bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of frictional braking noise based on brake dynamometer test and artificial intelligent algorithms
Authors: Wang Shuwen , Zhong Liangwei , Niu Yayun , Liu Shuangxia , Wang Shaofan , Li Ke , Wang Lijing , Barton David
Published: December 2021

Based on brake noise dynamometer test data, combined with the artificial intelligent algorithms, frictional braking noise is quantitatively analyzed and predicted in this study. To achieve this goal, a frictional braking noise prediction method is indicatively proposed, which consists of two main parts: first, based on the experimental data obtained from the brake noise dynamometer tests, and combining with the improved Long-Short-Term Memory (LSTM) algorithm, the coefficients of friction (COFs) are predicted under various braking test conditions. Then, based on the predicted braking COFs and other selected critical braking parameters, the quantitative prediction of frictional braking noise is obtained by means of the optimized eXtreme Gradient Boosting (XGBoost) algorithm. Finally, the inherent features of the XGBoost algorithm are employed to qualitatively analyze the importance of the main factors affecting the frictional braking noise. The prediction algorithms of COFs and frictional braking noise are validated by the brake dynamomter test data, and the R2 (R square) scores of both the LSTM and XGBoost prediction algorithms are 0.9, which verifies the feasibility of both algorithms. The main contribution of this work is to predict the braking noise based on a large set of test data and combined with the LSTM and XGBoost artificial intelligent algorithms, which can significantly save time for the brake system development and braking performance testing, and has significance to the rapid prediction of braking frictional noise and fast NVH (noise, vibration, and harshness) optimal design of frictional braking systems.
The Perception of Ramped Pulse Shapes in Cochlear Implant Users
Authors: Navntoft Charlotte Amalie , Landsberger David M. , Barkat Tania Rinaldi , Marozeau Jeremy
Published: December 2021

The electric stimulation provided by current cochlear implants (CI) is not power efficient. One underlying problem is the poor efficiency by which information from electric pulses is transformed into auditory nerve responses. A novel stimulation paradigm using ramped pulse shapes has recently been proposed to remedy this inefficiency. The primary motivation is a better biophysical fit to spiral ganglion neurons with ramped pulses compared to the rectangular pulses used in most contemporary CIs. Here, we tested the hypotheses that ramped pulses provide more efficient stimulation compared to rectangular pulses and that a rising ramp is more efficient than a declining ramp. Rectangular, rising ramped and declining ramped pulse shapes were compared in terms of charge efficiency and discriminability, and threshold variability in seven CI listeners. The tasks included single-channel threshold detection, loudness-balancing, discrimination of pulse shapes, and threshold measurement across the electrode array. Results showed that reduced charge, but increased peak current amplitudes, was required at threshold and most comfortable levels with ramped pulses relative to rectangular pulses. Furthermore, only one subject could reliably discriminate between equally-loud ramped and rectangular pulses, suggesting variations in neural activation patterns between pulse shapes in that participant. No significant difference was found between rising and declining ramped pulses across all tests. In summary, the present findings show some benefits of charge efficiency with ramped pulses relative to rectangular pulses, that the direction of a ramped slope is of less importance, and that most participants could not perceive a difference between pulse shapes.
Molecular and cellular mechanisms that regulate human erythropoiesis
Authors: Caulier Alexis L. , Sankaran Vijay G.
Published: December 2021

To enable effective oxygen transport, ∼200 billion red blood cells (RBCs) need to be produced every day in the bone marrow through the fine-tuned process of erythropoiesis. Erythropoiesis is regulated at multiple levels to ensure that defective RBC maturation or overproduction can be avoided. Here, we provide an overview of different layers of this control, ranging from cytokine signaling mechanisms that enable extrinsic regulation of RBC production to intrinsic transcriptional pathways necessary for effective erythropoiesis. Recent studies have also elucidated the importance of posttranscriptional regulation and highlighted additional gatekeeping mechanisms necessary for effective erythropoiesis. We additionally discuss the insights gained by studying human genetic variation affecting erythropoiesis and highlight the discovery of BCL11A as a regulator of hemoglobin switching through genetic studies. Finally, we provide an outlook of how our ability to measure multiple facets of this process at single-cell resolution, while accounting for the impact of human variation, will continue to refine our knowledge of erythropoiesis and how this process is perturbed in disease. As we learn more about this intricate and important process, additional opportunities to modulate erythropoiesis for therapeutic purposes will undoubtedly emerge.
Overcoming IMiD resistance in T-cell lymphomas through potent degradation of ZFP91 and IKZF1
Authors: Wu Wenchao , Nelson Geoffrey M. , Koch Raphael , Donovan Katherine A. , Nowak Radosław P. , Heavican-Foral Tayla B. , Nirmal Ajit J. , Liu Huiyun , Yang Lei , Duffy Jessica , Powers Foster , Stevenson Kristen E. , Jones Marcus Kenneth , Ng Samuel Y. , Wu Gongwei , Jain Salvia , Xu Ran , Amaka Sam , Trevisani Christopher , Donaldson Nicholas L. , Hagner Patrick R. , de Leval Laurence , Gaulard Philippe , Iqbal Javeed , Thakurta Anjan , Fischer Eric S. , Adelman Karen , Weinstock David M.
Published: December 2021

Immunomodulatory (IMiD) agents like lenalidomide and pomalidomide induce the recruitment of IKZF1 and other targets to the CRL4CRBN E3 ubiquitin ligase, resulting in their ubiquitination and degradation. These agents are highly active in B-cell lymphomas and a subset of myeloid diseases but have compromised effects in T-cell lymphomas (TCLs). Here, we show that 2 factors determine resistance to IMiDs among TCLs. First, limited CRBN expression reduces IMiD activity in TCLs but can be overcome by newer-generation degrader CC-92480. Using mass spectrometry, we show that CC-92480 selectively degrades IKZF1 and ZFP91 in TCL cells with greater potency than pomalidomide. As a result, CC-92480 is highly active against multiple TCL subtypes and showed greater efficacy than pomalidomide across 4 in vivo TCL models. Second, we demonstrate that ZFP91 functions as a bona fide transcription factor that coregulates cell survival with IKZF1 in IMiD-resistant TCLs. By activating keynote genes from WNT, NF-kB, and MAP kinase signaling, ZFP91 directly promotes resistance to IKZF1 loss. Moreover, lenalidomide-sensitive TCLs can acquire stable resistance via ZFP91 rewiring, which involves casein kinase 2–mediated c-Jun inactivation. Overall, these findings identify a critical transcription factor network within TCLs and provide clinical proof of concept for the novel therapy using next-generation degraders.
COVID-19 vaccination in patients with immune thrombocytopenia
Authors: Visser Chantal , Swinkels Maurice , van Werkhoven Erik D. , Croles F. Nanne , Noordzij-Nooteboom Heike S. , Eefting Matthijs , Last-Koopmans Suzanne M. , Idink Cecile , Westerweel Peter E. , Santbergen Bart , Jobse Pieter A. , Baboe Fazil ,   RECOVAC-IR Consortium, te Boekhorst Peter A. W. , Leebeek Frank W. G. , Levin Mark-David , Kruip Marieke J. H. A. , Jansen A. J. Gerard
Published: December 2021

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder that is characterized by low platelet count and increased bleeding risk. COVID-19 vaccination has been described as a risk factor for de novo ITP, but the effects of COVID-19 vaccination in patients with ITP are unknown. We aimed to investigate the effects of COVID-19 vaccination in patients with ITP on platelet count, bleeding complications, and ITP exacerbation (≥50% decline in platelet count, or nadir platelet count < 30 × 109/L with a >20% decrease from baseline, or use of rescue therapy). Platelet counts in patients with ITP and healthy controls were collected immediately before and 1 and 4 weeks after the first and second vaccinations. Linear mixed-effects modeling was applied to analyze platelet counts over time. We included 218 patients with ITP (50.9% female; mean age, 55 years; and median platelet count, 106 × 109/L) and 200 healthy controls (60.0% female; mean age, 58 years; median platelet count, 256 × 109/L). Platelet counts decreased by 6.3% after vaccination. We did not observe any difference in decrease between the groups. Thirty patients with ITP (13.8%; 95% confidence interval [CI], 9.5-19.1) had an exacerbation and 5 (2.2%; 95% CI, 0.7-5.3) suffered from a bleeding event. Risk factors for ITP exacerbation were platelet count < 50 × 109/L (odds ratio [OR], 5.3; 95% CI, 2.1-13.7), ITP treatment at time of vaccination (OR, 3.4; 95% CI, 1.5-8.0), and age (OR, 0.96 per year; 95% CI, 0.94-0.99). Our study highlights the safety of COVID-19 vaccination in patients with ITP and the importance of the close monitoring of platelet counts in a subgroup of patients with ITP. Patients with ITP with exacerbation responded well on therapy.
Emergency medicine in Brazil: historical perspective, current status, and future challenges
Authors: Oliveira J. e Silva Lucas , Herpich Henrique , Puls Henrique Alencastro , Myers Justin Guy , Schubert Daniel Ujakow Correa , Freitas Ana Paula , Santos Jule , Melo de Andrade Marcus Vinicius , Penna Guimarães Hélio
Published: December 2021

Background

Emergency medicine (EM) in Brazil has achieved critical steps toward its development in the last decades including its official recognition as a specialty in 2016. In this article, we worked in collaboration with the Brazilian Association of Emergency Medicine (ABRAMEDE) to describe three main aspects of EM in Brazil: (1) brief historical perspective; (2) current status; and (3) future challenges.

Main text

In Brazil, the first EM residency program was created in 1996. Only 20 years later, the specialty was officially recognized by national regulatory bodies. Prior to recognition, there were only 2 residency programs. Since then, 52 new programs were initiated. Brazil has now 54 residency programs in 16 of the 27 federative units. As of December 2020, 192 physicians have been board certified as emergency physicians in Brazil. The shortage of formal EM-trained physicians is still significant and at this point it is not feasible to have all Brazilian emergency care units and EDs staffed only with formally trained emergency physicians. Three future challenges were identified including the recognition of EM specialists in the house of Medicine, the need of creating a reliable training curriculum despite highly heterogeneous emergency care practice across the country, and the importance of fostering the development of academic EM as a way to build a strong research agenda and therefore increase the knowledge about the epidemiology and organization of emergency care.

Conclusion

Although EM in Brazil has accomplished key steps toward its development, there are several obstacles before it becomes a solid medical specialty. Its continuous development will depend on special attention to key challenges involving recognition, reliability, and research.
In-depth assembly of organ and development dissected Picrorhiza kurroa proteome map using mass spectrometry
Authors: Kumari Manglesh , Pradhan Upendra Kumar , Joshi Robin , Punia Ashwani , Shankar Ravi , Kumar Rajiv
Published: December 2021

Background

Picrorhiza kurroa Royle ex Benth. being a rich source of phytochemicals, is a promising high altitude medicinal herb of Himalaya. The medicinal potential is attributed to picrosides i.e. iridoid glycosides, which synthesized in organ-specific manner through highly complex pathways. Here, we present a large-scale proteome reference map of P. kurroa, consisting of four morphologically differentiated organs and two developmental stages.

Results

We were able to identify 5186 protein accessions (FDR < 1%) providing a deep coverage of protein abundance array, spanning around six orders of magnitude. Most of the identified proteins are associated with metabolic processes, response to abiotic stimuli and cellular processes. Organ specific sub-proteomes highlights organ specialized functions that would offer insights to explore tissue profile for specific protein classes. With reference to P. kurroa development, vegetative phase is enriched with growth related processes, however generative phase harvests more energy in secondary metabolic pathways. Furthermore, stress-responsive proteins, RNA binding proteins (RBPs) and post-translational modifications (PTMs), particularly phosphorylation and ADP-ribosylation play an important role in P. kurroa adaptation to alpine environment. The proteins involved in the synthesis of secondary metabolites are well represented in P. kurroa proteome. The phytochemical analysis revealed that marker compounds were highly accumulated in rhizome and overall, during the late stage of development.

Conclusions

This report represents first extensive proteomic description of organ and developmental dissected P. kurroa, providing a platform for future studies related to stress tolerance and medical applications.
Comparison between 5-aminolevulinic acid photodynamic diagnosis and narrow-band imaging for bladder cancer detection
Authors: Hagimoto Hiroki , Makita Noriyuki , Mine Yuta , Kokubun Hidetoshi , Murata Shiori , Abe Yohei , Kubota Masashi , Tsutsumi Naofumi , Yamasaki Toshinari , Kawakita Mutsushi
Published: December 2021

Background

To compare 5-aminolevulinic acid (5-ALA)-mediated photodynamic diagnosis (PDD) with narrow-band imaging (NBI) for cancer detection during transurethral resection of bladder tumour (TURBT).

Methods

Between June 2018 and October 2020, 114 patients and 282 lesions were included in the analysis. Patients were orally administered 5-ALA (20 mg/kg) 2 h before TURBT. The bladder was inspected with white light (WL), PDD, and NBI for each patient, and all areas positive by at least one method were resected or biopsied. The imaging data were then compared to the pathology results.

Results

The sensitivities of WL, PDD, and NBI for detecting urothelial carcinoma were 88.1%, 89.6%, and 76.2%, respectively. The specificity, positive predictive value, and negative predictive value for detecting urothelial carcinoma were 47.5%, 80.9%, and 61.3%, respectively, for WL; 22.5%, 74.5%, and 46.2%, respectively, for PDD; and 46.3%, 78.2%, and 43.5%, respectively, for NBI. PDD was significantly more sensitive than NBI for all lesions (p < 0.001) and carcinoma in situ (CIS) lesions (94.6% vs. 54.1%, p < 0.001).

Conclusions

PDD can increase the detection rate of bladder cancer, compared to NBI, by greater than 10%. Therefore, 100% of CIS lesions can be detected by adding PDD to WL.
Tocilizumab improves 28-day survival in hospitalized patients with severe COVID-19: an open label, prospective study
Authors: Karampitsakos Theodoros , Malakounidou Elli , Papaioannou Ourania , Dimakopoulou Vasilina , Zarkadi Eirini , Katsaras Matthaios , Tsiri Panagiota , Tsirikos Georgios , Georgiopoulou Vasiliki , Oikonomou Ioanna , Davoulos Christos , Velissaris Dimitrios , Sampsonas Fotios , Marangos Markos , Akinosoglou Karolina , Tzouvelekis Argyris
Published: December 2021

Background

Data on the safety and efficacy profile of tocilizumab in patients with severe COVID-19 needs to be enriched.

Methods

In this open label, prospective study, we evaluated clinical outcomes in consecutive patients with COVID-19 and PaO2/FiO2 < 200 receiving tocilizumab plus usual care versus usual care alone. Tocilizumab was administered at the time point that PaO2/FiO2 < 200 was observed. The primary outcome was 28-day mortality. Secondary outcomes included time to discharge, change in PaO2/FiO2 at day 5 and change in WHO progression scale at day 10.

Findings

Overall, 114 patients were included in the analysis (tocilizumab plus usual care: 56, usual care: 58). Allocation to usual care was associated with significant increase in 28-day mortality compared to tocilizumab plus usual care [Cox proportional-hazards model: HR: 3.34, (95% CI: 1.21–9.30), (p = 0.02)]. There was not a statistically significant difference with regards to hospital discharge over the 28 day period for patients receiving tocilizumab compared to usual care [11.0 days (95% CI: 9.0 to 16.0) vs 14.0 days (95% CI: 10.0–24.0), HR: 1.32 (95% CI: 0.84–2.08), p = 0.21]. ΔPaO2/FiO2 at day 5 was significantly higher in the tocilizumab group compared to the usual care group [42.0 (95% CI: 23.0–84.7) vs 15.8 (95% CI: − 19.4–50.3), p = 0.03]. ΔWHO scale at day 10 was significantly lower in the tocilizumab group compared to the usual care group (-0.5 ± 2.1 vs 0.6 ± 2.6, p = 0.005).

Conclusion

Administration of tocilizumab, at the time point that PaO2/FiO2 < 200 was observed, improved survival and other clinical outcomes in hospitalized patients with severe COVID-19 irrespective of systemic inflammatory markers levels.
Engineering Rhodosporidium toruloides for limonene production
Authors: Liu Sasa , Zhang Mengyao , Ren Yuyao , Jin Guojie , Tao Yongsheng , Lyu Liting , Zhao Zongbao K. , Yang Xiaobing
Published: December 2021

Background

Limonene is a widely used monoterpene in the production of food, pharmaceuticals, biofuels, etc. The objective of this work was to engineer Rhodosporidium toruloides as a cell factory for the production of limonene.

Results

By overexpressing the limonene synthase (LS), neryl pyrophosphate synthase (NPPS)/geranyl pyrophosphate synthase and the native hydroxy-methyl-glutaryl-CoA reductase (HMGR), we established a baseline for limonene production based on the mevalonate route in Rhodosporidium toruloides. To further enhance the limonene titer, the acetoacetyl-CoA thiolase/HMGR (EfMvaE) and mevalonate synthase (EfMvaS) from Enterococcus faecalis, the mevalonate kinase from Methanosarcina mazei (MmMK) and the chimeric enzyme NPPS-LS were introduced in the carotenogenesis-deficient strain. The resulting strains produced a maximum limonene titer of 393.5 mg/L.

Conclusion

In this study, we successfully engineered the carotenogenesis yeast R. toruloides to produce limonene. This is the first report on engineering R. toruloides toward limonene production based on NPP and the fusion protein SltNPPS-CltLS. The results demonstrated that R. toruloides is viable for limonene production, which would provide insights into microbial production of valuable monoterpenes.
Dentoskeletal effects of early class III treatment protocol based on timing of intervention in children
Authors: Nucci Ludovica , Costanzo Caterina , Carfora Marco , d’Apuzzo Fabrizia , Franchi Lorenzo , Perillo Letizia
Published: December 2021

Background

To detect the optimal timing of intervention based on different cervical vertebral maturation stage (CS1-2 vs. CS3-4) for the treatment of Class III malocclusion with early Class III protocol.

Methods

A total sample of 43 patients (23 females, 20 males) ranging between 7 and 13 years of age with dentoskeletal Class III malocclusion treated with the modified SEC III (Splints, Elastic and Chincup) protocol divided into two groups based on the cervical vertebral maturation stages (CS1-2 and CS3-4) was included in this retrospective observational longitudinal study. Patient compliance was assessed using a 2-point Likert scale. Statistical comparisons between the two groups were performed with independent sample t tests.

Results

No statistically significant differences for any of the cephalometric variables describing the baseline dentoskeletal features were found between the two groups except for the mandibular unit length that was significantly greater in the pubertal group (P = 0.005). The modified SEC III protocol produced favorable sagittal outcomes in both groups, whereas no statistically significant T1-T2 changes were found between the CS1-2 and CS3-4 groups for any of the angular and linear measurements. No significant differences were found in the prevalence rates of the degree of collaboration between the two groups (P = 1.000).

Conclusions

No significant differences between prepubertal and pubertal patients were found in the sagittal and vertical dentoskeletal changes with the modified SEC III protocol. Thus, this early Class III treatment produced similar favorable effects in growing subjects regardless of the cervical vertebral maturation stages from CS1 to CS4.
Prevalence and risk factors of burnout among Lebanese community pharmacists in the era of COVID-19 pandemic: results from the first national cross-sectional survey
Authors: Youssef Dalal , Youssef Janet , Hassan Hamad , Abou-Abbas Linda
Published: December 2021

Background

Community pharmacists (CPs) are increasingly facing occupational challenges as a result of the COVID-19 pandemic, putting them at high risk of burnout. This study aimed to assess the prevalence of burnout among Lebanese CPs during the COVID-19 pandemic and to identify its associated factors.

Methods

An online survey was conducted among Lebanese CPs between February 1st and March 30, 2021. Collected data included information on sociodemographic characteristics, exposure and work-related variables, the Copenhagen burnout inventory (CBI), and the COVID-19 threat perception scale. Prevalence of burnout was calculated. Multiple logistic regressions were performed to identify the factors associated with the three burnout domains.

Results

A total of 387 CPs participated in the survey. Of the total, 53.7% were females; and 43.2% were aged less than 40 years old. The prevalence of moderate-to-high personal, work-related and client-related burnout was 77.8%, 76.8, and 89.7%, respectively. Younger age, staff pharmacist, working more than 40 h per week, high perceived COVID-19 threat were associated with a moderate-to-high likelihood of burnout in all three domains. However, altruistically accepting the risks of caring for COVID-19 patients was the only variable that was associated with a lower likelihood of burnout in all three domains.

Conclusion

An alarming prevalence of personal, work-related and client-related burnout was revealed among Lebanese CPs. This study has many implications for practice and provides a framework for establishing policy interventions to reduce burnout levels among Lebanese CPs. Preventive strategies and interventions on individual and organizational basis are recommended.
Exercise Training Intensity and the Fitness-Fatness Index in Adults with Metabolic Syndrome: A Randomized Trial
Authors: Ramos Joyce S. , Dalleck Lance C. , Fennell Mackenzie , Martini Alex , Welmans Talita , Stennett Rebecca , Keating Shelley E. , Fassett Robert G. , Coombes Jeff S.
Published: December 2021

Background

Cardiorespiratory fitness and fatness (notably central obesity) are mediating factors of the metabolic syndrome (MetS) and consequent cardiovascular disease (CVD)/mortality risk. The fitness-fatness index (FFI) combines these factors and has been reported to be a better indicator of CVD and all-cause mortality risk, beyond the capacity of either fitness or fatness alone.

Objective

This study sought to investigate the effects of different exercise intensities on FFI in adults with MetS.

Methods

This was a sub-study of the ‘Exercise in the prevention of Metabolic Syndrome’ (EX-MET) multicentre trial. Ninety-nine adults diagnosed with MetS according to the International Diabetes Federation criteria were randomized to one of the following 16-week exercise interventions: i) moderate-intensity continuous training (MICT) at 60–70% HRpeak for 30 min/session (n = 34, 150 min/week); ii) 4 × 4 min bouts of high-intensity interval training at 85–95% HRpeak, interspersed with 3-min active recovery at 50–70% HRpeak (n = 34, 38 min/session, 114 min/week); and iii) 1 × 4 min bout of HIIT at 85–95% HRpeak (n = 31, 17 min/session, 51 min/week). Cardiorespiratory fitness (peak oxygen uptake, V̇O2peak) was determined via indirect calorimetry during maximal exercise testing and fatness was the ratio of waist circumference-to-height (WtHR). FFI was calculated as V̇O2peak in metabolic equivalents (METs) divided by WtHR. A clinically meaningful response to the exercise intervention was taken as a 1 FFI unit increase.

Results

Seventy-seven participants completed pre and post testing to determine FFI. While there was no significant between group difference (p = 0.30), there was a small group x time interaction effect on FFI [F(2, 73) = 1.226; η2 = 0.01], with numerically greater improvements following HIIT (4HIIT, + 16%; 1HIIT, + 11%) relative to MICT (+ 7%). There was a greater proportion of participants who had a clinically meaningful change in FFI following high-volume HIIT (60%, 15/25) and low-volume HIIT (65%, 17/26) compared to MICT (38%, 10/26), but with no significant between-group difference (p = 0.12). A similar trend was found when a sub-analysis comparing the FFI between those with type 2 diabetes (MICT, 33%, 3/9; high-volume HIIT, 64%, 7/11; and low-volume HIIT, 58%, 7/12) and without type 2 diabetes (MICT, 41%, 7/17; high-volume HIIT, 57%, 8/14; low-volume HIIT, 71%, 10/14).

Conclusion

Although there were no statistically significant differences detected between groups, this study suggests that the response to changes in FFI in adults with MetS may be affected by exercise intensity, when numerical differences between exercise groups are considered. Further research is warranted.

Trial registration number and date of registration: ClinicalTrials.gov NCT01676870; 31/08/2012.
Modeling the Cost-Effectiveness of Adjuvant Chemotherapy for Stage III Colon Cancer in South African Public Hospitals
Authors: Pumpalova Yoanna , Rogers Alexandra M. , Tan Sarah Xinhui , Herbst Candice-lee , Ruff Paul , Neugut Alfred I. , Hur Chin
Published: December 2021

PURPOSE

Cancer incidence is rising in low- and middle-income countries, where resource constraints often complicate therapeutic decisions. Here, we perform a cost-effectiveness analysis to identify the optimal adjuvant chemotherapy strategy for patients with stage III colon cancer treated in South African (ZA) public hospitals.

METHODS

A decision-analytic Markov model was developed to compare lifetime costs and outcomes for patients with stage III colon cancer treated with six adjuvant chemotherapy regimens in ZA public hospitals: fluorouracil, leucovorin, and oxaliplatin for 3 and 6 months; capecitabine and oxaliplatin (CAPOX) for 3 and 6 months; capecitabine for 6 months; and fluorouracil/leucovorin for 6 months. Transition probabilities were derived from clinical trials to estimate risks of toxicity, disease recurrence, and survival. Societal costs and utilities were obtained from literature. The primary outcome was the incremental cost-effectiveness ratio in international dollars (I$) per disability-adjusted life-year (DALY) averted, compared with no therapy, at a willingness-to-pay (WTP) threshold of I$13,006.56.

RESULTS

CAPOX for 3 months was cost-effective (I$5,381.17 and 5.74 DALYs averted) compared with no adjuvant chemotherapy. Fluorouracil, leucovorin, and oxaliplatin for 6 months was on the efficiency frontier with 5.91 DALYs averted but, with an incremental cost-effectiveness ratio of I$99,021.36/DALY averted, exceeded the WTP threshold.

CONCLUSION

In ZA public hospitals, CAPOX for 3 months is the cost-effective adjuvant treatment for stage III colon cancer. The optimal strategy in other settings may change according to local WTP thresholds. Decision analytic tools can play a vital role in selecting cost-effective cancer therapeutics in resource-constrained settings.
Identification of Genetic Risk Factors for Familial Urinary Bladder Cancer: An Exome Sequencing Study
Authors: Pemov Alexander , Wegman-Ostrosky Talia , Kim Jung , Koutros Stella , Douthitt Brenna , Jones Kristine , Zhu Bin , Baris Dalsu , Schwenn Molly , Johnson Alison , Karagas Margaret R. , Carter Brian D. , McCullough Marjorie L. , Landi Maria Teresa , Freedman Neal D. , Albanes Demetrius , Silverman Debra T. , Rothman Nathaniel , Caporaso Neil E. , Greene Mark H. , Fraumeni Joseph F. , Stewart Douglas R.
Published: December 2021

PURPOSE

Previous studies have shown an approximately two-fold elevation in the relative risk of urinary bladder cancer (UBC) among people with a family history that could not be entirely explained by shared environmental exposures, thus suggesting a genetic component in its predisposition. Multiple genome-wide association studies and recent gene panel sequencing studies identified several genetic loci that are associated with UBC risk; however, the list of UBC-associated variants and genes is incomplete.

MATERIALS AND METHODS

We exome sequenced eight patients from three multiplex UBC pedigrees and a group of 77 unrelated familial UBC cases matched to 241 cancer-free controls. In addition, we examined pathogenic germline variation in 444 candidate genes in 392 The Cancer Genome Atlas UBC cases.

RESULTS

In the pedigrees, segregating variants were family-specific although the identified genes clustered in common pathways, most notably DNA repair ( MLH1 and MSH2) and cellular metabolism ( IDH1 and ME1). In the familial UBC group, the proportion of pathogenic and likely pathogenic variants was significantly higher in cases compared with controls ( P = .003). Pathogenic and likely pathogenic variant load was also significantly increased in genes involved in cilia biogenesis ( P = .001). In addition, a pathogenic variant in CHEK2 (NM_007194.4:c.1100del; p.T367Mfs*15) was over-represented in cases (variant frequency = 2.6%; 95% CI, 0.71 to 6.52) compared with controls (variant frequency = 0.21%; 95% CI, 0.01 to 1.15), but was not statistically significant.

CONCLUSION

These results point to a complex polygenic predisposition to UBC. Despite heterogeneity, the genes cluster in several biologically relevant pathways and processes, for example, DNA repair, cilia biogenesis, and cellular metabolism. Larger studies are required to determine the importance of CHEK2 in UBC etiology.
The Regulation of Phoenixin: A Fascinating Multidimensional Peptide
Authors: McIlwraith Emma K , Zhang Ningtong , Belsham Denise D
Published: December 2021

The phoenixin (PNX) peptide is linked to the control of reproduction, food intake, stress, and inflammation. However, little is known about what regulates its gene and protein expression, information that is critical to understand the physiological role of PNX. In this review, we summarize what is known about the transcriptional control of Pnx and its receptor Gpr173. A main function of PNX is as a positive regulator of the hypothalamic-pituitary-gonadal axis, but there is a lack of research on its control by reproductive hormones and peptides. PNX is also associated with food intake, and its expression is linked to feeding status, fatty acids, and glucose. It is influenced by environmental and hormonal-induced stress. The regulation of Pnx in most contexts remains an enigma, in part due to conflicting and negative results. An extensive analysis of the response of the Pnx gene to factors related to reproduction, metabolism, stress, and inflammation is required. Analysis of the Pnx promoter and epigenetic regulation must be considered to understand how this level of control contributes to its pleiotropic effects. PNX is now linked to a broad range of functions, but more research on its gene regulation is required to understand its place in overall physiology and therapeutic potential.
Physical Activity Levels in Six Native American Communities Using the FITT-VP Approach
Authors: Treuth Margarita S. , Poirier Lisa , Pardilla Marla , Redmond Leslie , Gittelsohn Joel
Published: December 2021

Purpose

This study aimed to describe physical activity (PA) via the frequency, intensity, time, type, volume, and progression (FITT-VP) principles of Native Americans (NA), it is necessary to understand their current PA. The purpose was to 1) evaluate PA levels utilizing FITT-VP principles and 2) compare the patterns of PA in NA men and women.

Methods

Recruitment and evaluation (n = 586) took place as part of the OPREVENT2 study baseline evaluation. The International Physical Activity Questionnaire–Short Form assessed frequency (days per week), intensity (walking, moderate, vigorous), and time (minutes per day). The total MET-minutes for the previous 7 d provided the volume of activity.

Results

The NA sample was 45.8 ± 15.1 yr of age, with a body mass index of 31.5 ± 6.4 kg·m−2. The FIT-V corresponded to 4.7 ± 2.3 d·wk−1, walking (3.3 METs intensity), 52 ± 47 min·d−1, and 2536 ± 2203 MET·min−1. The men (n = 162) reported a greater frequency of 3.2 ± 2.5 d·wk−1 (P = 0.007) of vigorous activity lasting 55 ± 50 min·d−1 compared with the women (n = 433) with 2.6 ± 2.5 d·wk−1 of vigorous activity lasting 34 ± 38 min·d−1. The men reported higher MET-minutes than did the women (P = 0.0001). Overall, 71% of men and 77% of women met the recommended PA guidelines.

Conclusions

Given that the majority of NA report adequate walking time and frequency, interventions are needed to improve moderate- and vigorous-intensity aerobic fitness, as well as muscular strength and endurance, neuromotor, and flexibility activities.
sgDI-tector: defective interfering viral genome bioinformatics for detection of coronavirus subgenomic RNAs
Authors: Di Gioacchino Andrea , Legendre Rachel , Rahou Yannis , Najburg Valérie , Charneau Pierre , Greenbaum Benjamin D. , Tangy Frédéric , van der Werf Sylvie , Cocco Simona , Komarova Anastassia V.
Published: December 2021

Coronavirus RNA-dependent RNA polymerases produce subgenomic RNAs (sgRNAs) that encode viral structural and accessory proteins. User-friendly bioinformatic tools to detect and quantify sgRNA production are urgently needed to study the growing number of next-generation sequencing (NGS) data of SARS-CoV-2. We introduced sgDI-tector to identify and quantify sgRNA in SARS-CoV-2 NGS data. sgDI-tector allowed detection of sgRNA without initial knowledge of the transcription-regulatory sequences. We produced NGS data and successfully detected the nested set of sgRNAs with the ranking M > ORF3a > N>ORF6 > ORF7a > ORF8 > S > E>ORF7b. We also compared the level of sgRNA production with other types of viral RNA products such as defective interfering viral genomes.
Evaluation of endoscopic variceal band ligation sessions in obliteration of esophageal varices
Authors: Alvi Haris , Zuberi Bader Faiyaz , Rasheed Tazeen , Ibrahim Muhammad Asad
Published: December 2021

Objective: To determine number of sessions of Endoscopic variceal band ligation required to obliterate the esophageal varices.

Methods: This study was conducted at Civil Hospital Karachi between June 2018 to April 2019. All patients undergoing endoscopic Variceal Band Ligation (EVBL) were inducted. Number of sessions of band ligation required to obliterate the varices were recorded. Number of EVBL sessions were correlated with Child-Pugh’s Score and etiology of CLD by χ2 test, while it was compared with duration of Chronic Liver Disease (CLD) by One-way ANOVA test.

Results: One hundred ninety-two patients fulfilling selection criteria were admitted after informed consent. These included 101 (52.6%) males and 91 (47.4%) females. Most common cause of cirrhosis was HCV (66.7%) in our patients. Most of the patients were in Child Class-B (71.9%). Majority of patients (52.6%) underwent 3 sessions of EVBL while 68 (35.4%) underwent 4 sessions of EVBL. Duration of CLD was analyzed with number of sessions of EVBL by One-Way ANOVA test and it showed significant more sessions of EVBL were done with longer duration of CLD (p <0.001).

Conclusion: Most patients underwent 3-4 sessions of EVBL for obliteration of varices. Number of EVBL sessions increased significantly with duration of disease.

doi: https://doi.org/10.12669/pjms.36.2.1144

How to cite this:Alvi H, Zuberi BF, Rasheed T, Ibrahim MA. Evaluation of endoscopic variceal band ligation sessions in obliteration of esophageal varices. Pak J Med Sci. 2020;36(2):37-41. doi: https://doi.org/10.12669/pjms.36.2.1144

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Effect of gastric residual volume monitoring on incidence of ventilator-associated pneumonia in mechanically ventilated patients admitted to intensive care unit
Authors: Faramarzi Elnaz , Mahmoodpoor Ata , Hamishehkar Hadi , Shadvar Kamran , Iranpour Afshin , Sabzevari Tara , Sanaie Sarvin
Published: December 2021

Objectives: The value of gastric residual volume (GRV) monitoring in ventilator-associated pneumonia (VAP) has frequently been questioned in the past years. In this trial, the effect of GRV on the frequency of VAP was evaluated in critically ill patients under mechanical ventilation.

Methods: This descriptive study was carried out on 150 adult patients admitted to the intensive care unit over a 14-month period, from October 2015 to January 2017. GRV was measured every three hours, and gastric intolerance was defined as GRV>250 cc. The incidence of vomiting and VAP, GRV, length of mechanical ventilation and ICU stay, APACHE II and SOFA scores, and mortality rate were noted.

Results: The mean APACHEII and SOFA scores, ICU length of stay, and duration of mechanical ventilation in the GRV>250ml group were significantly higher than in the GRV≤250 ml group (P<0.05). Also, a significantly higher number of patients in the GRV>250ml group experienced infection (62.3%) and vomiting (71.7%) compared with the GRV≤250 group (P<0.01). The highest OR was observed for SOFA score >15 and APACHE II >30, which increased the risk of GVR>250 ml by 10.09 (1.01-99.97) and 8.78 (1.49-51.58), respectively. Moreover, the increase in GVR was found to be higher in the non-survivor than in the survivor group.

Conclusion: Increased GRV did not result in increased rates of VAP, ICU length of stay, and mortality. Therefore, the routine measurement of GRV as an important element of the VAP prevention bundle is not recommended in critically ill patients.

doi: https://doi.org/10.12669/pjms.36.2.1321

How to cite this:

Faramarzi E, Mahmoodpoor A, Hamishehkar H, Shadvar K, Iranpour A, Sabzevari T, et al. Effect of gastric residual volume monitoring on incidence of ventilator-associated pneumonia in mechanically ventilated patients admitted to intensive care unit. Pak J Med Sci. 2020;36(2):48-53. doi: https://doi.org/10.12669/pjms.36.2.1321

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Nomos and canon in Byzantium: the case of the confiscation of the holy vessels during the reign of Alexios I Comnenus.
Authors: ΠΑΝΑΓΟΠΟΥΛΟΥ AΓΓΕΛΙΚΗ
Published: December 2021

Στο άρθρο διερευνώνται η σχέση νόμων και κανόνων στο Βυζάντιο, η στάση του βυζαντινού αυτοκράτορα απέναντι στους κανόνες και την εκκλησία γενικότερα, καθώς και τα όρια της νομοθετικής εξουσίας του, με αφορμή την έριδα που απασχόλησε το Βυζάντιο για περίπου δεκαπέντε χρόνια (1081-1095) ως αποτέλεσμα της εκποίησης από τον Αλέξιο Α’ Κομνηνό των ιερών σκευών, προκειμένου να χρηματοδοτηθούν μισθοφορικά στρατεύματα για την αντιμετώπιση του νορμανδικού κινδύνου μετά την κατάληψη του Δυρραχίου από τους Νορμανδούς τον Οκτώβριο του 1081. Η εξίσωση νόμων και κανόνων από την Νεαρά 131 του Ιουστιανού το 545, καθώς και η ασαφής θέση των νομικών του 12ου αιώνα απέναντι στη σχέση νόμων και κανόνων, ως αποτέλεσμα της στενής σχέσης Εκκλησίας και Πολιτείας στο Βυζάντιο, των δύο όψεων της μίας χριστιανικής αυτοκρατορίας, αντικατοπτρίζονται στη χρήση των όρων «νόμος» και «κανόνας» με μία διάθεση εξίσωσής τους στην Αλεξιάδα της Άννας Κομνηνής, που καταγράφει τα σχετικά με την έριδα
The construction of rare disease discourse on YouTube: highlighting a disparity between policy rhetoric and patient practices around public engagement
Authors: Hanchard Matthew
Published: December 2021

Background: Policy rhetoric around the 6,000-8,000 rare diseases affecting 300 million people worldwide often focuses on public engagement. Meanwhile, medical authorities tend either to treat patients with rare diseases as pre-categorised data sources, proffer to them notions of technological self-care as empowerment, or recruit them as advocacy allies. Conversely, people living with rare diseases often mobilise and engage with one another in self-organised communities via social media to share discussion, information, and resources. How rare disease discourse forms on specific social media platforms, the role of different actors (including medical authorities and algorithms), and its relation to public engagement policy are poorly understood.

Methods: This paper examines data on YouTube video watching/sharing (gathered from YouTube’s API via DMI’s ‘Data Tools for YouTube’) through social network analysis (read through a controversy analysis lens).

Results: The paper identifies eight patterns – each revolving around different levels of: focus on rare disease content; engagement between content and viewers, i.e. through likes, dislikes, and surrounding particular videos; permeability of videos between categories; and repetition in viewers watching the same video. Across six of the patterns, the paper finds a rare disease issue-network forming, where discourse is constructed through three distinct communication strategies, each garnering a different form of engagement.

Conclusions: Overall, the paper highlights a disconnect between how rare disease discourse is enacted on YouTube and policy promises of public engagement, with potential spaces for dialogue often closed off by medical authorities. To close, the paper provides recommendations for how policymakers might engage with and facilitate more inclusive forms of social media interaction between specific rare disease related communities and clinicians to develop more meaningful forms of knowledge exchange.
Clinical implication of adjuvant chemotherapy according to mismatch repair status in patients with intermediate-risk stage II colon cancer: a retrospective study
Authors: Kang Byung Woog , Baek Dong Won , Chang Eunhye , Kim Hye Jin , Park Su Yeon , Park Jun Seok , Choi Gyu Seog , Baek Jin Ho , Kim Jong Gwang
Published: December 2021

Background: The present study evaluated the clinical implications of adjuvant chemotherapy according to the mismatch repair (MMR) status and clinicopathologic features of patients with intermediate- and high-risk stage II colon cancer (CC).Methods: This study retrospectively reviewed 5,774 patients who were diagnosed with CC and underwent curative surgical resection at Kyungpook National University Chilgok Hospital. The patients were enrolled according to the following criteria: (1) pathologically diagnosed with primary CC; (2) stage II CC classified based on the 7th edition of the American Joint Committee on Cancer staging system; (3) intermediate- and high-risk features; and (4) available test results for MMR status. A total of 286 patients met these criteria and were included in the study. Results: Among the 286 patients, 54 (18.9%) were identified as microsatellite instability-high (MSI-H) or deficient MMR (dMMR). Although all the patients identified as MSI-H/dMMR showed better survival outcomes, T4 tumors and adjuvant chemotherapy were identified as independent prognostic factors for survival. For the intermediate-risk patients identified as MSI-low (MSI-L)/microsatellite stable (MSS) or proficient MMR (pMMR), adjuvant chemotherapy exhibited a significantly better disease-free survival (DFS) but had no impact on overall survival (OS). Oxaliplatin-containing regimens showed no association with DFS or OS. Adjuvant chemotherapy was not associated with DFS in intermediate-risk patients identified as MSI-H/dMMR. Conclusion: The current study found that the use of adjuvant chemotherapy was correlated with better DFS in MSI-L/MSS or pMMR intermediate-risk stage II CC patients.
Factors of Slowing Down the Economic Growth of Modern Russia
Authors: Basovskaya Elena , Basovskiy Leonid
Published: December 2021

The analysis of Rosstat data made it possible to establish that the inequality of wages in a region depends on the average value of wages in this region. Based on cross-sectional data across regions, a model has been built showing that wage inequality is largely determined by the level of wages in the region. Analysis of the relationship between the level of remuneration of various categories of personnel in the region in relation to the average level of remuneration by region on the basis of cross-analysis of these regions made it possible to establish the following. The level of remuneration of managers and specialists is associated with a positive correlation with the average level of remuneration in the region, the level of remuneration of workers and employees is associated with a negative correlation with the average level of remuneration in the region.

The higher the wages in the region, the more managers and specialists gain from this and the more workers and employees lose. The level of remuneration of workers in the regions is closely related to the negative correlation with the level of remuneration of managers and specialists. The growth in the level of remuneration in the region is reflected, first of all, in the growth in the level of remuneration for managers and specialists. This is due, firstly, to the fact that in post-industrial technological structures the role of specialists increases and the role of workers in the production of goods and services decreases, which is reflected in the assessment of their contribution to value creation. In addition, the segmentation of the labor market has an impact, its division into parts, between which effective social ties do not work. The upper segment, in which the more “profitable” jobs are distributed, has more executive and specialist jobs, while the lower segment includes the majority of office and blue-collar jobs.
Management Analysis of the Economic Security of Enterprises
Authors: Dvoretskaya Yu. , Kovaleva N. , Kuznetsova O.
Published: December 2021

The unstable conditions of the market economy force the leadership of economic entities to especially carefully monitor the provision of economic security. An important tool in the activities of the economic security services (ECS) of enterprises can be management analysis tools. The goal of the study is to identify the most effective elements of the management analysis method, through which economic security specialists can protect firms from internal threats as effectively as possible. In article the author systematized theoretical aspects of ensuring economic security of the enterprises, presented results of observation and the analysis of work of services of economic security in 40 firms of the real sector of economy of the Central Federal District (CFD) and also offered key indicators for assessment of the weakest points in activity of experts of ECS. The author recommended key indicators for evaluation: forecasting the activities of enterprises, their effectiveness in terms of alternative projects, investment security. The author believes that key indicators should be calculated and analyzed as part of the express monitoring of enterprises in order to identify potential economic threats as quickly as possible, but easily. In order to assess the forecasting of the financial and economic activities of enterprises and the effectiveness of their functioning in the context of alternative projects, specialists of economic security services should, first of all, subject the operating processes of the company to checks: supply, production, sales.