bluuebunny/crossref_metadata_2025 huggingface dataset:
Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populations
Authors: Wang Kai , Shi Xian , Zhu Ziwei , Hao Xingjie , Chen Liangkai , Cheng Shanshan , Foo Roger S. Y. , Wang Chaolong
Published: June 2022

Background

Coronary artery disease (CAD) remains the leading cause of mortality worldwide despite enormous efforts devoted to its prevention and treatment. While many genetic loci have been identified to associate with CAD, the intermediate causal risk factors and etiology have not been fully understood. This study assesses the causal effects of 37 heritable clinical factors on CAD in East Asian and European populations.

Methods

We collected genome-wide association summary statistics of 37 clinical factors from the Biobank Japan (42,793 to 191,764 participants) and the UK Biobank (314,658 to 442,817 participants), paired with summary statistics of CAD from East Asians (29,319 cases and 183,134 controls) and Europeans (91,753 cases and 311,344 controls). These clinical factors covered 12 cardiometabolic traits, 13 hematological indices, 7 hepatological and 3 renal function indices, and 2 serum electrolyte indices. We performed univariable and multivariable Mendelian randomization (MR) analyses in East Asians and Europeans separately, followed by meta-analysis.

Results

Univariable MR analyses identified reliable causal evidence (P< 0.05/37) of 10 cardiometabolic traits (height, body mass index [BMI], blood pressure, glycemic and lipid traits) and 4 other clinical factors related to red blood cells (red blood cell count [RBC], hemoglobin, hematocrit) and uric acid (UA). Interestingly, while generally consistent, we identified population heterogeneity in the causal effects of BMI and UA, with higher effect sizes in East Asians than those in Europeans. After adjusting for cardiometabolic factors in multivariable MR analysis, red blood cell traits (RBC, meta-analysis odds ratio 1.07 per standard deviation increase, 95% confidence interval 1.02–1.13; hemoglobin, 1.10, 1.03–1.16; hematocrit, 1.10, 1.04–1.17) remained significant (P< 0.05), while UA showed an independent causal effect in East Asians only (1.12, 1.06–1.19,P= 3.26×10−5).

Conclusions

We confirmed the causal effects of 10 cardiometabolic traits on CAD and identified causal risk effects of RBC, hemoglobin, hematocrit, and UA independent of traditional cardiometabolic factors. We found no causal effects for 23 clinical factors, despite their reported epidemiological associations. Our findings suggest the physiology of red blood cells and the level of UA as potential intervention targets for the prevention of CAD.
Therapeutic effects of intranasal tocotrienol-rich fraction on rhinitis symptoms in platelet-activating factor induced allergic rhinitis
Authors: Teo Cheryl Wei Ling , Png Stephanie Jia Ying , Ung Yee Wei , Yap Wei Ney
Published: June 2022

Background

Platelet-activating factor (PAF) has been suggested to be a potent inflammatory mediator in Allergic rhinitis (AR) pathogenesis. Vitamin E, an essential nutrient that comprises tocopherol and tocotrienol, is known as a potential therapeutic agent for airway allergic inflammation. This study aimed to investigate the beneficial effects of intranasal Tocotrienol-rich fraction (TRF) on PAF-induced AR in a rat model.

Methods

Sprague Dawley rats were randomly assigned into 3 groups: Control, PAF-induced AR and PAF-induced AR with TRF treatment. To induce AR, 50 μl of 16 μg/ml PAF was nasally instilled into each nostril. From day 1 to 7 after AR induction, 10 μl of 16 μg/μl TRF was delivered intranasally to the TRF treatment group. Complete upper skulls were collected for histopathological evaluation on day 8.

Results

The average severity scores of AR were significantly higher in the PAF-induced AR rats compared to both control and PAF-induced AR with TRF treatment. The histologic examination of the nasal structures showed moderate degree of inflammation and polymorphonuclear cells infiltration in the lamina propria, mucosa damage and vascular congestion in the PAF-induced AR rats. TRF was able to ameliorate the AR symptoms by restoring the nasal structures back to normal. H&E staining demonstrated a statistically significant benefit upon TRF treatment, where minimal degree of inflammation, and a reduction in the infiltration of polymorphonuclear cells, mucosa damage and vascular congestion were observed.

Conclusion

TRF exhibited symptomatic relief action in AR potentially due to its antioxidant, anti-inflammatory and anti-allergic properties.
Patient selection for milk and egg ladders using a food ladder safety checklist
Authors: Chua Gilbert T. , Chan Edmond S. , Yeung Joanne , Cameron Scott B. , Soller Lianne , Williams Brock A. , Chomyn Alanna , Vander Leek Timothy K. , Abrams Elissa M. , Mak Raymond , Wong Tiffany
Published: June 2022

A food ladder is a form of home-based dietary advancement therapy that gradually increases exposure to an allergenic food through the gradual introduction of egg or milk containing food with increasing quantity and allergenicity from extensively heated forms, such as baked goods, to less processed products. While widely considered safe, the food ladder is not risk-free and most of the egg and milk ladder studies only included preschoolers with mild egg and milk allergies, and with no or well-controlled asthma. We propose a Food Ladder Safety Checklist to assist with patient selection using “4 A's” based on available evidence for food ladders, including Age, active or poorly controlled Asthma, history of Anaphylaxis, and Adherence.
PET imaging of an optimized anti-PD-L1 probe 68Ga-NODAGA-BMS986192 in immunocompetent mice and non-human primates
Authors: Zhou Huimin , Bao Guangfa , Wang Ziqiang , Zhang Buchuan , Li Dan , Chen Lixing , Deng Xiaoyun , Yu Bo , Zhao Jun , Zhu Xiaohua
Published: June 2022

Background

Adnectin is a protein family derived from the 10th type III domain of human fibronectin (10Fn3) with high-affinity targeting capabilities. Positron emission tomography (PET) probes derived from anti-programmed death ligand-1 (PD-L1) Adnectins, including 18F- and 68Ga-labeled BMS-986192, are recently developed for the prediction of patient response to immune checkpoint blockade. The 68Ga-labeled BMS-986192, in particular, is an attractive probe for under-developed regions due to the broader availability of 68Ga. However, the pharmacokinetics and biocompatibility of 68Ga-labeled BMS-986192 are still unknown, especially in non-human primates, impeding its further clinical translation.

Methods

We developed a variant of 68Ga-labeled BMS-986192 using 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) as the radionuclide–chelator. The resultant probe, 68Ga-NODAGA-BMS986192, was evaluated in terms of targeting specificity using a bilateral mouse tumor model inoculated with wild-type B16F10 and B16F10 transduced with human PD-L1 (hPD-L1-B16F10). The dynamic biodistribution and radiation dosimetry of this probe were also investigated in non-human primate cynomolgus.

Results

68Ga-NODAGA-BMS986192 was prepared with a radiochemical purity above 99%. PET imaging with 68Ga-NODAGA-BMS986192 efficiently delineated the hPD-L1-B16F10 tumor at 1 h post-injection. The PD-L1-targeting capability of this probe was further confirmed using in vivo blocking assay and ex vivo biodistribution studies. PET dynamic imaging in both mouse and cynomolgus models revealed a rapid clearance of the probe via the renal route, which corresponded to the low background signals of the PET images. The probe also exhibited a favorable radiation dosimetry profile with a total-body effective dose of 6.34E-03 mSv/MBq in male cynomolgus.

Conclusions

68Ga-NODAGA-BMS986192 was a feasible and safe tool for the visualization of human PD-L1. Our study also provided valuable information on the potential of targeted PET imaging using Adnectin-based probes.
Mapping research evidence on implementation of the WHO ‘best buys’ and other interventions for the prevention and control of non-communicable diseases in sub-Saharan Africa: a scoping review protocol
Authors: Kadiri Adjei , Ansu-Mensah Monica , Bawontuo Vitalis , Kuupiel Desmond
Published: June 2022

Background

The rising burden of non-communicable diseases (NCDs) is a global health concern. To reduce the burden of morbidity, mortality and disability due to NCDs, the World Health Organization (WHO) developed ‘best buys’ and other interventions for the prevention and control of NCDs by member countries. However, their extent of implementation especially in sub-Saharan African countries (SSA) is not known. Therefore, this scoping review aims to map and describe research evidence on implementation of the WHO’s ‘best buys’ and other interventions for reducing unhealthy diets in SSA.

Methods

This review will be guided by the enhanced version of Arksey and O’Malley’s framework and the recent Joanna Briggs Institute guidelines for scoping reviews. To identify the relevant published literature for this review, a comprehensive keyword search will be conducted in PubMed, SCOPUS, EBSCOhost (CINAHL, Health Resource and PsycINFO) and Cochrane Library from 2017 to 2021. Boolean terms (‘AND’ and ‘OR’), as well as Medical Subject Heading terms, will be included where essential. Government websites of SSA countries, the WHO’s website and Google Scholar will be consulted for grey literature such as governmental policies/strategies focus on reducing unhealthy diets. Moreover, the reference list of included evidence sources will be searched for additional literature. Two reviewers will independently screen the articles at the abstract and full-text screening phases guided by the review eligibility criteria. Also, all relevant data will be extracted independently by two reviewers, analysed thematically and the findings reported qualitatively.

Discussion

The evidence produced by this review will help identify implementation and policy gaps to inform future implementation research/interventions studies using a variety of evidence-based strategies towards the prevention and control of NCDs due to unhealthy diets in the WHO Africa Region. Platforms such as peer review journals, policy briefs and conferences will be used to disseminate this review’s findings.
Sepsis: emerging pathogens and antimicrobial resistance in Ethiopian referral hospitals
Authors: Legese Melese Hailu , Asrat Daniel , Swedberg Göte , Hasan Badrul , Mekasha Amha , Getahun Tadesse , Worku Misganaw , Shimber Eminet Tesfaye , Getahun Seid , Ayalew Tsedale , Gizachew Birhan , Aseffa Abraham , Mihret Adane
Published: June 2022

Background

Sepsis due to multidrug resistant (MDR) bacteria is a growing public health problem mainly in low-income countries.

Methods

A multicenter study was conducted between October 2019 and September 2020 at four hospitals located in central (Tikur Anbessa and Yekatit 12), southern (Hawassa) and northern (Dessie) parts of Ethiopia. A total of 1416 patients clinically investigated for sepsis were enrolled. The number of patients from Tikur Anbessa, Yekatit 12, Dessie and Hawassa hospital was 501, 298, 301 and 316, respectively. At each study site, blood culture was performed from all patients and positive cultures were characterized by their colony characteristics, gram stain and conventional biochemical tests. Each bacterial species was confirmed using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI TOF). Antimicrobial resistance pattern of bacteria was determined by disc diffusion. Logistic regression analysis was used to assess associations of dependent and independent variables. A p-value < 0.05 was considered as statistically significant. The data was analyzed using SPSS version 25.

Results

Among 1416 blood cultures performed, 40.6% yielded growth. Among these, 27.2%, 0.3% and 13.1%, were positive for pathogenic bacteria, yeast cells and possible contaminants respectively. Klebsiella pneumoniae (26.1%), Klebsiella variicola (18.1%) and E. coli (12.4%) were the most frequent. Most K. variicola were detected at Dessie (61%) and Hawassa (36.4%). Almost all Pantoea dispersa (95.2%) were isolated at Dessie. Rare isolates (0.5% or 0.2% each) included Leclercia adecarboxylata, Raoultella ornithinolytica, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, Burkholderia cepacia, Kosakonia cowanii and Lelliottia amnigena. Enterobacteriaceae most often showed resistance to ampicillin (96.2%), ceftriaxone (78.3%), cefotaxime (78%), cefuroxime (78%) and ceftazidime (76.4%). MDR frequency of Enterobacteriaceae at Hawassa, Tikur Anbessa, Yekatit 12 and Dessie hospital was 95.1%, 93.2%, 87.3% and 67.7%, respectively. Carbapenem resistance was detected in 17.1% of K. pneumoniae (n = 111), 27.7% of E. cloacae (n = 22) and 58.8% of Acinetobacter baumannii (n = 34).

Conclusion

Diverse and emerging gram-negative bacterial etiologies of sepsis were identified. High multidrug resistance frequency was detected. Both on sepsis etiology types and MDR frequencies, substantial variation between hospitals was determined. Strategies to control MDR should be adapted to specific hospitals. Standard bacteriological services capable of monitoring emerging drug-resistant sepsis etiologies are essential for effective antimicrobial stewardship.
Consideration of specific key points improves outcome of decompression treatment in patients with endocrine orbitopathy: pre-/post-OP comparison and biomechanical simulation
Authors: Krause Matthias , Neuhaus Michael-Tobias , Sterker Ina , Bartella Alexander K. , Schönfeld Annika , Lethaus Bernd , Zimmerer Rüdiger , Gladilin Evgeny
Published: June 2022

Endocrine orbitopathy is typically treated by resecting orbital walls. This procedure reduces intraorbital pressure by releasing intraorbital tissue, effectively alleviating the symptoms. However, selection of an appropriate surgical plan for treatment of endocrine orbitopathy requires careful consideration because predicting the effects of one-, two-, or three-wall resections on the release of orbital tissues is difficult. Here, based on our experience, we describe two specific orbital sites (’key points’) that may significantly improve decompression results. Methodological framework of this work is mainly based on comparative analysis pre- and post-surgery tomographic images as well as image- and physics-based simulation of soft tissue outcome using the finite element modelling of mechanical soft tissue behaviour. Thereby, the optimal set of unknown modelling parameters was obtained iteratively from the minimum difference between model predictions and post-surgery ground truth data. This report presents a pre-/post-surgery study indicating a crucial role of these particular key points in improving the post-surgery outcome of decompression treatment of endocrine orbitopathy which was also supported by 3D biomechanical simulation of alternative two-wall resection plans. In particular, our experimental results show a nearly linear relationship between the resection area and amount of tissue released in the extraorbital space. However, a disproportionately higher volume of orbital outflow could be achieved under consideration of the two special key points. Our study demonstrates the importance of considering natural biomechanical obstacles to improved outcomes in two-wall resection treatment of endocrine orbitopathy. Further investigations of alternative surgery scenarios and post-surgery data are required to generalize the insights of this feasibility study.
Exploring the potential of taurolidine in inducing mobilization and detachment of colon cancer cells: a preliminary in-vitro study
Authors: Mikolajczyk Agata , Khosrawipour Veria , Lau Hien , Li Shiri , Migdal Pawel , Labbé Maya Karine , Kielan Wojciech , Nicpon Jakub , Stieglitz Sven , Khosrawipour Tanja
Published: June 2022

Background

Recently, taurolidine has been intensively studied on a variety of in-vitro cancer cell-lines and first data exhibit encouraging antitumoral effects. While the clinical use of taurolidine is considered, some studies with in-vivo experiments contradict this beneficial effect and even indicate advanced cancer growth. The aim of this study is to further investigate this paradox in-vivo effect by taurolidine and closely analyze the interaction of cancer cells with the surrounding environment following taurolidine exposure.

Methods

HT-29 (ATCC® HTB-38™) cells were treated with taurolidine at different concentrations and oxaliplatin using an in-vitro model. Morphological changes with respect to increasing taurolidine dosage were visualized and monitored using electron microscopy. Cytotoxicity of the agents as well as extent of cellular detachment by mechanical stress was measured for each substance using a colorimetric MTS assay.

Results

Both taurolidine and oxaliplatin exhibit cell toxicity on colon cancer cells. Taurolidine reshapes colon cancer cells from round into spheric cells and further induces cluster formation. When exposed to mechanical stress, taurolidine significantly enhances detachment of adherent colon carcinoma cells compared to the control (p < 0.05) and the oxaliplatin group (p < 0.05). This effect is dose dependent.

Conclusions

Beside its cytotoxic effects, taurolidine could also change mechanical interactions of cancer cells with their environment. Local cancer cell conglomerates could be mechanically mobilized and may cause metastatic growth further downstream. The significance of changes in cellular morphology caused by taurolidine as well as its interaction with the microenvironment must be further addressed in clinical cancer therapies. Further clinical studies are needed to evaluate both the safety and efficacy of taurolidine for the treatment of peritoneal surface malignancies.
Quantitative logging data clustering with hidden Markov model to assist log unit classification
Authors: Yabe Suguru , Hamada Yohei , Fukuchi Rina , Nomura Shunichi , Shigematsu Norio , Kiguchi Tsutomu , Ueki Kenta
Published: June 2022

Revealing subsurface structures is a fundamental task in geophysical and geological studies. Logging data are usually acquired through drilling projects, which constrain the subsurface structure, and together with the description of drill core samples, are used to distinguish geological units. Clustering is useful for interpreting logging data and making log unit classification and is usually performed by manual inspection of the data. However, the validity of clustering results with such subjective criteria may be questionable. This study proposed the application of a statistical clustering method, the hidden Markov model, to conduct unsupervised clustering of logging data. As logging data are aligned along the drilled hole, they and the geological structure hidden behind such sequential datasets can be regarded as observables and hidden states in the hidden Markov model. When log unit classification is manually conducted, depth dependency of logging data is usually focused. Therefore, we included depth information as observables to explicitly represent depth dependency of logging data. The model was applied to the following geological settings: the accretionary prism at the Nankai Trough, the onshore fault zone at the Kii Peninsula (southwest Japan), and the forearc basin at the Japan Trench. The optimum number of clusters were searched using a quantitative index. The clustering results using the hidden Markov model were consistent with previously reported classifications or lithological descriptions; however, our method allowed a more detailed division of logging data, which is useful to interpret geological structures, such as a fault or a fault zone. Therefore, the use of the hidden Markov model enabled us to clarify assumptions quantitatively and conduct clustering consistently for the entire depth range, even for different geological sites. The proposed method is expected to have wider applicability and extensibility for other types of data, including geochemical and structural geological data.

Graphical Abstract
Rapamycin golden jubilee and still the miraculous drug: a potent immunosuppressant, antitumor, rejuvenative agent, and potential contributor in COVID-19 treatment
Authors: Mohamed Mohamed A. , Elkhateeb Waill A. , Daba Ghoson M.
Published: June 2022

Although celebrating its golden jubilee, rapamycin’s importance keeps increasing by the day. Starting as a promising antifungal agent, then as a potent immunosuppressant, strong anticancer drug, and now rapamycin is attracting serious attention as a rejuvenative agent and a possible contributor in treating this era pandemic, COVID-19. Due to its diverse biological activities and promising medical applications, we aimed in this review to put rapamycin under the spot and highlight its discovery, famous microbial producers, reported biological activities, chemical structure, famous analogues, and biosynthesis. Moreover, discuss some rapamycin production approaches including solid-state fermentation, and stressing out producing strain. On the other hand, describe its action mechanism and trials to use it in treatment of COVID-19. Additionally, we highlighted some of the side effects accompanying its use, and describe some approaches reported to minimize these undesired effects. Finally, we report the current status of rapamycin and its analogues in global market, and discuss future prospects of this potent drug.
First record of the genus Acletoxenus (Diptera: Drosophilidae) and its predaceous species A. formosus (Leow, 1864) in Egypt, with some field observations and biological remarks
Authors: Nada Maha Salah Eldin , Ebrahim Ayman Mohey Eldin , El-Hawagry Magdi Shaaban Ali
Published: June 2022

Background

The genus Acletoxenus (tribe Gitonini, subfamily Steganinae, family Drosophilidae) is a small widespread genus, comprising only four species worldwide, namely: Acletoxenus indicus Malloch, 1929, A. quadristriatus Duda, 1936, A. meijerei Duda, 1924 in addition to A. formosus (Leow, 1864), the species of the present study. The larvae of Acletoxenus spp. are known as predators of whiteflies.

Results

The genus Acletoxenus and its predaceous species A. formosus (Leow, 1864) are recorded in the present study for the first time from Egypt. This species was found associated with the immature stages of the glasshouse whitefly, Trialeurodes vaporariorum Westwood, 1856 (Hemiptera: Aleyrodidae) feeding on the castor bean plant, Ricinus communis L. which has been grown at the Plant Protection Institute, Agricultural Research Center, Giza, Egypt. The morphological diagnoses, in situ predatory behavior in the field and ex situ biological remarks in the laboratory were discussed.

Conclusion

The predaceous drosophilid fly, Acletoxenus formosus (Leow, 1864), is recorded herein with its genus for the first time from Egypt as the second representative of the tribe Gitonini (subfamilies Steganinae, family Drosophilidae) in the country. The recording of this species in Egypt is of a great interest as it will encourage and lead to further research on different biological aspects. This drosophilid is a beneficial fly as its larvae are predators of immature stages of whiteflies (family Aleyrodidae) and it could be used as a potential biological control agent.
Establishment of a novel experimental model of infected anal fistula in rat
Authors: Zhao Meng , Wang Aitong , Zhang Leisheng , Yu Hao
Published: June 2022

Refractory Crohn's-like enterocutaneous fistula indicates the aggressive manifestation and lead to poor prognosis of patients. The development of multidisciplinary strategies for fistula administration largely subjects to the deficiency of animal model for disease remodeling and the underlying pathogenic mechanism. For the purpose, infected anal fistula model was conducted by BLV single-core electrolytic aluminum combined with dextran sodium sulfate. Notably, the inflammatory granulation tissue and inflammatory cell infiltration in the perianal tissue were arised on day 7 of the model by utilizing the Hematoxylin–eosin staining. With the aid of magnetic resonance imaging and signals of high-brightness. We intuitively observed the thickening and edema appeared in the fistula wall, which collectively suggested the formation of a fistula in the perianal area of the rat. Distinguish from the current models of anal fistula modeling including the body surface of fistula, backside of fistula and drainage wire of fistula, our model revealed multifaceted advantages such as quicker generation, higher modeling rate, preferable stability, better consistency, cost-effective, and in particular, more convenient to mimic clinical manifestations of anal fistula.
Real-time observation of neutrophil extracellular trap formation in the inflamed mouse brain via two-photon intravital imaging
Authors: Byun Da Jeong , Kim Young Min , Hyun Young-Min
Published: June 2022

Intravital imaging via two-photon microscopy (TPM) is a useful tool for observing and delineating biological events at the cellular and molecular levels in live animals in a time-lapse manner. This imaging method provides spatiotemporal information with minimal phototoxicity while penetrating a considerable depth of intact organs in live animals. Although various organs can be visualized using intravital imaging, in the field of neuroscience, the brain is the main organ whose cell-to-cell interactions are imaged using this technique. Intravital imaging of brain disease in mouse models acts as an abundant source of novel findings for studying cerebral etiology. Neutrophil infiltration is a well-known hallmark of inflammation; in particular, the crucial impact of neutrophils on the inflamed brain has frequently been reported in literature. Neutrophil extracellular traps (NETs) have drawn attention as an intriguing feature over the last couple of decades, opening a new era of research on their underlying mechanisms and biological effects. However, the actual role of NETs in the body is still controversial and is in parallel with a poor understanding of NETs in vivo. Although several experimental methods have been used to determine NET generation in vitro, some research groups have applied intravital imaging to detect NET formation in the inflamed organs of live mice. In this review, we summarize the advantages of intravital imaging via TPM that can also be used to characterize NET formation, especially in inflamed brains triggered by systemic inflammation. To study the function and migratory pattern of neutrophils, which is critical in triggering the innate immune response in the brain, intravital imaging via TPM can provide new perspectives to understand inflammation and the resolution process.
Modelling of cutting force and surface roughness of ultrasonic-assisted drilling using artificial neural network
Authors: Abdelkawy Abdallah
Published: June 2022

This paper presents artificial neural network modelling for the thrust force in terms of maximum and mean values and the surface roughness for drilling soda glass using ultrasonic-assisted drilling. The experimental parameters are the tool concentrations (normal and high), cutting speed, and feed rate. The feedforward architecture neural network is composed of 10 hidden layers with sigmoid function and output layer with linear function. Three models are developed for each response individually and then one model for the three outputs. The models between the neural network output and the target (experimental results) for training, validation, and test data are developed, and their coefficients of regression are reasonable for this experimental data. The suitable number of hidden layers is examined with mean square error, and it is found that it decreases with increasing the number of hidden layer. The three models are developed based on one output, and the model of the three outputs is very close and good representative for the experimental results. It is concluded that the variables can be controlled and optimized by the same conditions.
Pediatric anesthesia and achalasia: 10 years’ experience in peroral endoscopy myotomy management
Authors: Sbaraglia Fabio , Familiari Pietro , Maiellare Federica , Mecarello Marco , Scarano Annamaria , Del Prete Demetrio , Lamacchia Rosa , Antonicelli Federica , Rossi Marco
Published: June 2022

Background

Endoscopic treatment for achalasia (POEM) is a recently introduced technique that incorporates the concepts of natural orifice transluminal surgery. Although pediatric achalasia is rare, POEM has been episodically used in children since 2012. Despite this procedure entails many implications for airway management and mechanical ventilation, evidences about anesthesiologic management are very poor. We conducted this retrospective study to pay attention on the clinical challenge for pediatric anesthesiologists. We put special emphasis on the risk in intubation maneuvers and in ventilation settings.

Results

We retrieved data on children 18 years old and younger who underwent POEM in a single tertiary referral endoscopic center between 2012 and 2021. Demographics, clinical history, fasting status, anesthesia induction, airway management, anesthesia maintenance, timing of anesthesia and procedure, PONV, and pain treatment and adverse events were retrieved from the original database.

Thirty-one patients (3–18 years) undergoing POEM for achalasia were analyzed. In 30 of the 31 patients, rapid sequence induction was performed. All patients manifested consequences of endoscopic CO2 insufflation and most of them required a new ventilator approach. No life-threatening adverse events have been detected.

Conclusions

POEM procedure seems to be characterized by a low-risk profile, but specials precaution must be taken. The inhalation risk is actually due to the high rate of full esophagus patients, even if the Rapid Sequence Induction was effective in preventing ab ingestis pneumonia. Mechanical ventilation may be difficult during the tunnelization step. Future prospective trials will be necessary to individuate the better choices in such a special setting.
Impact of COVID-19 in Cervical and Breast Cancer Screening and Systemic Treatment in São Paulo, Brazil: An Interrupted Time Series Analysis
Authors: Duarte Mateus B.O. , Argenton Juliana L.P. , Carvalheira José B.C.
Published: June 2022

PURPOSE

COVID-19 caused a disruption in cancer management around the world, resulting in an estimated excess burden secondary to screening disruption and excess lag time for treatment initiation.

METHODS

We gathered information from primary reimbursement data sets of the public health system of São Paulo, Brazil, from April 2020 to November 2021, and compared these data with those of the pre–COVID-19 period. We used an interrupted time series model to estimate the effect of the COVID-19 pandemic on the rate of key procedures of breast and cervical cancer health care chain.

RESULTS

We estimated that 1,149,727, 2,693, and 713,616 pap smears, conizations, and mammograms, respectively, were missed or delayed during the COVID-19 pandemic, compared with those in the years immediately before the COVID-19 stay-at-home restrictions. Specifically, we observed an acute decrease of procedures after the COVID-19 stay-at-home restrictions, with a trend to recovery in the long term. Regarding the systemic treatment analysis, we observed a 25% reduction in the rate of initiation of adjuvant systemic treatment for early breast cancer (stage I/II). However, we did not find a clear effect on the other settings of systemic treatment for breast cancer. We estimated an excess of 156 patients starting palliative care for cervical cancer after the COVID-19 stay-at-home restrictions.

CONCLUSION

The COVID-19 pandemic significantly reduced the performance rate of pap smears, conizations, and mammograms. The initiation of adjuvant treatment for early-stage breast cancer was most susceptible to COVID-19's health system disruption. Furthermore, the downward trend of treatment of advanced cervical cancer was interrupted. Therefore, public health policies are urgently needed to decrease the incidence of advanced cervical and breast cancers caused by delayed diagnosis and treatment initiation. The COVID-19 control policies resulted in reduction of cancer patients' delivery of care. This study evaluated the pandemic's influence in key procedures of breast and cervical cancer chain of care in São Paulo, Brazil. We observed a substantial reduction in the number of mammograms, pap smears, and conizations performed since the onset of the COVID-19 pandemic. In addition, stage I and II breast cancer adjuvant treatment presented a reduced realization rate, whereas palliative treatment delivered for advanced cervical cancer increased. Our results support the need for public health policies focused on mitigating the long-term effects of COVID-19 in cancer-related mortality.
Management of Hyperglycemia in Hospitalized Adult Patients in Non-Critical Care Settings: An Endocrine Society Clinical Practice Guideline
Authors: Korytkowski Mary T , Muniyappa Ranganath , Antinori-Lent Kellie , Donihi Amy C , Drincic Andjela T , Hirsch Irl B , Luger Anton , McDonnell Marie E , Murad M Hassan , Nielsen Craig , Pegg Claire , Rushakoff Robert J , Santesso Nancy , Umpierrez Guillermo E
Published: June 2022

Background

Adult patients with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. These patients are at increased risk for adverse clinical outcomes in the absence of defined approaches to glycemic management.

Objective

To review and update the 2012 Management of Hyperglycemia in Hospitalized Patients in Non-Critical Care Settings: An Endocrine Society Clinical Practice Guideline and to address emerging areas specific to the target population of noncritically ill hospitalized patients with diabetes or newly recognized or stress-induced hyperglycemia.

Methods

A multidisciplinary panel of clinician experts, together with a patient representative and experts in systematic reviews and guideline development, identified and prioritized 10 clinical questions related to inpatient management of patients with diabetes and/or hyperglycemia. The systematic reviews queried electronic databases for studies relevant to the selected questions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make recommendations.

Results

The panel agreed on 10 frequently encountered areas specific to glycemic management in the hospital for which 15 recommendations were made. The guideline includes conditional recommendations for hospital use of emerging diabetes technologies including continuous glucose monitoring and insulin pump therapy; insulin regimens for prandial insulin dosing, glucocorticoid, and enteral nutrition–associated hyperglycemia; and use of noninsulin therapies. Recommendations were also made for issues relating to preoperative glycemic measures, appropriate use of correctional insulin, and diabetes self-management education in the hospital. A conditional recommendation was made against preoperative use of caloric beverages in patients with diabetes.

Conclusion

The recommendations are based on the consideration of important outcomes, practicality, feasibility, and patient values and preferences. These recommendations can be used to inform system improvement and clinical practice for this frequently encountered inpatient population.
Enhancing the Trustworthiness of the Endocrine Society’s Clinical Practice Guidelines
Authors: McCartney Christopher R , Corrigan Maureen D , Drake Matthew T , El-Hajj Fuleihan Ghada , Korytkowski Mary T , Lash Robert W , Lieb David C , McCall Anthony L , Muniyappa Ranganath , Piggott Thomas , Santesso Nancy , Schünemann Holger J , Wiercioch Wojtek , McDonnell Marie E , Murad M Hassan
Published: June 2022

In an effort to enhance the trustworthiness of its clinical practice guidelines, the Endocrine Society has recently adopted new policies and more rigorous methodologies for its guideline program. In this Clinical Practice Guideline Communication, we describe these recent enhancements—many of which reflect greater adherence to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to guideline development—in addition to the rationale for such changes. Improvements to the Society’s guideline development practices include, but are not limited to, enhanced inclusion of nonendocrinologist experts, including patient representatives, on guideline development panels; implementation of a more rigorous conflict/duality of interest policy; a requirement that all formal recommendations must be demonstrably underpinned by systematic evidence review; the explicit use of GRADE Evidence-to-Decision frameworks; greater use and explanation of standardized guideline language; and a more intentional approach to guideline updating. Lastly, we describe some of the experiential differences our guideline readers are most likely to notice.
Yttrium-90 Selective Internal Radiation Therapy Plus Cryoablation for Recurrent Adrenocortical Carcinoma With Liver Metastases
Authors: Lin Tung-Yen , Lin Kuan-Yu , Kuo Hung-Yang , Huang Kuo-How , Wang Chih-Yuan , Lin Yu-Lin , Shih Shyang-Rong , Liang Po-Chin
Published: June 2022

Advanced adrenocortical carcinoma (ACC) has a poor prognosis and is often resistant to the conventional regimens of mitotane administration and systemic chemotherapy. In addition to surgery, local therapeutic measures can be valuable. Here, we present the case of a 33-year-old woman who developed left retroperitoneal local recurrent ACC with hepatic and pulmonary metastases 1 year after radical adrenalectomy. The tumors progressed under chemotherapy and mitotane treatments. She was treated with yttrium-90 selective internal radiation therapy (90Y SIRT) for hepatic metastases and cryoablation of the local recurrent tumor, after which significant tumor shrinkage was observed. She then received radiofrequency ablation for the residual hepatic metastases and radiotherapy to the residual local recurrent tumor. Complete remission was achieved and maintained at least until the data cutoff day (15.8 months after the last treatment). This is the first published report of cryoablation in a patient with ACC and the third report of 90Y SIRT use for hepatic metastasis of ACC. Cryoablation and 90Y SIRT are local treatment choices for ACC that are worthy of further study.
Introduction
Authors: Facer Keri , Newfield Christopher
Published: June 2022

The authors organized a conference, “Global Higher Education in 2050: Imagining Universities for Sustainable Societies,” at the University of California, Santa Barbara, March 4–6, 2020, right before the campus was closed for eighteen months in response to the COVID-19 pandemic. The event's premise was that the futures of higher education will be plural, must be responsive to large international divergences, and must be actively created by global majorities rather than policy elites. This introduction describes the papers' common project of identifying the key elements in the higher education status quo and features that might lead toward unexpected futures. We summarize the three horizons methodology that guided some of the work. We also outline the activities of the third day, the workshop that sought a means of linking the present to the future. This work continues beyond the horizons of the papers published here.
Assessment of heavy metals in food and drug packaging materials
Authors: Mukhi Senna , Rukmini M S , Ajay Manjrekar Poornima , Iyyaswami Reghupathi , Sindhu H
Published: June 2022

Background: Food and drug packaging materials are an integral part of our everyday life.  Noxious elements can inadvertently be included in packaging materials in various stages of their production. Adulterants, adhesives, colorants and heavy metal interference are the common sources of contamination in food packaging materials. Heavy metal toxicity has far-reaching ill effects on living organisms. The present study aimed at qualitatively and quantitatively analysing heavy metal contamination of various materials that are used for food and drug packaging in India.

Methods: The qualitative detection was done by rapid assay and heavy metals were quantified with the help of inductively coupled plasma-optical emission spectrometry (ICP-OES). A total of 13 types of food and drug packaging materials were procured from local market and analysed for four heavy metals viz. arsenic (As), vanadium (V), mercury (Hg) and cadmium (Cd). The concentration of each heavy metal in the samples was compared with permitted values published by the European Council.

Results: Of the 13 samples, heavy metals were qualitatively detected in 10 samples. ICP­-OES values for quantitative estimation showed presence of heavy metal above permissible range in 10 of the studied samples for vanadium, all samples for arsenic, two samples for mercury and one sample for cadmium. Arsenic was found to be the commonest heavy metal contaminant, present in 13 samples above permissible limit.

Conclusions: The significantly higher concentration of heavy metal poses a potential health risk to the consumer and affects the quality of the food.
eXNVerify: coverage analysis for long and short-read sequencing data in clinical context
Authors: Porębski Sebastian , Stokowy Tomasz
Published: June 2022

Accurate identification of genetic variants to a large extent is based on the type of experimental technology, quality of the material and coverage of sequencing data obtained. The latter, coverage quality, highly influences variant calling accuracy and final diagnosis. Our motivation was to create a tool that will evaluate genome coverage and accelerate the introduction of long-read sequencing to medical diagnostics and clinical practice. The implementation was guided by the ease of use of the tool by users who are not proficient in using complex software. A Docker container is perfect for this purpose. Using Docker’s advantages (flexibility, mobility and ease of use of the proposed tools), we created eXNVerify. This is a tool for inspection of clinical data in the context of pathogenic variants search. The tool calculates clinical depth coverage (CDC) – a measure of coverage which we introduce to evaluate loci with pathogenic germline and somatic variants reported in ClinVar. The tool additionally provides visualization options for user-defined genes of interest. Finally, we present examples of BRCA1, TP53, CFTR application and results of a test conducted in the Extensive Sequence Dataset of Gold-Standard Samples for Benchmarking and Development. eXNVerify improves the diagnostic process of patients related to important genetic diseases and facilitates the assessment of genetic samples by diagnosticians. The use of Docker allows to run an analysis package and does not require any special technical preparation. Detailed examples are included in the GitHub project documentation  and the package can be downloaded directly from DockerHub using the command: docker pull porebskis/exnverify:1.0.
Consumers’ behavior in conversational commerce marketing based on messenger chatbots
Authors: Mehta Reena , Verghese Jose , Mahajan Shriya , Barykin Sergey , Bozhuk Svetlana , Kozlova Nelli , Vasilievna Kapustina Irina , Mikhaylov Alexey , Naumova Elena , Dedyukhina Natalia
Published: June 2022

Background: The increasing penetration of smartphones and the Internet in developing countries caused the rise of e-retail. Conversational commerce is highly increasing via interaction through messengers. To extract the benefits of both trends, companies have adopted messenger chatbots. These chatbots use Artificial intelligence and natural language processing to give live responses to the customer and assist online shopping on the messenger interface. This research aims to discover the factors that affect the use of messenger chatbots and their influence on attitude and behavior intention.

Methods: The research methodology includes the Technology Acceptance Model (TAM) with the variables of perceived usefulness, perceived ease of use, consumer trust, and anthropomorphism. The authors used an online survey for collecting the responses from 192 respondents and analyzed structural equation modelling.

Results: Customer trust has shown the most decisive influence on customer attitude followed by Perceived Usefulness, Perceived Ease of Use. Also, the use of chatbots to make online shopping faster significantly affects the use of messenger chatbots for online shopping in the future. The authors explore various factors resulting in consumers’ favor of accepting chatbots as an interface for m-commerce.

Conclusions: The findings indicate that organizations should design strategies to improve interaction with the customer by developing messenger chatbots for more trusting conversations. Further research could include a theoretical digital marketing approach to conversational commerce based on anthropomorphic digital technologies.
"Acute Kidney Injury predictive models: advanced yet far from application in resource-constrained settings."
Authors: Mrara Busisiwe , Paruk Fathima , Oladimeji Olanrewaju
Published: June 2022

Acute kidney injury (AKI) remains a major cause of morbidity and mortality in hospitalized patients, particularly critically ill patients. It poses a public health challenge in resource-constrained settings due to high administrative costs. AKI is commonly misdiagnosed due to its painless onset and late disruption of serum creatinine, which is the gold standard biomarker for AKI diagnosis. There is increasing research into the use of early biomarkers and the development of predictive models for early AKI diagnosis using clinical, laboratory, and imaging data. This field note provides insight into the challenges of using available AKI prediction models in resource-constrained environments, as well as perspectives that practitioners in these settings may find useful
Impact of pathogenic mutations of the GLUT1 glucose transporter on solute carrier dynamics using ComDYN enhanced sampling
Authors: Mouhib Halima , Higuchi Akiko , Abeln Sanne , Yura Kei , Feenstra K. Anton
Published: June 2022

Background: The solute carrier (SLC) family of membrane proteins is a large class of transporters for many small molecules that are vital for cellular function. Several pathogenic mutations are reported in the glucose transporter subfamily SLC2, causing Glut1-deficiency syndrome (GLUT1DS1, GLUT1DS2), epilepsy (EIG2) and cryohydrocytosis with neurological defects (Dystonia-9). Understanding the link between these mutations and transporter dynamics is crucial to elucidate their role in the dysfunction of the underlying transport mechanism, which we investigate using molecular dynamics simulations.

Methods: We studied pathogenic and non-pathogenic mutations, using a newly developed coarse-grained simulation approach ‘ComDYN’, which captures the ‘COMmon constraints DYNamics’ between both states of the solute carrier protein. To guarantee the sampling of large conformational changes, we only include common constraints of the elastic network introduced upon coarse-graining, which showed similar reference distances between both conformational states (≤1 Å difference).

Results: ComDYN is computationally efficient and sufficiently sensitive to capture effects of different mutations. Our results clearly indicate that the pathogenic mutation in GLUT1, G91D, situated at the highly conserved RXGRR motif between helices 2 and 3, has a strong impact on transporter function, as it blocks the protein from sampling both conformational states. In comparison, predictions from SIFT and PolyPhen only provided an impression of the impact upon mutation in the highly conserved RXGRR motifs, but yielded no clear differentiation between pathogenic and non-pathogenic mutations. 

Conclusions: Using our approach, we can explain the pathogenicity of the mutation G91D and some of the effects of other known pathogenic mutations, when we observe the configurations of the transmembrane helices, suggesting that their relative position is crucial for the correct functioning of the GLUT1 protein. To fully understand the impact of other mutations in the future, it is necessary to consider the effect of ligands, e.g., glucose, within the transport mechanism.