bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut microbiota accelerates cisplatin-induced acute liver injury associated with robust inflammation and oxidative stress in mice
Authors: Gong Shenhai , Feng Yinglin , Zeng Yunong , Zhang Huanrui , Pan Meiping , He Fangjie , Wu Rong , Chen Jingrui , Lu Jiuling , Zhang Siyou , Yuan Songhua , Chen Xia
Published: April 2021

Background

Gut microbiota has been reported to be disrupted by cisplatin, as well as to modulate chemotherapy toxicity. However, the precise role of intestinal microbiota in the pathogenesis of cisplatin hepatotoxicity remains unknown.

Methods

We compared the composition and function of gut microbiota between mice treated with and without cisplatin using 16S rRNA gene sequencing and via metabolomic analysis. For understanding the causative relationship between gut dysbiosis and cisplatin hepatotoxicity, antibiotics were administered to deplete gut microbiota and faecal microbiota transplantation (FMT) was performed before cisplatin treatment.

Results

16S rRNA gene sequencing and metabolomic analysis showed that cisplatin administration caused gut microbiota dysbiosis in mice. Gut microbiota ablation by antibiotic exposure protected against the hepatotoxicity induced by cisplatin. Interestingly, mice treated with antibiotics dampened the mitogen-activated protein kinase pathway activation and promoted nuclear factor erythroid 2-related factor 2 nuclear translocation, resulting in decreased levels of both inflammation and oxidative stress in the liver. FMT also confirmed the role of microbiota in individual susceptibility to cisplatin-induced hepatotoxicity.

Conclusions

This study elucidated the mechanism by which gut microbiota mediates cisplatin hepatotoxicity through enhanced inflammatory response and oxidative stress. This knowledge may help develop novel therapeutic approaches that involve targeting the composition and metabolites of microbiota.
Downregulation of metallothionein-2 contributes to oxaliplatin-induced neuropathic pain
Authors: Huang Xuelin , Deng Jie , Xu Ting , Xin Wenjun , Zhang Yuehong , Ruan Xiangcai
Published: April 2021

Background

We previously reported a correlation between small doses of oxaliplatin penetrating onto the spinal cord and acute pain after chemotherapy. Here, we propose that MT2 within the spinal dorsal horns participates in the development of oxaliplatin-induced neuropathic pain and may be a pharmacological target for the prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN).

Methods

The rat model of CIPN was established by 5 consecutive injections of oxaliplatin (0.4 mg/100 g/day). Genetic restoration of neuron-specific metallothionein-2 was implemented 21 days before oxaliplatin treatment, and also, genetic inhibition by metallothionein-2 siRNA was performed. Mechanical allodynia and locomotor activity were assayed. Cell-specific expression of metallothionein-2, the mRNA levels of pro-inflammatory cytokines, nuclear translocation of NF-κB, the protein levels of expression of IκB-α, and interaction between IκB-α and P65 were evaluated in the spinal dorsal horns. Also, in vitro interaction of sequentially deleted IκB-α promoter with metallothionein-2 was used to assess the signal transduction mechanism.

Results

We found that oxaliplatin induced downregulation of metallothionein-2 in rat spinal cord neurons. By contrast, genetic restoration of metallothionein-2 in the spinal dorsal horn neuron blocked and reversed neuropathic pain in oxaliplatin-treated rats of both sexes, whereas genetic inhibition of metallothionein-2 triggered neuropathic pain in normal rats. Overall locomotor activity was not impaired after the genetic alterations of metallothionein-2. At the molecular level, metallothionein-2 modulated oxaliplatin-induced neuroinflammation, activation of NF-κB, and inactive transcriptional expression of IκB-α promoter, and these processes could be blocked by genetic restoration of metallothionein-2 in the spinal dorsal horn neurons.

Conclusions

Metallothionein-2 is a potential target for the prevention and treatment of CIPN. A reduction of NF-κB activation and inflammatory responses by enhancing the transcription of IκB-α promoter is proposed in the mechanism.
Reference values for intracranial pressure and lumbar cerebrospinal fluid pressure: a systematic review
Authors: Norager Nicolas Hernandez , Olsen Markus Harboe , Pedersen Sarah Hornshoej , Riedel Casper Schwartz , Czosnyka Marek , Juhler Marianne
Published: April 2021

Background

Although widely used in the evaluation of the diseased, normal intracranial pressure and lumbar cerebrospinal fluid pressure remain sparsely documented. Intracranial pressure is different from lumbar cerebrospinal fluid pressure. In addition, intracranial pressure differs considerably according to the body position of the patient. Despite this, the current reference values do not distinguish between intracranial and lumbar cerebrospinal fluid pressures, and body position-dependent reference values do not exist. In this study, we aim to establish these reference values.

Method

A systematic search was conducted in MEDLINE, EMBASE, CENTRAL, and Web of Sciences. Methodological quality was assessed using an amended version of the Joanna Briggs Quality Appraisal Checklist. Intracranial pressure and lumbar cerebrospinal fluid pressure were independently evaluated and subdivided into body positions. Quantitative data were presented with mean ± SD, and 90% reference intervals.

Results

Thirty-six studies were included. Nine studies reported values for intracranial pressure, while 27 reported values for the lumbar cerebrospinal fluid pressure. Reference values for intracranial pressure were −  5.9 to 8.3 mmHg in the upright position and 0.9 to 16.3 mmHg in the supine position. Reference values for lumbar cerebrospinal fluid pressure were 7.2 to 16.8 mmHg and 5.7 to 15.5 mmHg in the lateral recumbent position and supine position, respectively.

Conclusions

This systematic review is the first to provide position-dependent reference values for intracranial pressure and lumbar cerebrospinal fluid pressure. Clinically applicable reference values for normal lumbar cerebrospinal fluid pressure were established, and are in accordance with previously used reference values. For intracranial pressure, this study strongly emphasizes the scarcity of normal pressure measures, and highlights the need for further research on the matter.
Risk factors for radiation pneumonitis in lung cancer patients with subclinical interstitial lung disease after thoracic radiation therapy
Authors: Li Fangjuan , Liu Hui , Wu Hongyu , Liang Shixiong , Xu Yaping
Published: April 2021

Background

Previous studies have found that patients with subclinical interstitial lung disease (ILD) are highly susceptible to developing radiation pneumonitis (RP) after thoracic radiation therapy. In the present study we aimed to evaluate the incidence of and risk factors for RP after thoracic intensity-modulated radiation therapy in lung cancer patients with subclinical ILD.

Methods

We retrospectively analyzed data from lung cancer patients with subclinical ILD who were treated with thoracic intensity-modulated radiation therapy with a prescribed dose of ≥ 50 Gy in our institution between January 2016 and December 2017.

Results

Eighty-seven consecutive lung cancer patients with subclinical ILD were selected for the study. The median follow-up period was 14.0 months. The cumulative incidence of grades ≥ 2 and ≥ 3 RP at one year was 51.0% and 20.9%, respectively. In the multivariate analysis, a mean lung dose ≥ 12 Gy was a significant risk factor for grade ≥ 2 RP (p = 0.049). Chemotherapy with gemcitabine in the past, V5 ≥ 50%, and subclinical ILD involving ≥ 25% of the lung volume were significantly associated with grade ≥ 3 RP (p = 0.046, p = 0.040, and p = 0.024, respectively).

Conclusion

Mean lung dose is a significant risk factor for grade ≥ 2 RP. Lung cancer patients who have received chemotherapy with gemcitabine in the past, V5 ≥ 50%, and those with subclinical ILD involving ≥ 25% of lung volume have an increased risk of grade ≥ 3 RP in lung cancer patients with subclinical ILD.
Conversion and validation of rectal constraints for prostate carcinoma receiving hypofractionated carbon-ion radiotherapy with a local effect model
Authors: Wang Weiwei , Li Ping , Sheng Yinxiangzi , Huang Zhijie , Zhao Jingfang , Hong Zhengshan , Shahnazi Kambiz , Jiang Guo-Liang , Zhang Qing
Published: April 2021

Background

The study objective was to establish the local effect model (LEM) rectum constraints for 12-, 8-, and 4-fraction carbon-ion radiotherapy (CIRT) in patients with localized prostate carcinoma (PCA) using microdosimetric kinetic model (MKM)-defined and LEM-defined constraints for 16-fraction CIRT.

Methods

We analyzed 40 patients with PCA who received 16- or 12-fraction CIRT at our center. Linear-quadratic (LQ) and RBE-conversion models were employed to convert the constraints into various fractionations and biophysical models. Based on them, the MKM LQ strategy converted MKM rectum constraints for 16-fraction CIRT to 12-, 8-, and 4-fraction CIRT using the LQ model. Then, MKM constraints were converted to LEM using the RBE-conversion model. Meanwhile the LEM LQ strategy converted MKM rectum constraints for 16-fraction CIRT to LEM using the RBE-conversion model. Then, LEM constraints were converted from 16-fraction constraints to the rectum constraints for 12-, 8-, and 4-fraction CIRT using the LQ model. The LEM constraints for 16- and 12-fraction CIRT were evaluated using rectum doses and clinical follow-up. To adapt them for the MKM LQ strategy, CNAO LEM constraints were first converted to MKM constraints using the RBE-conversion model.

Results

The NIRS (i.e. DMKM|v, V-20%, 10%, 5%, and 0%) and CNAO rectum constraints (i.e. DLEM|v, V-10 cc, 5 cc, and 1 cc) were converted for 12-fraction CIRT using the MKM LQ strategy to LEM 37.60, 49.74, 55.27, and 58.01 Gy (RBE), and 45.97, 51.70, and 55.97 Gy (RBE), and using the LEM LQ strategy to 39.55, 53.08, 58.91, and 61.73 Gy (RBE), and 49.14, 55.30, and 59.69 Gy (RBE). We also established LEM constraints for 8- and 4-fraction CIRT. The 10-patient RBE-conversion model was comparable to 30-patient model. Eight patients who received 16-fraction CIRT exceeded the corresponding rectum constraints; the others were within the constraints. After a median follow-up of 10.8 months (7.1–20.8), No ≥ G1 late rectum toxicities were observed.

Conclusions

The LEM rectum constraints from the MKM LQ strategy were more conservative and might serve as the reference for hypofractionated CIRT. However, Long-term follow-up plus additional patients is necessary.
Novel hybrid treatment for extensive aortic arch aneurysms, a case report
Authors: Li Mixia , Piao Hulin , Wang Yong , Liu Kexiang
Published: April 2021

Background

The treatment for extensive aortic arch aneurysms involving the aortic arch and descending aorta is challenging for most cardiovascular surgeons. The surgical treatment is associated with a very high mortality rate. The optimal treatment has not been defined.

Case presentation

A 49-year-old male was hospitalized due to chest and upper back pain. Computed tomography angiography (CTA) demonstrated there was an extensive aortic arch aneurysm extending to the left common carotid artery and descending aorta. A novel single- stage hybrid surgery was performed on the patient through two steps: treatment of the aortic arch through median sternotomy and thoracic endovascular artery repair. The patient recovered uneventfully.

Conclusions

Our single-stage hybrid repair approach is safe, simple and effective. It provides an alternative treatment for extensive aortic arch aneurysms.
Most patient conditions do not a priori debilitate the sensitivity of thoracic ultrasound in thoracic surgery-a prospective comparative study
Authors: Galetin Thomas , Merres Julika , Schieren Mark , Marks Benjamin , Haffke Yves , Defosse Jerome , Wappler Frank , Koryllos Aris , Stoelben Erich
Published: April 2021

Background

The few existing studies on the accuracy of lung ultrasound in the detection of a postoperative pneumothorax after thoracic surgery differ in the sonographic technique and the inclusion criteria. Several conditions are considered unfavourable in the sonographic examination of the lung. We aim to test these conditions for their impact on the diagnostic accuracy of lung ultrasound.

Methods

We compared lung ultrasound and chest roentgenograms for the detection of a pneumothorax after lung-resecting surgery in two prospective trials (register ID DRKS00014557 and DRKS00020216). The ultrasound examiners and radiologists were blinded towards the corresponding findings. We performed posthoc subgroup analyses to determine the influence of various patient or surgery related conditions on the sensitivity and specificity of ultrasound in the detection of pneumothorax.

Results

We performed 340 examinations in 208 patients. The covariates were age, gender, body mass index, smoking status, severity of chronic obstructive pulmonary disease, previous ipsilateral operation or irradiation, thoracotomy, postoperative skin emphysema, indwelling chest tube and X-ray in supine position. In univariate analysis, an indwelling chest-tube was associated with a higher sensitivity (58%, p = 0.04), and a postoperative subcutaneous emphysema with a lower specificity (73% vs. 88%, p = 0.02). None of the other subgroups differed in sensitivity or specificity from the total population .

Conclusions

Most of the patient- or surgery related conditions usually considered unfavourable for lung ultrasound did not impair the sensitivity or specificity of lung ultrasound. Further studies should not excluce patients with these conditions, but test the accuracy under routine conditions.

Trial registration

DRKS, DRKS00014557, registered 06/09/2018, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00014557 and DRKS00020216, registered 03/12/2019, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020216
Modified commando procedure in complicated infective endocarditis ─ a case series
Authors: Chen Posung , Chang Chungyi , Chuang Yicheng , Chen Ichen , Lin Tingchao
Published: April 2021

Background

Complicated infective endocarditis (IE) with perivalvular abscess and destruction of intervalvular fibrous body (IFB) has high mortality risk and requires emergent or urgent surgery mostly.

Case presentation

We presented four patients with complicated infective endocarditis combined with perivalvular abscess and IFB destruction. Three patients had prosthetic valve endocarditis and one patient had native valve endocarditis. They all received modified Commando procedure successfully. No surgical mortality or re-exploration for bleeding.

Conclusions

We suggest that modified Commando procedure may have some benefit in improving survival rate of patients with complicated IE and reducing complications.
Cost-of-illness studies in rare diseases: a scoping review
Authors: García-Pérez Lidia , Linertová Renata , Valcárcel-Nazco Cristina , Posada Manuel , Gorostiza Inigo , Serrano-Aguilar Pedro
Published: April 2021

Objective

The aim of this scoping review was to overview the cost-of-illness studies conducted in rare diseases.

Methods

We searched papers published in English in PubMed from January 2007 to December 2018. We selected cost-of-illness studies on rare diseases defined as those with prevalence lower than 5 per 10,000 cases. Studies were selected by one researcher and verified by a second researcher. Methodological characteristics were extracted to develop a narrative synthesis.

Results

We included 63 cost-of-illness studies on 42 rare diseases conducted in 25 countries, and 9 systematic reviews. Most studies (94%) adopted a prevalence-based estimation, where the predominant design was cross-sectional with a bottom-up approach. Only four studies adopted an incidence-based estimation. Most studies used questionnaires to patients or caregivers to collect resource utilisation data (67%) although an important number of studies used databases or registries as a source of data (48%). Costs of lost productivity, non-medical costs and informal care costs were included in 68%, 60% and 43% of studies, respectively.

Conclusion

This review found a paucity of cost-of-illness studies in rare diseases. However, the analysis shows that the cost-of-illness studies of rare diseases are feasible, although the main issue is the lack of primary and/or aggregated data that often prevents a reliable estimation of the economic burden.
Negative drift of sedation depth in critically ill patients receiving constant minimum alveolar concentration of isoflurane, sevoflurane, or desflurane: a randomized controlled trial
Authors: Georgevici Adrian-Iustin , Kyprianou Theodoros , Herzog-Niescery Jennifer , Procopiuc Livia , Loganathan Sivakkanan , Weber Thomas Peter , Bellgardt Martin
Published: April 2021

Background

Intensive care unit (ICU) physicians have extended the minimum alveolar concentration (MAC) to deliver and monitor long-term volatile sedation in critically ill patients. There is limited evidence of MAC’s reliability in controlling sedation depth in this setting. We hypothesized that sedation depth, measured by the electroencephalography (EEG)-derived Narcotrend-Index (burst-suppression N_Index 0—awake N_Index 100), might drift downward over time despite constant MAC values.

Methods

This prospective single-centre randomized clinical study was conducted at a University Hospital Surgical Intensive Care Unit and included consecutive, postoperative ICU patients fulfilling the inclusion criteria. Patients were randomly assigned to receive uninterrupted inhalational sedation with isoflurane, sevoflurane, or desflurane. The end-expiratory concentration of the anaesthetics and the EEG-derived index were measured continuously in time-stamped pairs. Sedation depth was also monitored using Richmond-Agitation-Sedation-Scale (RASS). The paired t-test and linear models (bootstrapped or multilevel) have been employed to analyze MAC,
N_Index and RASS across the three groups.

Results

Thirty patients were recruited (female/male: 10/20, age 64 ± 11, Simplified Acute Physiology Score II 30 ± 10). In the first 24 h, 21.208 pairs of data points (N_Index and MAC) were recorded. The median MAC of 0.58 ± 0.06 remained stable over the sedation time in all three groups. The t-test indicated in the isoflurane and sevoflurane groups a significant drop in RASS and EEG-derived N_Index in the first versus last two sedation hours. We applied a multilevel linear model on the entire longitudinal data, nested per patient, which produced the formula N_Index = 43 − 0.7·h (R2 = 0.76), showing a strong negative correlation between sedation’s duration and the N_Index. Bootstrapped linear models applied for each sedation group produced: N_Index of 43–0.9, 45–0.8, and 43–0.4·h for isoflurane, sevoflurane, and desflurane, respectively. The regression coefficient for desflurane was almost half of those for isoflurane and sevoflurane, indicating a less pronounced time-effect in this group.

Conclusions

Maintaining constant MAC does not guarantee stable sedation depth. Thus, the patients necessitate frequent clinical assessments or, when unfeasible, continuous EEG monitoring. The differences across different volatile anaesthetics regarding their time-dependent negative drift requires further exploration.

Trial registration: NCT03860129.
PD-L1 lncRNA splice isoform promotes lung adenocarcinoma progression via enhancing c-Myc activity
Authors: Qu Shuang , Jiao Zichen , Lu Geng , Yao Bing , Wang Ting , Rong Weiwei , Xu Jiahan , Fan Ting , Sun Xinlei , Yang Rong , Wang Jun , Yao Yongzhong , Xu Guifang , Yan Xin , Wang Tao , Liang Hongwei , Zen Ke
Published: April 2021

Background

Although using a blockade of programmed death-ligand 1 (PD-L1) to enhance T cell immune responses shows great promise in tumor immunotherapy, the immune-checkpoint inhibition strategy is limited for patients with solid tumors. The mechanism and efficacy of such immune-checkpoint inhibition strategies in solid tumors remains unclear.

Results

Employing qRT-PCR, Sanger sequencing, and RNA BaseScope analysis, we show that human lung adenocarcinoma (LUAD) all produce a long non-coding RNA isoform of PD-L1 (PD-L1-lnc) by alternative splicing, regardless if the tumor is positive or negative for the protein PD-L1. Similar to PD-L1 mRNA, PD-L1-lnc in various lung adenocarcinoma cells is significantly upregulated by IFNγ. Both in vitro and in vivo studies demonstrate that PD-L1-lnc increases proliferation and invasion but decreases apoptosis of lung adenocarcinoma cells. Mechanistically, PD-L1-lnc promotes lung adenocarcinoma progression through directly binding to c-Myc and enhancing c-Myc transcriptional activity.

Conclusions

In summary, the PD-L1 gene can generate a long non-coding RNA through alternative splicing to promote lung adenocarcinoma progression by enhancing c-Myc activity. Our results argue in favor of investigating PD-L1-lnc depletion in combination with PD-L1 blockade in lung cancer therapy.
Hdac1 and Hdac2 are essential for physiological maturation of a Cx3cr1 expressing subset of T-lymphocytes
Authors: Datta Moumita , Staszewski Ori
Published: April 2021

Objective

Histone acetylation is an important mechanism in the regulation of gene expression and plays a crucial role in both cellular development and cellular response to external or internal stimuli. One key aspect of this form of regulation is that acetylation marks can be added and removed from sites of regulation very quickly through the activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs). The activity of both HATs and HDACs has been shown to be important for both physiological hematopoiesis as well as during development of hematological neoplasia, such as lymphomas. In the present study we analyzed the effect of knockout of the two HDACs, Hdac1 and Hdac2 in cells expressing the fractalkine receptor (Cx3cr1) on lymphocyte development.

Results

We report data showing a maturation defect in mice harboring a Cx3cr1 dependent knockout of Hdac1 and 2. Furthermore, we report that these mice develop a T-cell neoplasia at about 4–5 months of age, suggesting that a Cx3cr1 expressing subpopulation of immature T-cells gives rise to T-cell lymphomas in the combined absence of Hdac1 and Hdac2.
Disparities and interventions in the timeliness of endometrial cancer diagnosis and treatment in the United States: a scoping review protocol
Authors: Najor Anna J. , Dao Dyda , Bakkum-Gamez Jamie N. , Sherman Mark E. , Connor Avonne E. , Destephano Christopher C.
Published: April 2021

Background

Disparities in the stage at diagnosis of endometrial cancer (EC) account for a significant proportion of the disparities in morbidity and mortality experienced by vulnerable groups in the USA. Evidence suggests that disparities in timeliness of care and treatment play a significant role in stage at diagnosis. Despite an increase in literature on EC disparities, the issue remains largely unchanged. The objectives of this review will be to synthesize the evidence to identify important remaining research questions and inform future interventions to reduce the disparity in stage at diagnosis of EC in the USA.

Methods

This scoping review protocol will use the five-step framework developed by Arksey and O’Malley. A literature search will be conducted from January 2000 onwards in PubMed, EMBASE, Scopus, and Cochrane CENTRAL databases. Studies on delays in care of EC will be included if they were published in English and reported findings for the US population. Two reviewers will independently screen all citations, full-text articles, and abstract data. The study methodological quality and bias will be appraised using appropriate tools. A narrative summary of findings will be conducted. Data analysis will involve quantitative (e.g., frequencies) and qualitative (e.g., content and thematic analysis) methods. The literature search, data extraction, and evidence synthesis will be informed by the Pathway to Treatment Model, which divides time to cancer care initiation into appraisal, help-seeking, diagnostic, and pre-treatment intervals. Results will be reported in accordance with the PRISMA statement.

Discussion

EC disparities research is currently benefitting form a growing expectation that studies have a real impact on disparities. Patient, healthcare, and disease factors impact the amount of time patients spend in different intervals of the Pathway to Treatment Model, so research and interventions aimed at reducing disparities in EC survival should be designed with cognizance to how these factors impact their target population. Reviews on disparities in stage at diagnosis of EC exist but do not provide a comprehensive picture of the pathway to treatment. This review will seek to provide an expanded bedrock of evidence for future studies to build on as they aim to more actively reduce EC disparities.

Trial registration

Open Science Framework (osf.io/v2zxy).
Certain new proportional and Hadamard proportional fractional integral inequalities
Authors: Rahman Gauhar , Nisar Kottakkaran Sooppy , Abdeljawad Thabet
Published: April 2021

The main goal of this paper is estimating certain new fractional integral inequalities for the extended Chebyshev functional in the sense of synchronous functions by employing proportional fractional integral (PFI) and Hadamard proportional fractional integral. We establish certain inequalities concerning one- and two-parameter proportional and Hadamard proportional fractional integrals. We also discuss certain particular cases.
A note on two-term exponential sum and the reciprocal of the quartic Gauss sums
Authors: Zhang Wenpeng , Lv Xingxing
Published: April 2021

The main purpose of this article is by using the properties of the fourth character modulo a prime p and the analytic methods to study the calculating problem of a certain hybrid power mean involving the two-term exponential sums and the reciprocal of quartic Gauss sums, and to give some interesting calculating formulae of them.
Sustainable forest biomass: a review of current residue harvesting guidelines
Authors: Titus Brian D. , Brown Kevin , Helmisaari Heljä-Sisko , Vanguelova Elena , Stupak Inge , Evans Alexander , Clarke Nicholas , Guidi Claudia , Bruckman Viktor J. , Varnagiryte-Kabasinskiene Iveta , Armolaitis Kęstutis , de Vries Wim , Hirai Keizo , Kaarakka Lilli , Hogg Karen , Reece Pam
Published: April 2021

Forest biomass harvesting guidelines help ensure the ecological sustainability of forest residue harvesting for bioenergy and bioproducts, and hence contribute to social license for a growing bioeconomy. Guidelines, typically voluntary, provide a means to achieve outcomes often required by legislation, and must address needs related to local or regional context, jurisdictional compatibility with regulations, issues of temporal and spatial scale, and incorporation of appropriate scientific information. Given this complexity, comprehensive reviews of existing guidelines can aid in development of new guidelines or revision of existing ones. We reviewed 32 guidelines covering 43 jurisdictions in the USA, Canada, Europe and East Asia to expand upon information evaluated and recommendations provided in previous guideline reviews, and compiled a searchable spreadsheet of direct quotations from documents as a foundation for our review. Guidelines were considered in the context of sustainable forest management (SFM), focusing on guideline scope and objectives, environmental sustainability concerns (soils, site productivity, biodiversity, water and carbon) and social concerns (visual aesthetics, recreation, and preservation of cultural, historical and archaeological sites). We discuss the role of guidelines within the context of other governance mechanisms such as SFM policies, trade regulations and non-state market-driven (NSMD) standards, including certification systems. The review provides a comprehensive resource for those developing guidelines, or defining sustainability standards for market access or compliance with public regulations, and/or concerned about the sustainability of forest biomass harvesting. We recommend that those developing or updating guidelines consider (i) the importance of well-defined and understood terminology, consistent where possible with guidelines in other jurisdictions or regions; (ii) guidance based on locally relevant research, and periodically updated to incorporate current knowledge and operational experience; (iii) use of indicators of sensitive soils, sites, and stands which are relevant to ecological processes and can be applied operationally; and (iv) incorporation of climate impacts, long-term soil carbon storage, and general carbon balance considerations when defining sustainable forest biomass availability. Successful implementation of guidelines depends both on the relevance of the information and on the process used to develop and communicate it; hence, appropriate stakeholders should be involved early in guideline development.
Modified PCR protocol to increase sensitivity for determination of bacterial community composition
Authors: Williamson Kayla M. , Wagner Brandie D. , Robertson Charles E. , Stevens Mark J. , Sontag Marci K. , Mourani Peter M. , Harris J. Kirk
Published: April 2021

Background

The objective of this project was to increase the sensitivity of sequence-based bacterial community determination without impacting community composition or interfering with cluster formation during sequencing. Two PCR protocols (standard and modified) were examined in airway samples where we observed a large range in bacterial load (3.1–6.2 log10 16S rRNA gene copies/reaction). Tracheal aspirate (TA) samples (n = 99) were collected from sixteen children requiring mechanical ventilation at a single center. DNA was extracted, and total bacterial load (TBL) was assessed using qPCR. Amplification of 16S rRNA was attempted with both protocols in all samples.

Results

PCR product was observed using both protocols in 52 samples and in 24 additional samples only with the modified protocol. TBL, diversity metrics, and prominent taxa were compared for samples in three groups based on success of the two protocols (successful with both, success with modified only, unsuccessful for both). TBL differed significantly across the three groups (p<0.001). Specifically, the modified protocol allowed amplification from samples with intermediate TBL. Shannon diversity was similar between the two protocols, and Morisita-Horn beta diversity index showed high agreement between the two protocols within samples (median value 0.9997, range 0.9947 to 1). We show that both protocols identify similar communities, and the technical variability of both protocols was very low. The use of limited PCR cycles was a key feature to limit impact of background by exclusion of 24% of samples with no evidence of bacterial DNA present in the sample.

Conclusion

The modified amplification protocol represents a viable approach that increased sensitivity of bacterial community analysis, which is important for study of the human airway microbiome where bacterial load is highly variable.
Microvascularized tumor organoids-on-chips: advancing preclinical drug screening with pathophysiological relevance
Authors: Lim Jungeun , Ching Hanna , Yoon Jeong-Kee , Jeon Noo Li , Kim YongTae
Published: April 2021

Recent developments of organoids engineering and organ-on-a-chip microfluidic technologies have enabled the recapitulation of the major functions and architectures of microscale human tissue, including tumor pathophysiology. Nevertheless, there remain challenges in recapitulating the complexity and heterogeneity of tumor microenvironment. The integration of these engineering technologies suggests a potential strategy to overcome the limitations in reconstituting the perfusable microvascular system of large-scale tumors conserving their key functional features. Here, we review the recent progress of in vitro tumor-on-a-chip microfluidic technologies, focusing on the reconstruction of microvascularized organoid models to suggest a better platform for personalized cancer medicine.
Acute presentation of cocoon abdomen as septic peritonitis mimicking with strangulated internal herniation: a case report
Authors: Saqib Sabah Uddin , Farooq Rimsha , Saleem Omair , Moeen Sarosh , Chawla Tabish Umer
Published: April 2021

Background

Abdominal cocoon syndrome is a rare cause of intestinal obstruction in which loops of small bowel get entrapped inside a fibro-collagenous membrane. Condition is also known in the literature as sclerosing peritonitis and in the majority of cases, it has no known cause. Although the majority of patients exhibit long-standing signs and symptoms of partial bowel obstruction in an out-patient clinic, its acute presentation in the emergency room with features of sepsis is extremely rare. This case report aims to describe the emergency presentation of cocoon abdomen with septic peritonitis.

Case presentation

A 35-year-old male with no known co-morbidity and no prior history of prior laparotomy presented in emergency room first time with a 1-day history of generalized abdomen pain, vomiting, and absolute constipation. He was in grade III shock and had metabolic acidosis. The clinical impression was of the perforated appendix, but initial contrast-enhanced computed tomography (CECT) was suggestive of strangulated internal herniation of small bowel. Emergency laparotomy after resuscitation revealed hypoperfused, but viable loops of small bowel entrapped in the sclerosing membrane. Extensive adhesiolysis and removal of the membrane were performed and the entire bowel was straightened. Postoperatively he remained well and discharged as planned. Histopathology report confirms features of sclerosing peritonitis.

Discussion

Cocoon abdomen is a very rare cause of acute small bowel obstruction presenting in an emergency with features of septic peritonitis. Condition is mostly chronic and generally mimics abdominal TB in endemic areas like India and Pakistan. A high index of suspicion is required in an emergency setting and exploratory laparotomy is diagnostic and therapeutic as well and the condition mimics internal herniation in acute cases.

Conclusion

Cocoon abdomen as a cause of septic peritonitis is extremely rare and might be an unexpected finding at laparotomy. Removal of membrane and estimation of the viability of entrapped bowel loops is the treatment of choice, which may require resection in the extreme case of gangrene.
To supervise or to self-supervise: a machine learning based comparison on credit supervision
Authors: Antunes José Américo Pereira
Published: April 2021

This study investigates the need for credit supervision as conducted by on-site banking supervisors. It builds on a real bank on-site credit examination to compare the performance of a hypothetical self-supervision approach, in which banks themselves assess their loan portfolios without external intervention, with the on-site banking supervision approach of the Central Bank of Brazil. The experiment develops two machine learning classification models: the first model is based on good and bad ratings informed by banks, and the second model is based on past on-site credit portfolio examinations conducted by banking supervision. The findings show that the overall performance of the on-site supervision approach is consistently higher than the performance of the self-supervision approach, justifying the need for on-site credit portfolio examination as conducted by the Central Bank.
Correction to: Dietary habits of patients with coronary artery disease in a tertiary-care hospital of Bangladesh: a case-controlled study
Authors: Khatun Taslima , Maqbool Dilara , Ara Ferdous , Sarker Manika Rani , Anwar Kazi Selim , Hoque Asirul
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Two people, one graph: the effect of rotated viewpoints on accessibility of data visualizations
Authors: Müller Tjark , Hesse Friedrich W. , Meyerhoff Hauke S.
Published: April 2021

In co-located, multi-user settings such as multi-touch tables, user interfaces need to be accessible from multiple viewpoints. In this project, we investigated how this goal can be achieved for depictions of data in bar graphs. We designed a laboratory task in which participants answered simple questions based on information depicted in bar graphs presented from differently rotated points of view. As the dependent variable, we measured differences in response onsets relative to the standard viewpoint (i.e., upright graphs). In Experiment 1, we manipulated graph and label orientation independently of each other. We observed that rotations of the labels rather than rotations of the graph itself pose a challenge for accessing depicted information from rotated viewpoints. In Experiment 2, we studied whether replacing word labels with pictographs could overcome the detrimental effects of rotated labels. Rotated pictographs were less detrimental than rotated word labels, but performance was still worse than in the unrotated baseline condition. In Experiment 3, we studied whether color coding could overcome the detrimental effects of rotated labels. Indeed, for multicolored labels, the detrimental effect of label rotation was in the negligible range. We discuss the implications of our findings for the underlying psychological theory as well as for the design of depicted statistical information in multi-user settings.
Rethinking and strengthening the Global Health Diplomacy through triangulated nexus between policy makers, scientists and the community in light of COVID-19 global crisis
Authors: AlKhaldi Mohammed , James Nigel , Chattu Vijay Kumar , Ahmed Sara , Meghari Hamza , Kaiser Kirsty , IJsselmuiden Carel , Tanner Marcel
Published: April 2021

The COVID-19 pandemic is considerably the biggest global health challenge of this modern era. Spreading across all regions of the world, this corona virus disease has disrupted even some of the most advanced economies and healthcare systems. With an increasing global death toll and no near end in sight, questions on the efficacy of global response mechanisms, including the role and relevancy of global health institutions, have emerged. Using a reflexive content analytic approach, this study sheds light on some of these questions, underscoring the disconnect between science, policymaking, and society. Global health funding approaches; politicization of the pandemic, including political blame gaming; mistrust of government and other institutions; and a lack of robust accountability measures are some of the pandemic response obstacles. However, COVID-19 has also presented an opportunity for a collaboration that may potentially solidify global solidarity. A pandemic response built on strategic global health diplomacy, vaccine diplomacy, and science diplomacy can spur both political and economic benefits, advancing development, health security, and justice. The virus thrives and flourishes in face of political divisions and lack of cooperation. While the current global crisis has exacerbated the existing social injustices in societies, national unity and global solidarity is essential to winning the fight against the COVID-19 pandemic.
Effect of inverse ratio ventilation on hemodynamics and respiratory mechanics in obese patients undergoing laparoscopic sleeve gastrectomy
Authors: Sayed Noha Hussein , Elaziz Mohamed Saeed Abd , Elkholy Amgad Serag , Taeimah Mohamed Osman
Published: April 2021

Background

Obesity has become a global epidemic problem affecting every system and is associated with many consequences including coronary artery disease, hypertension, diabetes mellitus, dyslipidemia, obstructive sleep apnea, and socioeconomic and psychosocial impairment. Laparoscopic sleeve gastrectomy is one of the best and most commonly done operations for weight loss. Elevated peak airway pressure and hypoxemia are common problems that anesthesiologists face during laparoscopic surgeries with conventional volume-controlled ventilation. This study aimed at the use of the prolonged I:E ratio as an alternative strategy to improve gas exchange and the respiratory mechanics of obese patients undergoing laparoscopic sleeve gastrectomy.

Results

The study was a prospective randomized controlled trial and was performed between April 2019 and March 2020. After the approval of the departmental ethical committee and the informed written consent had been taken from the patients, fifty-two obese patients undergoing laparoscopic sleeve gastrectomy were enrolled in this study. After endotracheal intubation, the patients were randomly divided into the IRV group (n=26) and the VCV group (n=26). Respiratory parameters were adjusted as tidal volume (Vt) 8mL/kg ideal body weight, respiratory rate 12 breaths/min, positive-end expiratory pressure (PEEP) 0, fractional inspired oxygen (FiO2) 0.6, and I:E ratio 1:2 for the VCV group and 2:1 for the IRV group; hemodynamics and respiratory mechanics were monitored and recorded after intubation (0 min), before pneumoperitoneum (10 mins), and after pneumoperitoneum (20 mins), 30, 40, 50, and 60 mins. IRV significantly improves the respiratory mechanics during pneumoperitoneum in the form of decreasing the peak pressure (Ppeak) and plateau pressure (Pplat) and improving the dynamic compliance, but the mean pressure (Pmean) was increased; it also increased the partial pressure of oxygen (arterial PO2) significantly. No statistical significance was found regarding the demographic data or the hemodynamics.

Conclusion

IRV is superior to conventional VCV in morbidly obese patients undergoing laparoscopic sleeve gastrectomy as it improves respiratory mechanics and oxygenation.
Anticancer natural products from Aspergillus neoniger, an endophyte of Ficus carica
Authors: Abdou Randa , Alqahtani Alaa M. , Attia Gouda H.
Published: April 2021

Background

Several plants have not been investigated for their endophytes, such as the medicinal plant Ficus carica for which anticancer activity has been confirmed. The endophyte Aspergillus neoniger was selected for investigation of its metabolites since it exerted anticancer activities in preliminary screening assays.

Results

Bioactivity-guided chromatographic fractionation was performed on the endophytic extract and resulted in the identification of asperazine and asperazine A through spectroscopic analysis. Moderate cytotoxicity against HeLa cell lines (CC50 = 18.4 µg mL−1) and moderate antiproliferative effects against HUVEC and K-562 cell lines (GI50 = 31.5 and 24.8 µg mL−1, respectively) were observed for asperazine. Asperazine A on the other hand showed weak cytotoxic activity against HeLa cell lines (CC50 = 34.6 µg mL−1) as well as weak cytostatic activities against HUVEC and K-562 cell lines (GI50 = 40.7 and 50.2 µg mL−1, respectively) while no antimicrobial activity was detected for both compounds.

Conclusions

These results suggest contribution of A. neoniger to the reported anticancer activity of the host plant and provides a new source of anticancer metabolites with therapeutic potential.
This Is a Different Patient Population: Opioid Prescribing Challenges for Patients With Cancer-Related Pain
Authors: Schenker Yael , Hamm Megan , Bulls Hailey W. , Merlin Jessica S. , Wasilko Rachel , Dawdani Alicia , Kenkre Balchandre , Belin Shane , Sabik Lindsay M.
Published: April 2021

PURPOSE:

Responses to the opioid epidemic in the United States, including efforts to monitor and limit prescriptions for noncancer pain, may be affecting patients with cancer. Oncologists' views on how the opioid epidemic may be influencing treatment of cancer-related pain are not well understood.

METHODS:

We conducted a multisite qualitative interview study with 26 oncologists from a mix of urban and rural practices in Western Pennsylvania. The interview guide asked about oncologists' views of and experiences in treating cancer-related pain in the context of the opioid epidemic. A multidisciplinary team conducted thematic analysis of interview transcripts to identify and refine themes related to challenges to safe and effective opioid prescribing for cancer-related pain and recommendations for improvement.

RESULTS:

Oncologists described three main challenges: (1) patients who receive opioids for cancer-related pain feel stigmatized by clinicians, pharmacists, and society; (2) patients with cancer-related pain fear becoming addicted, which affects their willingness to accept prescription opioids; and (3) guidelines for safe and effective opioid prescribing are often misinterpreted, leading to access issues. Suggested improvements included educational materials for patients and families, efforts to better inform prescribers and the public about safe and appropriate uses of opioids for cancer-related pain, and additional support from pain and/or palliative care specialists.

CONCLUSION:

Challenges to safe and effective opioid prescribing for cancer-related pain include opioid stigma and access barriers. Interventions that address opioid stigma and provide additional resources for clinicians navigating complex opioid prescribing guidelines may help to optimize cancer pain treatment.
Υγεία και μετανάστες
Authors: Χαραλαμπόπουλος Βασίλειος
Published: April 2021

Τις τελευταίες δεκαετίες ως αποτέλεσμα της εντεινόμενης παγκοσμιοποίησης, με την έννοια της ακόμα μεγαλύτερης σμίκρυνσης των αποστάσεων και της αποδυνάμωσης των συνοριακών ελέγχων και εμποδίων, έχει συμβεί να έχουν αυξηθεί με γεωμετρική πρόοδο μεταναστευτικές και προσφυγικές πληθυσμιακές ροές. Για την παρούσα μελέτη αφορμή στάθηκε το καθεστώς κρίσης και επείγουσας ανάγκης που δημιουργούν αυτές οι πληθυσμιακές μετακινήσεις, το οποίο επιτάθηκε τον Ιούλιο του 2015. Καθότι ίσως ποτέ στην ανθρώπινη ιστορία μέχρι σήμερα δεν έχουν συμβεί ανάλογες σε μέγεθος μετακινήσεις, στόχος της παρούσης διατριβής αποτέλεσε η μελέτης της επίπτωσης της μεταναστευτικής κρίσης στα συστήματα υγείας και τη δημόσια διοίκηση. Για το λόγο αυτό, καταγράψαμε την προσέλευση μεταναστών σε χειρουργικές κλινικές, με σημείο αναφοράς τον Ιούλιο του 2015 και συγκρίναμε τα μεγέθη. Φάνηκε πως υπήρξε αύξηση σε συγκεκριμένους τύπους επεμβάσεων και επομένως και οικονομική επιβάρυνση. Για πρώτη φορά, μία μελέτη προσπαθεί να αποσαφηνίσει την περεταίρω επιβάρυνση που προκάλεσε η έξαρση του μεταναστευτικού, στο ελληνικό σύστημα υγείας. Καταγράψαμε τη φύση των περιστατικών που προσήλθαν σε χειρουργικές κλινικές και τεκμηριώσαμε την ποιοτική μεταβολή τους. Παράλληλα -δεδομένων των αδυναμιών στα προβλήματα χρέωσης και κοστολόγησης- όχι απλά αποδείξαμε την επιβάρυνση στα οικονομικά της υγείας αλλά καταδείξαμε και ποιες επεμβάσεις ήταν εκείνες που την προκάλεσαν. Χρειάζονται επιπλέον μελέτες.