction of postoperative lymphatic leakage.

Methods

Prospective double-blinded randomized clinical trial with forty patients in each study arm was conducted. All patients diagnosed, staged, and became a candidate for D2 dissection based on NCCN 2019 guideline for gastric cancer. The intervention group received 1 cc of IFABOND® applied to the surgical bed.

Results

The difference between study groups regarding age, gender, tumor stage was insignificant. (All p-values > 0.05). The median daily drainage volume was 120 ml with the first and the third interquartile being 75 and 210 ml, respectively for the intervention group. The control group had median, the first, and the third interquartile of 350, 290, and 420 ml. The difference between daily drainage volumes was statistically significant (p-value < 0.001). The length of hospital stay was significantly different between the two groups. Notably, the intervention group was discharged sooner (median of 7 Vs 9 days, p-value: 0.001).

Conclusion

This study showed the possible role of fibrin glue in reducing postoperative lymphatic leakage after gastrectomy and D2 dissection.

Registration trial number: IRCT20200710048071N1, 2020.08.16
Hyperprogressive disease after radiotherapy combined with anti-PD-1 therapy in renal cell carcinoma: a case report and review of the literature
Authors: Liu Chao , Piao Jingjing , Shang Zhiyang
Published: March 2021

Background

Studies have shown that immune checkpoint inhibitors (ICIs) have limited efficacy and can even increase tumour burden in short time periods. This is usually called hyperprogressive disease (HPD). To date, there are few reports regarding HPD; fewer have analysed the relationship between HPD and radiotherapy combined with ICIs, and their conclusions are controversial.

Case presentation

A 42-year-old woman was diagnosed with stage IV renal clear cell carcinoma. The patient had previously received sorafenib and pazopanib as first- and second-line therapies, respectively. She received radiotherapy combined with nivolumab. Eighteen days after administration of the third dose of nivolumab, the patient’s general condition deteriorated; this was associated with immune-related adverse events. Computed tomography showed that the diameter of left lung metastases had sharply increased. A biopsy of the lung metastasis showed no infiltration of lymphocytes. The patient’s general condition worsened and she died of the disease on the 70th day after administration of the third dose of nivolumab.

Conclusions

This report describes the development of HPD following the administration of radiotherapy combined with ICIs in a case of advanced renal cell carcinoma. The case indicates that radiotherapy may show bidirectional regulation effects on anti-tumour immune response. If the immunosuppressive function of radiotherapy is dominant, combined with ICIs, it could result in HPD.
A case report of bladder and intestinal endometriosis, and the relationship between sex hormone receptor expression and PIK3CA mutation analysis
Authors: Kanto Akiko , Kotani Yasushi , Murakami Kosuke , Miyagawa Chiho , Nakai Hidekatsu , Matsumura Noriomi
Published: March 2021

Background

Extragonadal endometriosis is a rare condition, and its disease manifestation and long-term prognosis have not been elucidated. We report an extragonadal endometriosis case controlled by drug therapy for 14 years with analysis of the sex hormone receptor expression and PIK3CA mutation.

Case presentation

The patient was diagnosed with bladder endometriosis at age of 30 years, and underwent bilateral nephrostomy and GnRHa therapy with add-back therapy. The patient was switched to dienogest therapy at age 35 and had hematuria and bloody stools at age 38. PET-CT revealed a 6-cm mass in the bladder with fluorodeoxyglucose accumulation and the diagnosis of endometriosis in the bladder, sigmoid colon, and cecum was confirmed after the biopsy result. The lesion’s tubular structures were positive for the estrogen receptor, but only 30% positive for the progesterone receptor, and the H1047R mutation in PIK3CA was found in tubular structures of the bladder lesion. GnRHa therapy caused the tumors to shrink.

Conclusion

Decreased progesterone receptor expression and oncogenic mutations may influence the course of less common and rare site endometriosis. Rare site endometriosis often requires long-term hormone therapy, and management should be tailored to the patient's life stage, keeping in mind complications, such as decreased bone density.
Consistency of decision support software-integrated telephone triage and associated factors: a systematic review
Authors: Islam Farah , Sabbe Marc , Heeren Pieter , Milisen Koen
Published: March 2021

Background

In the recent decades, the use of computerized decision support software (CDSS)-integrated telephone triage (TT) has become an important tool for managing rising healthcare demands and overcrowding in the emergency department. Though these services have generally been shown to be effective, large gaps in the literature exist with regards to the overall quality of these systems. In the current systematic review, we aim to document the consistency of decisions that are generated in CDSS-integrated TT. Furthermore, we also seek to map those factors in the literature that have been identified to have an impact on the consistency of generated triage decisions.

Methods

As part of the TRANS-SENIOR international training and research network, a systematic review of the literature was conducted in November 2019. PubMed, Web of Science, CENTRAL, and the CINAHL database were searched. Quantitative articles including a CDSS component and addressing consistency of triage decisions and/or factors associated with triage decisions were eligible for inclusion in the current review. Studies exploring the use of other types of digital support systems for triage (i.e. web chat, video conferencing) were excluded. Quality appraisal of included studies were performed independently by two authors using the Methodological Index for Non-Randomized Studies.

Results

From a total of 1551 records that were identified, 39 full-texts were assessed for eligibility and seven studies were included in the review. All of the studies (n = 7) identified as part of our search were observational and were based on nurse-led telephone triage. Scientific efforts investigating our first aim was very limited. In total, two articles were found to investigate the consistency of decisions that are generated in CDSS-integrated TT. Research efforts were targeted largely towards the second aim of our study—all of the included articles reported factors related to the operator- (n = 6), patient- (n = 1), and/or CDSS-integrated (n = 2) characteristics to have an influence on the consistency of CDSS-integrated TT decisions.

Conclusion

To date, some efforts have been made to better understand how the use of CDSS-integrated TT systems may vary across settings. In general, however, the evidence-base surrounding this field of literature is largely inconclusive. Further evaluations must be prompted to better understand this area of research.

Protocol registration

The protocol for this study is registered in the PROSPERO database (registration number: CRD42020146323).
Association between self-efficacy and general health: a cross-sectional study of the nursing population
Authors: Dadipoor Sakineh , Alavi Azin , Ghaffari Mohtasham , Safari-Moradabadi Ali
Published: March 2021

Background

The present research aimed to explore the association of self-efficacy and general health among nurses.

Methods

This was a descriptive-analytical. A total of 470 nurses were selected through the stratified sampling method. To collect the required data, GSE-10 and GHQ-28 were used. Independent-sample T-test, Pearson correlation coefficient, Chi-squared test, and regression were also used to analyze the obtained data.

Results

The results reveal a statistically significant correlation between general health and self-efficacy (t=-6.72, p < .001). Among general health parameters, social functioning has significantly predicted self-efficacy.

Conclusions

As shown in the present findings, an acceptable level of self-efficacy can positively affect all aspects of nurses’ general health.
Workplace factors associated with mental health of healthcare workers during the COVID-19 pandemic: an international cross-sectional study
Authors: Khajuria Ankur , Tomaszewski Wojtek , Liu Zhongchun , Chen Jian-hua , Mehdian Roshana , Fleming Simon , Vig Stella , Crawford Mike J.
Published: March 2021

Background

The association of workplace factors on mental health of healthcare workers (HCWs) during the COVID-19 pandemic needs to be urgently established. This will enable governments and policy-makers to make evidence-based decisions. This international study reports the association between workplace factors and the mental health of HCWs during the pandemic.

Methods

An international, cross-sectional study was conducted in 41 countries. The primary outcome was depressive symptoms, derived from the validated Patient Health Questionnaire-2 (PHQ-2). Multivariable logistic regression identified factors associated with mental health outcomes. Inter-country differences were also evaluated.

Results

A total of 2527 responses were received, from 41 countries, including China (n = 1213; 48.0%), UK (n = 891; 35.3%), and USA (n = 252; 10.0%). Of all participants, 1343 (57.1%) were aged 26 to 40 years, and 2021 (80.0%) were female; 874 (34.6%) were doctors, and 1367 (54.1%) were nurses. Factors associated with an increased likelihood of depressive symptoms were: working in the UK (OR = 3.63; CI = [2.90–4.54]; p < 0.001) and USA (OR = 4.10; CI = [3.03–5.54]), p < 0.001); being female (OR = 1.74; CI = [1.42–2.13]; p < 0.001); being a nurse (OR = 1.64; CI = [1.34–2.01]; p < 0.001); and caring for a COVID-19 positive patient who subsequently died (OR = 1.20; CI = [1.01–1.43]; p = 0.040). Workplace factors associated with depressive symptoms were: redeployment to Intensive Care Unit (ICU) (OR = 1.67; CI = [1.14–2.46]; p = 0.009); redeployment with perceived unsatisfactory training (OR = 1.67; CI = [1.32–2.11]; p < 0.001); not being issued with appropriate personal protective equipment (PPE) (OR = 2.49; CI = [2.03–3.04]; p < 0.001); perceived poor workplace support within area/specialty (OR = 2.49; CI = [2.03–3.04]; p < 0.001); and perceived poor mental health support (OR = 1.63; CI = [1.38–1.92]; p < 0.001).

Conclusion

This is the first international study, demonstrating that workplace factors, including PPE availability, staff training pre-redeployment, and provision of mental health support, are significantly associated with mental health during COVID-19. Governments, policy-makers and other stakeholders need to ensure provision of these to safeguard HCWs’ mental health, for future waves and other pandemics.
Exploration of the costs of accessing health services: data from a longitudinal study of young people in transition from paediatric to adult services
Authors: Simpson Julija , Robinson Tomos , Vale Luke
Published: March 2021

Background

Economic evaluations that include the patient perspective often base their estimates of patient time and travel costs on data collected at a single point in time. This, however, may be inaccurate if the costs of accessing care change substantially over time, as may be the case for young people in transition from paediatric to adult health services.

Aims

The aim of this study was to explore the differences in these time and travel costs between two data collection points for young individuals in transition between health care services, and thus to provide an insight of whether such costs should be collected more than once.

Methods

Descriptive statistics and regression modelling were used to estimate the average difference in costs between the two points of data collection, as well as the potential drivers of those cost differences.

Results

We found a small difference in costs between the two time points, equal to -£45.78 [95% CI: − 89.70 to − 1.86]. The results were largely driven by changes in the unit cost of visits and in the number of attendances.

Conclusions

A simple and common assumption that patient costs could be collected at a single time point cannot be made in the context of our study. When deciding on the frequency of elicitation of patient costs, future studies should consider the relative impacts of additional data collection on the estimates of efficiency, inequalities and resource implications for collecting new data.
Influence of government-driven quality assessment program on patients with chronic obstructive pulmonary disease
Authors: Park Hye Jung , Kim Sung-Ryeol , Kim Sinae , Lee Hye Sun , Kim Bo Yeon , Kim Hye Kyoung , Ahn Sang In , Shin Ji Hyeon , Lee Jae-Hyun , Park Jung-Won
Published: March 2021

Background

The Korean Health Insurance Review and Assessment Service (HIRA) has launched the Chronic Obstructive Pulmonary Disease (COPD) Quality Assessment Program (CQAP) since 2014. We aimed to reveal the influence of this national program on clinical outcomes and the burden of COPD in Korea.

Methods

The CQAP is conducted annually. We used healthcare claims data linked with the results of the program provided by HIRA between May 2014 and April 2017. Patients were considered to have COPD if they visited a hospital for COPD management during the assessment term. Those who visited a medical institution for COPD and were prescribed COPD medications at least twice were assessed by the CQAP (assessed subjects, AS; not-assessed subjects, NAS). CQAP evaluated the pulmonary function test conduction rate, regular visitation rate, and prescription rates of COPD medications.

Results

Among the 560,000 patients with COPD, about 140,000 were assessed by the CQAP annually. In both groups, the pulmonary function test conduction rate and inhaled bronchodilator prescription rate improved since 2014. Compared to the NAS group, the risk of admission and all-cause mortality rate in the AS group were significantly reduced by 21.2% and 40.7%, respectively. In patients who were assessed for 3 consecutive years, all of the above variables were high at baseline and were not improved much from implementation of CQAP. In matching analysis, we observed this improvement to be limited in the COPD quality assessment year.

Conclusions

The CQAP by the health insurance bureau has improved the management protocol and prognosis of COPD.
The impact of the involvement of a healthcare professional on the usage of an eHealth platform: a retrospective observational COPD study
Authors: van Zelst Cathelijne M. , Kasteleyn Marise J. , van Noort Esther M. J. , Rutten - van Molken Maureen P. M. H. , Braunstahl Gert-Jan , Chavannes Niels H. , in ’t Veen Johannes C. C. M.
Published: March 2021

Background

Ehealth platforms, since the outbreak of COVID-19 more important than ever, can support self-management in patients with Chronic Obstructive Pulmonary Disease (COPD). The aim of this observational study is to explore the impact of healthcare professional involvement on the adherence of patients to an eHealth platform. We evaluated the usage of an eHealth platform by patients who used the platform individually compared with patients in a blended setting, where healthcare professionals were involved.

Methods

In this observational cohort study, log data from September 2011 until January 2018 were extracted from the eHealth platform Curavista. Patients with COPD who completed at least one Clinical COPD Questionnaire (CCQ) were included for analyses (n = 299). In 57% (n = 171) of the patients, the eHealth platform was used in a blended setting, either in hospital (n = 128) or primary care (n = 29). To compare usage of the platform between patients who used the platform independently or with a healthcare professional, we applied propensity score matching and performed adjusted Poisson regression analysis on CCQ-submission rate.

Results

Using the eHealth platform in a blended setting was associated with a 3.25 higher CCQ-submission rate compared to patients using the eHealth platform independently. Within the blended setting, the CCQ-submission rate was 1.83 higher in the hospital care group than in the primary care group.

Conclusion

It is shown that COPD patients used the platform more frequently in a blended care setting compared to patients who used the eHealth platform independently, adjusted for age, sex and disease burden. Blended care seems essential for adherence to eHealth programs in COPD, which in turn may improve self-management.
Anti‐malarial drug effects on parasite dynamics in vivax malaria
Authors: White Nicholas J.
Published: March 2021

Relapses of Plasmodium vivax malaria are prevented by 8-aminoquinolines. If hypnozoites survive, then the subsequent blood stage infections in early relapses (< 2 months) are suppressed by the slowly eliminated anti-malarial drugs used to treat the blood stage infection (chloroquine, artemisinin combination treatments), but they are not usually eliminated. The 8-aminoquinolines have significant blood stage activity which contributes to therapeutic responses. The latent interval from primary infection to early relapse depends on the number of activatable hypnozoites, the dose of anti-malarial, its pharmacokinetic properties, the level of resistance (minimum inhibitory concentration) and immunity. The dose–response relationship for radical curative efficacy of primaquine and tafenoquine is steep over the total dose range from 1.5 to 5 mg base/kg which may explain the poor efficacy of tafenoquine at the currently recommended dose.
Cross-cultural adaptation and psychometric properties of the Mexican version of the Early Childhood Oral Health Impact Scale (ECOHIS)
Authors: Montoya Alba Lilia Brambila , Knorst Jessica Klöckner , Uribe Isaac Murisi Pedroza , González Rubén Alberto Bayardo , Ardenghi Thiago Machado , Sánchez Carmen Celina Alonso
Published: March 2021

Background

Instruments adapted for the Mexican population to assess oral health-related quality of life (OHRQoL) in preschoolers remain lacking. This study aimed to cross-culturally adapt and evaluate the psychometric properties of the Mexican version of the Early Childhood Oral Health Impact Scale (M-ECOHIS).

Methods

This cross-sectional study was conducted with preschool children from southern Mexico. The investigation was divided into a transcultural adaptation phase and a validation phase. The M-ECOHIS was completed by the children’s guardians, and clinical data were also evaluated. Reliability was evaluated using tests of internal consistency and test–retest measures, while construct validity was assessed through Spearman’s correlation coefficient between M-ECOHIS scores and self-reported oral health, and through confirmatory factor analysis (CFA). Construct validity was also evaluated through discriminant validity of the M-ECOHIS, which was determined according to questionnaire scores on oral health measures (e.g., dental caries).

Results

A total of 303 preschool children participated in this study. Regarding internal consistency, Cronbach’s alpha was > 0.78 for the child section, family section, and general M-ECOHIS. The general intraclass correlation coefficient (ICC) for test–retest reliability was 0.95. The correlation between the scores obtained on the child and family impact sections was significant with the self-reported oral health status rating. In relation to CFA, all items of the M-ECOHIS confirmed the latent variables. Further, M-ECOHIS scores were associated with the presence of untreated dental caries, indicating that the questionnaire has good discriminant validity.

Conclusion

Our findings suggest that the M-ECOHIS is a valid and reliable instrument for assessing the impact of oral health on quality of life in Mexican preschool children.
GRP78 in lung cancer
Authors: Xia Shengkai , Duan Wenzhe , Liu Wenwen , Zhang Xinri , Wang Qi
Published: March 2021

Glucose-regulating protein 78 (GRP78) is a molecular chaperone in the endoplasmic reticulum (ER) that promotes folding and assembly of proteins, controls the quality of proteins, and regulates ER stress signaling through Ca2+ binding to the ER. In tumors, GRP78 is often upregulated, acting as a central stress sensor that senses and adapts to changes in the tumor microenvironment, mediating ER stress of cancer cells under various stimulations of the microenvironment to trigger the folding protein response. Increasing evidence has shown that GRP78 is closely associated with the progression and poor prognosis of lung cancer, and plays an important role in the treatment of lung cancer. Herein, we reviewed for the first time the functions and mechanisms of GRP78 in the pathological processes of lung cancer, including tumorigenesis, apoptosis, autophagy, progression, and drug resistance, giving a comprehensive understanding of the function of GRP78 in lung cancer. In addition, we also discussed the potential role of GRP78 as a prognostic biomarker and therapeutic target for lung cancer, which is conducive to improving the assessment of lung cancer and the development of new therapeutic interventions.
Inhibition of EZH2 by chidamide exerts antileukemia activity and increases chemosensitivity through Smo/Gli-1 pathway in acute myeloid leukemia
Authors: Jiang Xuejie , Jiang Ling , Cheng Jiaying , Chen Fang , Ni Jinle , Yin Changxin , Wang Qiang , Wang Zhixiang , Fang Dan , Yi Zhengshan , Yu Guopan , Zhong Qingxiu , Carter Bing Z. , Meng Fanyi
Published: March 2021

Background

Epigenetic dysregulation plays important roles in leukemogenesis and the progression of acute myeloid leukemia (AML). Histone acetyltransferases (HATs) and histone deacetylases (HDACs) reciprocally regulate the acetylation and deacetylation of nuclear histones. Aberrant activation of HDACs results in uncontrolled proliferation and blockade of differentiation, and HDAC inhibition has been investigated as epigenetic therapeutic strategy against AML.

Methods

Cell growth was assessed with CCK-8 assay, and apoptosis was evaluated by flow cytometry in AML cell lines and CD45 + and CD34 + CD38- cells from patient samples after staining with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI). EZH2 was silenced with short hairpin RNA (shRNA) or overexpressed by lentiviral transfection. Changes in signaling pathways were detected by western blotting. The effect of chidamide or EZH2-specific shRNA (shEZH2) in combination with adriamycin was studied in vivo in leukemia-bearing nude mouse models.

Results

In this study, we investigated the antileukemia effects of HDAC inhibitor chidamide and its combinatorial activity with cytotoxic agent adriamycin in AML cells. We demonstrated that chidamide suppressed the levels of EZH2, H3K27me3 and DNMT3A, exerted potential antileukemia activity and increased the sensitivity to adriamycin through disruption of Smo/Gli-1 pathway and downstream signaling target p-AKT in AML cells and stem/progenitor cells. In addition to decreasing the levels of H3K27me3 and DNMT3A, inhibition of EZH2 either pharmacologically by chidamide or genetically by shEZH2 suppressed the activity of Smo/Gli-1 pathway and increased the antileukemia activity of adriamycin against AML in vitro and in vivo.

Conclusions

Inhibition of EZH2 by chidamide has antileukemia activity and increases the chemosensitivity to adriamycin through Smo/Gli-1 pathway in AML cells (Fig. 5). These findings support the rational combination of HDAC inhibitors and chemotherapy for the treatment of AML.
Intranasal delivery of plasmids expressing bovine herpesvirus 1 gB/gC/gD proteins by polyethyleneimine magnetic beads activates long-term immune responses in mice
Authors: Liu Xing-Bo , Yu Guo-Wei , Gao Xin-Yu , Huang Jin-Long , Qin Li-Ting , Ni Hong-Bo , Lyu Chuang
Published: March 2021

Background

DNA vaccine is one of the research hotspots in veterinary vaccine development. Several advantages, such as cost-effectiveness, ease of design and production, good biocompatibility of plasmid DNA, attractive biosafety, and DNA stability, are found in DNA vaccines.

Methods

In this study, the plasmids expressing bovine herpesvirus 1 (BoHV-1) gB, gC, and gD proteins were mixed at the same mass ratio and adsorbed polyethyleneimine (PEI) magnetic beads with a diameter of 50 nm. Further, the plasmid and PEI magnetic bead polymers were packaged into double carboxyl polyethylene glycol (PEG) 600 to use as a DNA vaccine. The prepared DNA vaccine was employed to vaccinate mice via the intranasal route. The immune responses were evaluated in mice after vaccination.

Results

The expression of viral proteins could be largely detected in the lung and rarely in the spleen of mice subjected to a vaccination. The examination of biochemical indicators, anal temperature, and histology indicated that the DNA vaccine was safe in vivo. However, short-time toxicity was observed. The total antibody detected with ELISA in vaccinated mice showed a higher level than PBS, DNA, PEI + DNA, and PBS groups. The antibody level was significantly elevated at the 15th week and started to decrease since the 17th week. The neutralizing antibody titer was significantly higher in DNA vaccine than naked DNA vaccinated animals. The total IgA level was much greater in the DNA vaccine group compared to other component vaccinated groups. The examination of cellular cytokines and the percentage of CD4/CD8 indicated that the prepared DNA vaccine induced a strong cellular immunity.

Conclusion

The mixed application of plasmids expressing BoHV-1 gB/gC/gD proteins by nano-carrier through intranasal route could effectively activate long-term humoral, cellular, and mucosal immune responses at high levels in mice. These data indicate PEI magnetic beads combining with PEG600 are an efficient vector for plasmid DNA to deliver intranasally as a DNA vaccine candidate.
NTCP modeling and dose–volume correlations for acute xerostomia and dry eye after whole brain radiation
Authors: Mavroidis Panayiotis , Pearlstein Kevin A. , Moon Dominic H. , Xu Victoria , Royce Trevor J. , Weiner Ashley A. , Shen Colette J. , Marks Lawrence B. , Chera Bhishamjit S. , Das Shiva K. , Wang Kyle
Published: March 2021

Background

Whole brain radiation (WBRT) may lead to acute xerostomia and dry eye from incidental parotid and lacrimal exposure, respectively. We performed a prospective observational study to assess the incidence/severity of this toxicity. We herein perform a secondary analysis relating parotid and lacrimal dosimetric parameters to normal tissue complication probability (NTCP) rates and associated models.

Methods

Patients received WBRT to 25–40 Gy in 10–20 fractions using 3D-conformal radiation therapy without prospective delineation of the parotids or lacrimals. Patients completed questionnaires at baseline and 1 month post-WBRT. Xerostomia was assessed using the University of Michigan xerostomia score (scored 0–100, toxicity defined as ≥ 20 pt increase) and xerostomia bother score (scored from 0 to 3, toxicity defined as ≥ 2 pt increase). Dry eye was assessed using the Subjective Evaluation of Symptom of Dryness (SESoD, scored from 0 to 4, toxicity defined as ≥ 2 pt increase). The clinical data were fitted by the Lyman–Kutcher–Burman (LKB) and Relative Seriality (RS) NTCP models.

Results

Of 55 evaluable patients, 19 (35%) had ≥ 20 point increase in xerostomia score, 11 (20%) had ≥ 2 point increase in xerostomia bother score, and 13 (24%) had ≥ 2 point increase in SESoD score. For xerostomia, parotid V10Gy–V20Gy correlated best with toxicity, with AUC 0.68 for xerostomia score and 0.69–0.71 for bother score. The values for the D50, m and n parameters of the LKB model were 22.3 Gy, 0.84 and 1.0 for xerostomia score and 28.4 Gy, 0.55 and 1.0 for bother score, respectively. The corresponding values for the D50, γ and s parameters of the RS model were 23.5 Gy, 0.28 and 0.0001 for xerostomia score and 32.0 Gy, 0.45 and 0.0001 for bother score, respectively. For dry eye, lacrimal V10Gy–V15Gy were found to correlate best with toxicity, with AUC values from 0.67 to 0.68. The parameter values of the LKB model were 53.5 Gy, 0.74 and 1.0, whereas of the RS model were 54.0 Gy, 0.37 and 0.0001, respectively.

Conclusions

Xerostomia was most associated with parotid V10Gy–V20Gy, and dry eye with lacrimal V10Gy–V15Gy. NTCP models were successfully created for both toxicities and may help clinicians refine dosimetric goals and assess levels of risk in patients receiving palliative WBRT.
Correlation of [18F] FDG-PET/CT with dosimetry data: recurrence pattern after radiotherapy for head and neck carcinoma
Authors: Pisani C. , Vigna L. , Mastroleo F. , Loi G. , Amisano V. , Masini L. , Deantonio L. , Aluffi Valletti P. , Sacchetti G. , Krengli M.
Published: March 2021

Objective

To analyze the pattern of failure in relation to pre-treatment [18F] FDG-PET/CT uptake in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radio-chemotherapy (RT-CHT).

Methods and materials

From 2012 to 2016, 87 HNSCC patients treated with definitive RT-CHT, with intensity modulated radiation therapy with simultaneous integrated boost, underwent pre-treatment [18F] FDG-PET/CT (PETpre), and MRI/CT for radiotherapy (RT) planning purposes. Patients with local recurrence, received [18F] FDG-PET/CT, (PETrec) at the time of the discovery of recurrence. In these patients, the metabolic target volume (MTV), MTVpre and MTVrec were segmented on PET images by means of an adaptive thresholding algorithm. The overlapping volume between MTVpre and MTVrec (MTVpre&rec) was generated and the dose coverage of MTVrec and MTVpre&rec was checked on the planning CT using the D99 and D95 dose metrics. The recurrent volume was defined as: ‘‘In-Field (IF)’’, “Marginal recurrence” or ‘‘Out-of-Field (OF)’’ if D95 was respectively equal or higher than 95%, D95 was between 95 and 20% or the D95 was less than 20% of prescribed dose.

Results

We found 10/87 patients (11.5%) who had recurrence at primary site. Mean MTVpre was 12.2 cc (4.6–28.9 cc), while the mean MTVrec was 4.3 cc (1.1–12.7 cc). Two recurrences resulted 100% inside MTVpre, 4 recurrences were mostly inside (61–91%) and 4 recurrences were marginal to MTVpre (1–33%). At dosimetric analysis, five recurrences (50%) were IF, 4 (40%) marginal and one (10%) OF. The mean D99 of the overlapping volumes MTVpre&rec was 68.1 Gy (66.5–69.2 Gy), considering a prescription dose of 70 Gy to the planning target volume (PTV).

Conclusion

Our study shows that the recurrence may originate from the volume with the highest FDG-signal. Tumor relapse in the high-dose volume support the hypothesis that an intensification of the dose on these volumes could be further assessed to prevent local relapse.
A case of vestibular schwannoma mimicking burning mouth syndrome
Authors: Suga Takayuki , Takenoshita Miho , Tu Trang T. H. , Sugawara Takashi , Kirimura Susumu , Toyofuku Akira
Published: March 2021

Background

An oral burning sensation with unidentified cause in patients with preexisting psychosocial conditions is usually diagnosed as burning mouth syndrome. However, unexpected organic lesions may be detected in rare cases.

Case presentation

A 35-year-old woman had chief complaints of a burning sensation and numbness of the right side of the lip and tongue, as well as a dry sensation of the mouth with a taste disturbance of the right side of the tongue. The symptoms were continuous and did not show any daily fluctuations. The symptoms started without any recognizable triggering factor six months before her first visit to our clinic,. No abnormality was detected in her mouth. MRI images revealed an approximately 30 × 30 mm well-defined mass localized in the right cerebropontine angle compressing the trigeminal nerve, which was diagnosed as schwannoma of the right auditory nerve.

Conclusions

It is important for clinicians to consider the possibility of brain tumors in their differential diagnosis of BMS. Although it is not always easy to eliminate all diseases that may cause an oral burning sensation in patients with BMS-like symptoms, more attention and careful examination based on the patient’s psychosomatic background features and other possible causes are needed to rule out organic diseases.
The effect of silica desiccation under different storage conditions on filter-immobilized environmental DNA
Authors: Allison Michael J. , Round Jessica M. , Bergman Lauren C. , Mirabzadeh Ali , Allen Heather , Weir Aron , Helbing Caren C.
Published: March 2021

Objective

Silica gel beads have promise as a non-toxic, cost-effective, portable method for storing environmental DNA (eDNA) immobilized on filter membranes. Consequently, many ecological surveys are turning to silica bead filter desiccation rather than ethanol preservation. However, no systematic evaluation of silica bead storage conditions or duration past 1 week has been published. The present study evaluates the quality of filter-immobilized eDNA desiccated with silica gel under different storage conditions for over a year using targeted quantitative real-time polymerase chain reaction (qPCR)-based assays.

Results

While the detection of relatively abundant eDNA target was stable over 15 months from either ethanol- or silica gel-preserved filters at − 20 and 4 °C, silica gel out-performed ethanol preservation at 23 °C by preventing a progressive decrease in eDNA sample quality. Silica gel filter desiccation preserved low abundance eDNA equally well up to 1 month regardless of storage temperature (18, 4, or − 20 °C). However only storage at − 20 °C prevented a noticeable decrease in detectability at 5 and 12 months. The results indicate that brief storage of eDNA filters with silica gel beads up to 1 month can be successfully accomplished at a range of temperatures. However, longer-term storage should be at − 20 °C to maximize sample integrity.
Tackling tumor microenvironment through epigenetic tools to improve cancer immunotherapy
Authors: Lodewijk Iris , Nunes Sandra P. , Henrique Rui , Jerónimo Carmen , Dueñas Marta , Paramio Jesús M.
Published: March 2021

Background

Epigenetic alterations are known contributors to cancer development and aggressiveness. Additional to alterations in cancer cells, aberrant epigenetic marks are present in cells of the tumor microenvironment, including lymphocytes and tumor-associated macrophages, which are often overlooked but known to be a contributing factor to a favorable environment for tumor growth. Therefore, the main aim of this review is to give an overview of the epigenetic alterations affecting immune cells in the tumor microenvironment to provoke an immunosuppressive function and contribute to cancer development. Moreover, immunotherapy is briefly discussed in the context of epigenetics, describing both its combination with epigenetic drugs and the need for epigenetic biomarkers to predict response to immune checkpoint blockage.

Main body

Combining both topics, epigenetic machinery plays a central role in generating an immunosuppressive environment for cancer growth, which creates a barrier for immunotherapy to be successful. Furthermore, epigenetic-directed compounds may not only affect cancer cells but also immune cells in the tumor microenvironment, which could be beneficial for the clinical response to immunotherapy.

Conclusion

Thus, modulating epigenetics in combination with immunotherapy might be a promising therapeutic option to improve the success of this therapy. Further studies are necessary to (1) understand in depth the impact of the epigenetic machinery in the tumor microenvironment; (2) how the epigenetic machinery can be modulated according to tumor type to increase response to immunotherapy and (3) find reliable biomarkers for a better selection of patients eligible to immunotherapy.
Allogeneic human neural stem cells for improved therapeutic delivery to peritoneal ovarian cancer
Authors: Mooney Rachael , Abidi Wafa , Batalla-Covello Jennifer , Ngai Hoi Wa , Hyde Caitlyn , Machado Diana , Abdul-Majid Asma , Kang Yanan , Hammad Mohamed , Flores Linda , Copeland Greg , Dellinger Thanh , Han Ernest , Berlin Jacob , Aboody Karen S.
Published: March 2021

Background

Immortalized, clonal HB1.F3.CD21 human neural stem/progenitor cells (NSCs), loaded with therapeutic cargo prior to intraperitoneal (IP) injection, have been shown to improve the delivery and efficacy of therapeutic agents in pre-clinical models of stage III ovarian cancer. In previous studies, the distribution and efficacy of the NSC-delivered cargo has been examined; however, the fate of the NSCs has not yet been explored.

Methods

To monitor NSC tropism, we used an unconventional method of quantifying endocytosed gold nanorods to overcome the weaknesses of existing cell-tracking technologies.

Results

Here, we report efficient tumor tropism of HB1.F3.CD21 NSCs, showing that they primarily distribute to the tumor stroma surrounding individual tumor foci within 3 h after injection, reaching up to 95% of IP metastases without localizing to healthy tissue. Furthermore, we demonstrate that these NSCs are non-tumorigenic and non-immunogenic within the peritoneal setting.

Conclusions

Their efficient tropism, combined with their promising clinical safety features and potential for cost-effective scale-up, positions this NSC line as a practical, off-the-shelf platform to improve the delivery of a myriad of peritoneal cancer therapeutics.
Spheres of legislation: polarization and most influential nodes in behavioral context
Authors: Phillips Andrew C. , Irfan Mohammad T. , Ostertag-Hill Luca
Published: March 2021

Game-theoretic models of influence in networks often assume the network structure to be static. In this paper, we allow the network structure to vary according to the underlying behavioral context. This leads to several interesting questions on two fronts. First, how do we identify different contexts and learn the corresponding network structures using real-world data? We focus on the U.S. Senate and apply unsupervised machine learning techniques, such as fuzzy clustering algorithms and generative models, to identify spheres of legislation as context and learn an influence network for each sphere. Second, how do we analyze these networks to gain an insight into the role played by the spheres of legislation in various interesting constructs like polarization and most influential nodes? To this end, we apply both game-theoretic and social network analysis techniques. In particular, we show that game-theoretic notion of most influential nodes brings out the strategic aspects of interactions like bipartisan grouping, which structural centrality measures fail to capture.
Prior context influences motor brain areas in an auditory oddball task and prefrontal cortex multitasking modelling
Authors: Mugruza-Vassallo Carlos A. , Potter Douglas D. , Tsiora Stamatina , Macfarlane Jennifer A. , Maxwell Adele
Published: March 2021

In this study, the relationship of orienting of attention, motor control and the Stimulus- (SDN) and Goal-Driven Networks (GDN) was explored through an innovative method for fMRI analysis considering all voxels in four experimental conditions: standard target (Goal; G), novel (N), neutral (Z) and noisy target (NG). First, average reaction times (RTs) for each condition were calculated. In the second-level analysis, ‘distracted’ participants, as indicated by slower RTs, evoked brain activations and differences in both hemispheres’ neural networks for selective attention, while the participants, as a whole, demonstrated mainly left cortical and subcortical activations. A context analysis was run in the behaviourally distracted participant group contrasting the trials immediately prior to the G trials, namely one of the Z, N or NG conditions, i.e. Z.G, N.G, NG.G. Results showed different prefrontal activations dependent on prior context in the auditory modality, recruiting between 1 to 10 prefrontal areas. The higher the motor response and influence of the previous novel stimulus, the more prefrontal areas were engaged, which extends the findings of hierarchical studies of prefrontal control of attention and better explains how auditory processing interferes with movement. Also, the current study addressed how subcortical loops and models of previous motor response affected the signal processing of the novel stimulus, when this was presented laterally or simultaneously with the target. This multitasking model could enhance our understanding on how an auditory stimulus is affecting motor responses in a way that is self-induced, by taking into account prior context, as demonstrated in the standard condition and as supported by Pulvinar activations complementing visual findings. Moreover, current BCI works address some multimodal stimulus-driven systems.
Provider perspectives on beta-lactam therapeutic drug monitoring programs in the critically ill: a protocol for a multicenter mixed-methods study
Authors: Barreto Erin F. , Rule Andrew D. , Alshaer Mohammad H. , Roberts Jason A. , Abdul Aziz Mohd Hafiz , Scheetz Marc H. , Mara Kristin C. , Jannetto Paul J. , Gajic Ognjen , O’Horo John C. , Boehmer Kasey R.
Published: March 2021

Background

Beta-lactams (i.e., penicillins, cephalosporins, carbapenems, monobactams) are the most widely used class of antibiotics in critically ill patients. There is substantial interpatient variability in beta-lactam pharmacokinetics which renders their effectiveness and safety largely unpredictable. One strategy to ensure achievement of therapeutic concentrations is drug level testing (“therapeutic drug monitoring”; TDM). While studies have suggested promise with beta-lactam TDM, it is not yet widely available or implemented. This protocol presents a mixed-methods study designed to examine healthcare practitioners’ perspectives on the use and implementation of beta-lactam TDM in the critically ill.

Methods

An explanatory sequential mixed-methods design will be used [QUANT → qual]. First, quantitative data will be collected through a web-based questionnaire directed at clinicians at three academic medical centers at different phases of beta-lactam TDM implementation (not yet implemented, partially implemented, fully implemented). The sampling frame will include providers from a variety of disciplines that interact with drug level testing and interpretation in the critical care environment including pharmacists, intensivists, infectious diseases experts, medical/surgical trainees, and advanced practice providers. Second, approximately 30 individuals will be purposively sampled from survey respondents to conduct in-depth qualitative interviews to explain and expand upon the results from the quantitative strand. Normalization Process Theory and the Consolidated Framework for Implementation Science will be used to guide data analysis.

Discussion

These data will be used to answer two specific questions: “What are ICU practitioners’ perspectives on implementing beta-lactam TDM?” and “What factors contribute to the success of beta-lactam TDM program implementation?” Results of this study will be used to design future implementation strategies for beta-lactam TDM programs in the critically ill.

Trial registration

NCT04755777.
“Feeling-Seeing” inTransparent
Authors: Ripley AJ
Published: March 2021

This article explores how Jill Soloway uses mirror imagery in the series Transparent to facilitate their version of the female gaze, particularly the tenet of feeling-seeing. By doing so, this article aims to assist ongoing efforts in both transgender studies and media studies research to stretch beyond the in/visibility debate surrounding transgender representation in popular media. It proposes that Soloway’s creative process designates open, imaginative space for audiences (both cisgender and transgender alike) to witness how gender comes to matter for Maura, both in the sense of materializing in bodily form and in a manner of meaning, and how gender also comes to re-matter for her, but perhaps also for audiences watching her transformation.