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Nevin Manimala Statistics

Do young patients with rectal cancer have outcomes comparable to those of their older counterparts? A statistical problem and countermeasure

Br J Surg. 2021 Mar 12;108(2):e83. doi: 10.1093/bjs/znaa015.

NO ABSTRACT

PMID:33711110 | DOI:10.1093/bjs/znaa015

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Nevin Manimala Statistics

Chronic pain after open inguinal hernia repair: expertise-based randomized clinical trial of heavyweight or lightweight mesh

Br J Surg. 2021 Mar 12;108(2):138-144. doi: 10.1093/bjs/znaa049.

ABSTRACT

BACKGROUND: There is a shortage of high-quality studies regarding choice of mesh in open anterior inguinal hernia repair in relation to long-term chronic pain. The authors hypothesized that heavyweight compared with lightweight mesh causes increased postoperative pain.

METHODS: An RCT was undertaken between 2007 and 2009 at two sites in Sweden. Men aged 25 years or older with an inguinal hernia evaluated in the outpatient clinic were randomized in an unblinded fashion to heavyweight or lightweight mesh for open anterior inguinal hernia repair. Data on pain affecting daily activities, as measured by the Short-Form Inguinal Pain Questionnaire 9-12 years after surgery, were collected as the primary outcome. Differences between groups were evaluated by generalized odds and numbers needed to treat.

RESULTS: A total of 412 patients were randomized; 363 were analysed with 320 questionnaires sent out. A total of 271 questionnaires (84.7 per cent) were returned; of these, 121 and 150 patients were in the heavyweight and lightweight mesh groups respectively. Pain affecting daily activities was more pronounced in patients randomized to heavyweight versus lightweight mesh (generalized odds 1.33, 95 per cent c.i. 1.10 to 1.61). This translated into a number needed to treat of 7.06 (95 per cent c.i. 4.28 to 21.44). Two reoperations for recurrence were noted in the heavyweight mesh group, and one in the lightweight mesh group.

CONCLUSION: A large-pore lightweight mesh causes significantly less pain affecting daily activities a decade after open anterior inguinal hernia repair. Registration number: NCT00451893 (http://www.clinicaltrials.gov).

PMID:33711123 | DOI:10.1093/bjs/znaa049

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Impact of COVID-19 on colorectal cancer presentation

Br J Surg. 2021 Mar 12;108(2):e81-e82. doi: 10.1093/bjs/znaa124.

NO ABSTRACT

PMID:33711133 | DOI:10.1093/bjs/znaa124

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Nevin Manimala Statistics

Extra base hits: Widespread empirical support for instantaneous multiple-nucleotide changes

PLoS One. 2021 Mar 12;16(3):e0248337. doi: 10.1371/journal.pone.0248337. eCollection 2021.

ABSTRACT

Despite many attempts to introduce evolutionary models that permit substitutions to instantly alter more than one nucleotide in a codon, the prevailing wisdom remains that such changes are rare and generally negligible or are reflective of non-biological artifacts, such as alignment errors. Codon models continue to posit that only single nucleotide change have non-zero rates. Here, we develop and test a simple hierarchy of codon-substitution models with non-zero evolutionary rates for only one-nucleotide (1H), one- and two-nucleotide (2H), or any (3H) codon substitutions. Using over 42, 000 empirical alignments, we find widespread statistical support for multiple hits: 61% of alignments prefer models with 2H allowed, and 23%-with 3H allowed. Analyses of simulated data suggest that these results are not likely to be due to simple artifacts such as model misspecification or alignment errors. Further modeling reveals that synonymous codon island jumping among codons encoding serine, especially along short branches, contributes significantly to this 3H signal. While serine codons were prominently involved in multiple-hit substitutions, there were other common exchanges contributing to better model fit. It appears that a small subset of sites in most alignments have unusual evolutionary dynamics not well explained by existing model formalisms, and that commonly estimated quantities, such as dN/dS ratios may be biased by model misspecification. Our findings highlight the need for continued evaluation of assumptions underlying workhorse evolutionary models and subsequent evolutionary inference techniques. We provide a software implementation for evolutionary biologists to assess the potential impact of extra base hits in their data in the HyPhy package and in the Datamonkey.org server.

PMID:33711070 | DOI:10.1371/journal.pone.0248337

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Nevin Manimala Statistics

A Machine Learning Explanation of the Pathogen-Immune Relationship of SARS-CoV-2 (COVID-19), and a Model to Predict Immunity and Therapeutic Opportunity: A Comparative Effectiveness Research Study

JMIRx Med. 2020 Oct 19;1(1):e23582. doi: 10.2196/23582. eCollection 2020 Jan-Dec.

ABSTRACT

BACKGROUND: Approximately 80% of those infected with COVID-19 are immune. They are asymptomatic unknown carriers who can still infect those with whom they come into contact. Understanding what makes them immune could inform public health policies as to who needs to be protected and why, and possibly lead to a novel treatment for those who cannot, or will not, be vaccinated once a vaccine is available.

OBJECTIVE: The primary objectives of this study were to learn if machine learning could identify patterns in the pathogen-host immune relationship that differentiate or predict COVID-19 symptom immunity and, if so, which ones and at what levels. The secondary objective was to learn if machine learning could take such differentiators to build a model that could predict COVID-19 immunity with clinical accuracy. The tertiary purpose was to learn about the relevance of other immune factors.

METHODS: This was a comparative effectiveness research study on 53 common immunological factors using machine learning on clinical data from 74 similarly grouped Chinese COVID-19-positive patients, 37 of whom were symptomatic and 37 asymptomatic. The setting was a single-center primary care hospital in the Wanzhou District of China. Immunological factors were measured in patients who were diagnosed as SARS-CoV-2 positive by reverse transcriptase-polymerase chain reaction (RT-PCR) in the 14 days before observations were recorded. The median age of the 37 asymptomatic patients was 41 years (range 8-75 years); 22 were female, 15 were male. For comparison, 37 RT-PCR test-positive patients were selected and matched to the asymptomatic group by age, comorbidities, and sex. Machine learning models were trained and compared to understand the pathogen-immune relationship and predict who was immune to COVID-19 and why, using the statistical programming language R.

RESULTS: When stem cell growth factor-beta (SCGF-β) was included in the machine learning analysis, a decision tree and extreme gradient boosting algorithms classified and predicted COVID-19 symptom immunity with 100% accuracy. When SCGF-β was excluded, a random-forest algorithm classified and predicted asymptomatic and symptomatic cases of COVID-19 with 94.8% AUROC (area under the receiver operating characteristic) curve accuracy (95% CI 90.17%-100%). In total, 34 common immune factors have statistically significant associations with COVID-19 symptoms (all c<.05), and 19 immune factors appear to have no statistically significant association.

CONCLUSIONS: The primary outcome was that asymptomatic patients with COVID-19 could be identified by three distinct immunological factors and levels: SCGF-β (>127,637), interleukin-16 (IL-16) (>45), and macrophage colony-stimulating factor (M-CSF) (>57). The secondary study outcome was the suggestion that stem-cell therapy with SCGF-β may be a novel treatment for COVID-19. Individuals with an SCGF-β level >127,637, or an IL-16 level >45 and an M-CSF level >57, appear to be predictively immune to COVID-19 100% and 94.8% (AUROC) of the time, respectively. Testing levels of these three immunological factors may be a valuable tool at the point of care for managing and preventing outbreaks. Further, stem-cell therapy via SCGF-β and M-CSF appear to be promising novel therapeutics for patients with COVID-19.

PMID:33711083 | PMC:PMC7924715 | DOI:10.2196/23582

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Electronic and thermodynamic properties of native point defects in V2O5: a first-principles study

Phys Chem Chem Phys. 2021 Mar 12. doi: 10.1039/d0cp06002j. Online ahead of print.

ABSTRACT

The formation of native point defects in semiconductors and their behaviors play a crucial role in material properties. Although the native defects of V2O5 include vacancies, self-interstitials, and antisites, only oxygen vacancies have been extensively explored. In this work, we carried out first-principles calculations to systematically study the properties of possible native defects in V2O5. The electronic structure and the formation energy of each defect were calculated using the DFT+U method. Defect concentrations were estimated using a statistical model with a constraint of charge neutrality. We found that the vanadyl vacancy is a shallow acceptor that could supply holes to the system. However, the intrinsic p-type doping in V2O5 hardly occurred because the vanadyl vacancy could be readily compensated by the more stable donor, i.e., the oxygen vacancy and oxygen interstitial, instead of holes. The oxygen vacancy is the most dominant defect under oxygen-deficient conditions. However, under extreme O-rich conditions, a deep donor of oxygen interstitial becomes the major defect species. The dominant oxygen vacancy under synthesized conditions plays an important role in determining the electronic conductivity of V2O5. It induces the formation of compensating electron polarons. The polarons are trapped at V centers close to the vacancy site with the effective escaping barriers of around 0.6 eV. Such barriers are higher than that of the isolated polaron hopping (0.2 eV). The estimated polaron mobilities obtained from kinetic Monte Carlo simulations confirmed that oxygen vacancies act as polaron-trapping sites, which diminishes the polaron mobility by 4 orders of magnitude. Nevertheless, when the sample is synthesized at elevated temperatures, a number of thermally activated polarons in samples are quite high due to the high concentrations of oxygen vacancies. These polarons can contribute as charge carriers of intrinsic n-type semiconducting V2O5.

PMID:33711089 | DOI:10.1039/d0cp06002j

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Interleukin-8 is increased in chronic kidney disease in children, but not related to cardiovascular disease

J Bras Nefrol. 2021 Mar 12:S0101-28002021005027301. doi: 10.1590/2175-8239-JBN-2020-0225. Online ahead of print.

ABSTRACT

INTRODUCTION: In this study, we aimed to detect the cytokine that is involved in the early stage of chronic kidney disease and associated with cardiovascular disease.

METHODS: We included 50 patients who were diagnosed with predialytic chronic kidney disease and 30 healthy pediatric patients in Ege University Medical Faculty Pediatric Clinic, İzmir/Turkey. Interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-13 (IL-13), and transforming grow factor-β1 (TGF-β1) levels (pg/mL) were measured by ELISA. Carotid-femoral pulse wave velocity (PWV), augmentation index (Aix), carotid intima media thickness (cIMT), and left ventricular mass index (LVMI) were evaluated as markers of cardiovascular disease. The presence of a cardiovascular disease marker was defined as an abnormality in any of the parameters (cIMT, PWV, Aix, and left ventricular mass index (SVKI)). The patient group was divided into two groups as with and without cardiovascular disease.

RESULTS: Mean Aix and PWV values were higher in CKD patients than controls (Aix: CKD 32.8±11.11%, healthy subjects: 6.74±6.58%, PWV CKD: 7.31±4.34m/s, healthy subjects: 3.42±3.01m/s, respectively; p=0.02, p=0.03). The serum IL-8 levels of CKD were significantly higher than of healthy subjects 568.48±487.35pg/mL, 33.67±47.47pg/mL, respectively (p<0.001). There was no statistically significant difference between IL-8, IL-10, IL-13, TGF-1, in CKD patients with and without cardiovascular disease (p> 0.05).

DISCUSSION: IL-8 is the sole cytokine that increases in pediatric patients with chronic kidney disease among other cytokines (IL-10, IL-13 and TGF-β1). However, we did not show that IL-8 is related to the presence of cardiovascular disease.

PMID:33711092 | DOI:10.1590/2175-8239-JBN-2020-0225

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Nevin Manimala Statistics

Understanding variations and influencing factors on length of stay for T2DM patients based on a multilevel model

PLoS One. 2021 Mar 12;16(3):e0248157. doi: 10.1371/journal.pone.0248157. eCollection 2021.

ABSTRACT

AIM: Shortening the length of stay (LOS) is a potential and sustainable way to relieve the pressure that type 2 diabetes mellitus (T2DM) patients placed on the public health system.

METHOD: Multi-stage random sampling was used to obtain qualified hospitals and electronic medical records for patients discharged with T2DM in 2018. A box-cox transformation was adopted to normalize LOS. Multilevel model was used to verify hospital cluster effect on LOS variations and screen potential factors for LOS variations from both individual and hospital levels.

RESULT: 50 hospitals and a total of 12,888 T2DM patients were included. Significant differences in LOS variations between hospitals, and a hospital cluster effect on LOS variations (t = 92.188, P<0.001) was detected. The results showed that female patients, patients with new rural cooperative’ medical insurance, hospitals with more beds, and hospitals with faster bed turnovers had shorter LOS. Conversely, elderly patients, patients with urban workers’ medical insurance, patients requiring surgery, patients with the International Classification of Diseases coded complication types E11.1, E11.2, E11.4, E11.5, and other complications cardiovascular diseases, grade III hospitals, hospitals with a lower doctor-to-nurse ratio, and hospitals with more daily visits per doctor had longer LOS.

CONCLUSIONS: The evidence proved that hospital cluster effect on LOS variation did exist. Complications and patients features at individual level, as well as organization and resource characteristics at hospital level, had impacted LOS variations to varying degrees. To shorten LOS and better meet the medical demand for T2DM patients, limited health resources must be allocated and utilized rationally at hospital level, and the patients with the characteristics of longer LOS risk must be identified in time. More influencing factors on LOS variations at different levels are still worth of comprehensive exploration in the future.

PMID:33711043 | DOI:10.1371/journal.pone.0248157

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Nevin Manimala Statistics

The prevalence of Helicobacter pylori infection in inflammatory bowel disease in China: A case-control study

PLoS One. 2021 Mar 12;16(3):e0248427. doi: 10.1371/journal.pone.0248427. eCollection 2021.

ABSTRACT

BACKGROUND & AIMS: Helicobacter pylori (H. pylori) infection remains high in China though the incidence of inflammatory bowel disease (IBD) has increased. Our aim was to investigate the relationship between the prevalence of H. pylori and inflammatory bowel disease.

METHODS: Hospitalized IBD patients including Crohn’s disease (CD) and ulcerative colitis (UC) who had tested H. pylori antibody were enrolled. Controls were chose from age- and sex- matched healthy physical examination people who had H. pylori antibody test in a 1:2 fashion (IBD patients:controls). IBD medical history was recorded. All patients were typed by the Montreal classification. Mayo Clinic score and the Harvey-Bradshaw Severity Index were used to evaluate their disease activity. Patients and controls that had H. pylori eradication therapy before were excluded.

RESULTS: Two hundred and sixty IBD patients including 213 CD patients and 47 UC patients, and 520 controls were involved in this study. The prevalence of H. pylori infection in IBD patients (9.6%, 25/260) and IBD newly diagnosed patients (12.1%, 8/66), as well as CD patients (8.9%, 19/213) including CD newly diagnosed patients (10.6%, 5/47) and UC patients (12.8%, 6/47) was significantly lower than controls (29.8%, 155/520) (p = 2.796*10-10, 0.007, 5.723*10-9, 0.016, 0.014), while there was no statistically difference between UC newly diagnosed patients and the controls, and IBD patients with different disease type, disease activity and treatment history.

CONCLUSIONS: H. pylori infection had a negative association with IBD, especially CD.

PMID:33711050 | DOI:10.1371/journal.pone.0248427

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Nevin Manimala Statistics

Towards sustainable transport policy framework: A rail-based transit system in Klang Valley, Malaysia

PLoS One. 2021 Mar 12;16(3):e0248519. doi: 10.1371/journal.pone.0248519. eCollection 2021.

ABSTRACT

This study examines the sustainable transport policy framework in the case of railway development in Klang Valley, Malaysia. It is guided by the main principle that sustainable transport policy is a result of the integration of broad policy instruments that range from infrastructure provision and management, technological improvements, regulation, information, awareness, education, and pricing and taxation. Although this study is mainly qualitative, performance data available at the ASEAN Statistics Division, World Bank Open Data and Global Competitiveness Reports. This is followed by in-person interviews with experts who have vast knowledge, experience, and direct participation in sustainable railway development in Malaysia, especially those related to the Klang Valley development. The main findings have indicated that the current framework in Malaysia meets the criteria of sustainable development policy framework, which are essentially constituted within environmental protection. It also constitutes the pursuance of long-term growth in terms of economic and societal needs. Nonetheless, the rail-based transit system in Malaysia is highly driven by the Government and there is no clear sign indicating that the public is shifting from the road and private transport to rail-based services.

PMID:33711053 | DOI:10.1371/journal.pone.0248519