Nevin Manimala

J Biomed Inform. 2022 Feb 12:104008. doi: 10.1016/j.jbi.2022.104008. Online ahead of print.

ABSTRACT

Generalized Linear Mixed Model is one of the most pervasive class of statistical models. It is widely used in the medical domain. Training such models in a collaborative setting often entails privacy risks. Standard privacy preserving mechanisms such as differential privacy can be used to mitigate the privacy risk during training the model. However, experimental evidence suggests that adding differential privacy to the training of the model can cause significant utility loss which makes the model impractical for real world usage. Therefore, it becomes clear that the specific class of generalized linear mixed models which lose their usability under differential privacy requires a different approach for privacy preserving model training. In this work, we propose a value-blind training method in a collaborative setting for generalized linear mixed models. In our proposed training method, the central server optimizes model parameters for a generalized linear mixed model without ever getting access to the raw training data or intermediate computation values. Intermediate computation values that are shared by the collaborating parties with the central server are encrypted using homomorphic encryption. Experimentation on multiple datasets suggests that the model trained by our proposed method achieves very low error rate while preserving privacy. To the best of our knowledge, this is the first work that performs a systematic privacy analysis of generalized linear mixed model training in collaborative setting.

PMID:35167978 | DOI:10.1016/j.jbi.2022.104008

Int J Infect Dis. 2022 Feb 12:S1201-9712(22)00097-2. doi: 10.1016/j.ijid.2022.02.019. Online ahead of print.

ABSTRACT

BACKGROUND: Low ADAMTS 13 Activity has been suggested as an interplaying factor in the pathogenesis of COVID-19, considering that it is a thrombo-inflammatory disease with high risk of microthrombosis.

OBJECTIVES: The study aimed to explore the correlation between ADAMTS13 activity and the pathophysiological pathway of COVID-19.

PATIENTS/METHODS: We carried out a retrospective observational study of 87 COVID-19 patients in Nmc Royal Hospital, Abu Dhabi, UAE. ADAMTS13 activity was measured and compared with patients’ characteristics and clinical outcomes.

RESULTS: Low ADAMTS13 level was associated with pneumonia (p=0.007), severity of COVID-19 (p<0.001), and mechanical ventilation rates (p=0.018). Death was more frequently observed among patients (5 patients) with low ADAMTS13 activity compared to normal activity (1 patient), as well as inflammatory markers. Decreased ADAMTS13 levels increased the risk of pneumonia, severity of COVID-19, need for mechanical ventilation, and use of anticoagulants ((OR= 4.75, 95%CI: [1.54-18.02], p=0.011), (OR= 6.50, 95%CI: [2.57-17.74], p<0.001), (OR= 4.10, 95%CI: [1.29-15.82], p=0.024), (OR=8.00, 95%CI: (3.13-22.16), p<0.001), respectively). The low ADAMTS13 activity group had a slightly longer time to viral clearance than the normal ADAMTS13 group, but it was not statistically significant. (20 days, 95% CI: [16-27] days, vs. 17 days, 95% CI: [13-22] days, p=0.08, Log rank= 3.1).

CONCLUSION: Low ADAMTS13 activity has been linked to pneumonia, COVID-19 severity, use of anticoagulants, and need for mechanical ventilation, but not to mortality. We propose rADAMTS13 as a novel treatment for severe COVID-19.

PMID:35167969 | DOI:10.1016/j.ijid.2022.02.019

J Perinat Med. 2022 Feb 14. doi: 10.1515/jpm-2021-0575. Online ahead of print.

ABSTRACT

OBJECTIVES: To examine the relationship between postpartum depression (PPD), mode of delivery (MOD), and indication for unscheduled cesarean delivery (uCD).

METHODS: Patients with antenatal and postpartum Edinburgh Postnatal Depression Scale (EPDS) scores were compared by MOD and indication for uCD if applicable. Patients with an antenatal EPDS>12 were excluded to ascertain the incidence of new depression. The primary outcome was EPDS≥13 by MOD. The secondary outcome was EPDS≥13 by indication for uCD.

RESULTS: Seven hundred and thirty eight patients met inclusion criteria. There were statistically significant differences in MOD by age, race, BMI, and multi-gestation pregnancy. Patients delivered via uCD had a higher rate of peripartum complications and NICU admission. There were no differences in medical comorbidities or use of psychiatric medications by MOD. There was no difference in EPDS by MOD. The rate of PPD was higher in patients with uCD for non-reassuring fetal heart tones (NRFHT) compared to other indications for uCD (p=0.02).

CONCLUSIONS: While there was no difference in the incidence of PPD by MOD, the incidence of PPD was higher among patients delivered via uCD for NRFHT. These findings may have implications for patient counseling, post-operative mental health surveillance, and support of postpartum patients.

PMID:35166090 | DOI:10.1515/jpm-2021-0575

Int J Nurs Educ Scholarsh. 2022 Feb 15;19(1). doi: 10.1515/ijnes-2021-0127.

ABSTRACT

The objective of this study was to examine differences in principles from the cognitive load theory (CLT) combined with active learning strategies. To examine these differences, simple to complex activities were imbedded into two active learning instructional strategies: cooperative learning (CPL) and problem-based learning (PBL) and evaluated for its impact on mental effort for learning and intrinsic cognitive load. A two-within repeated-measures design was used in a nursing fundamentals classroom. The simple and complex activities were grounded in recommendations from the CLT and validated by nurse experts. The instructional strategies of CPL and PBL were chosen based on recommendations from the literature. Results revealed no statistically significant differences. A small interaction showed a decrease in mental effort and intrinsic load when problem-based learning was used. Progressing learning activities from simple to complex, informed by the CLT, offers an approach to designing instruction in nursing classrooms when using active learning strategies.

PMID:35166089 | DOI:10.1515/ijnes-2021-0127

J Korean Med Sci. 2022 Feb 14;37(6):e45. doi: 10.3346/jkms.2022.37.e45.

ABSTRACT

BACKGROUND: The objective of this study was to investigate the trend of self-injurious behavior (SIB) among persons who were directly impacted by coronavirus disease 2019 (COVID-19), especially those with pre-existing mental disorders.

METHODS: Using the National Health Insurance Service-COVID-19 database cohort, the monthly SIB rate was calculated by COVID-19 subgroups (i.e., positive for COVID-19 test, negative for COVID-19 test, and non-COVID-19 test [control]). In addition, moderated regression analysis was utilized to examine the statistical difference of SIB (suicide attempt and non-suicidal self-injury using ICD-10 code) trend between COVID-19 subgroups and with and without pre-existing mental disorder.

RESULTS: A total of 328,373 persons were included in the cohort study. Of these, 212,678 had been tested for COVID-19, and 7,713 of them were confirmed positive. During the pandemic peak, the “negative for COVID-19” group showed a large increase (P = 0.003) in SIB rates compared to the control group, the “positive for COVID-19” group showed a decreasing trend, but not significant (P = 0.314). Among those who were tested for COVID-19, those with pre-existing mental disorders showed an increasing trend of SIB compared to those without pre-existing mental disorders, however statistically insignificant (P = 0.137).

CONCLUSION: Our results suggest that people who are tested for COVID-19 are at a high risk of SIB during the peak COVID-19 pandemic. Therefore, screening for suicide risk and psychological interventions is needed for these high-risk groups.

PMID:35166081 | DOI:10.3346/jkms.2022.37.e45

Adv Clin Exp Med. 2022 Feb 15. doi: 10.17219/acem/145946. Online ahead of print.

ABSTRACT

BACKGROUND: Both intraoperative hypotension and hypertension have been reported to increase the occurrence of acute kidney injury (AKI). However, the impact of the intraoperative pulse pressure (PP) on the latter complications remains relatively unknown.

OBJECTIVES: To explore whether high intraoperative PP values are associated with postoperative AKI.

MATERIAL AND METHODS: The data for this study come from a prospective cohort study in which patients who underwent abdominal surgery between October 1, 2018 and July 15, 2019 in university hospital in Katowice, Poland were included in the analysis. Preand intraoperative data, including blood pressure measurements, were acquired from medical charts. Several PP thresholds were applied: >50, >55, >60, >65, >70, >75, >80, >85, and >90 mm Hg. Additionally, by analyzing the maximal PP during the procedures, the cutoff point for the occurrence of outcomes was estimated. Postoperative AKI was considered as the outcome of the study. Univariable and multivariable analyses were performed to assess PP relationship with AKI.

RESULTS: Four hundred and ninety-four patients were included in the analysis. The AKI was present in 32 (6.5%) cases. The receiver operating characteristic (ROC) curve analysis estimated a cutoff point of >84 mm Hg of maximal PP to be associated with the outcome. The PP values above 80 mm Hg and onward were successfully included in the multivariable statistical models. A model in which PP > 90 mm Hg (odds ratio (OR) = 4.03; 95% confidence interval (95% CI): [1.53; 10.62]) was included, had the best predicting value in predicting hypoperfusion injury (area under the receiver operating characteristics (AUROC) = 0.88). Apart from PP, intraoperative hypotension, presence of chronic arterial hypertension, chronic kidney disease, and procedure duration were independently associated with AKI.

CONCLUSIONS: High intraoperative PP may be associated with the occurrence of postoperative AKI. However, the effect of high PP should be confirmed in other noncardiac populations to prove the generalizability of our results.

PMID:35166075 | DOI:10.17219/acem/145946

Adv Clin Exp Med. 2022 Feb 15. doi: 10.17219/acem/131961. Online ahead of print.

ABSTRACT

BACKGROUND: The production of inflammatory mediators is critical for tenocytes proliferation and migration, which play an important role in rotator cuff injury repair and regulation of collagen. MicroRNA (miRNA)-205 (miR-205) promotes the secretion of inflammatory factors. The mechanism of the tenocytes regulation by miR-205 remains unknown. In this paper, we showed that miR-205 can regulate the proliferation, migration and fibrosis of tenocytes.

OBJECTIVES: To investigate the function and mechanism of miR-205/MeCP2 pathway on the proliferation, migration and fibrosis of rotator cuff tenocytes, in order to provide a new perspective on the repair of rotator cuff tear injury.

MATERIAL AND METHODS: The tenocytes were collected under sterile conditions from the Achilles tendons of Sprague Dawley (SD) rats (weighing 150-200 g). The cells of passages 2-4 were used for the following experiments. All miRNA and vectors were transfected with Lipofectamine 2000. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR), Cell Counting Kit-8 (CCK-8) assay, luciferase reporter assay, and migration assay were performed. Then, immunoblotting analysis and statistical analysis were conducted.

RESULTS: The CCK-8 and migration assay revealed that miR-205 inhibition resulted in increased tenocytes proliferation, migration and fibrosis. The miR-205 reduced the mRNA and protein expression levels of MECP2, which is involved in cell proliferation and migration of tenocytes. The miR-205 inhibited luciferase intensity under the control of the 3’UTRs of MECP2.

CONCLUSIONS: The inhibition of MECP2 reversed the effect of miR-205 inhibitor on tenocytes, including the proliferation and migration of tenocytes, indicating that miR-205 may be valuable in miRNA-based therapies for rotator cuff injury.

PMID:35166074 | DOI:10.17219/acem/131961

ESC Heart Fail. 2022 Feb 15. doi: 10.1002/ehf2.13841. Online ahead of print.

ABSTRACT

AIMS: The effects of inhibition of sodium glucose cotransporter (SGLT)-1, as opposed to SGLT2, on cardiovascular structure and function are not well known. We assessed the associations of a missense genetic variant of SGLT1 with cardiac structure and function.

METHODS AND RESULTS: We evaluated associations of a functionally modifying variant of SLC5A1 (rs17683011 [p.Asn51Ser]), the gene that encodes SGLT1, with cardiac structure and function on echocardiography among middle-aged adults in the Coronary Artery Risk Development in Young Adults Study. Of 1904 participants (55.3 ± 3.5 years, 57% female, 34% Black), 166 (13%) White participants and 18 (3%) Black participants had at least one copy of rs17683011. There were no significant differences in age, sex, body mass index, glucose, or diabetes status by the presence of the rs17683011 variant. In Black participants, the presence of at least one copy of the rs17683011 variant was significantly associated with better GLS compared with those without a copy of the variant after covariate adjustment (-15.8 ± 0.7% vs. -14.0 ± 0.1%, P = 0.02). Although the direction of effect was consistent, the association between the presence of at least one copy of rs17683011 and GLS was not statistically significant in White participants (-15.1 ± 0.2% vs. -14.8 ± 0.1%, P = 0.16). There were no significant associations between rs17683011 and other measures of LV structure, systolic function, or diastolic function.

CONCLUSIONS: The rs17683011 variant, a functionally modifying variant of the SGLT1 gene, was associated with higher GLS among middle-age adults. These exploratory findings require further validation and suggest that SGLT1 inhibition may have beneficial effects upon LV systolic function.

PMID:35166069 | DOI:10.1002/ehf2.13841

Cancer Med. 2022 Feb 15. doi: 10.1002/cam4.4548. Online ahead of print.

ABSTRACT

BACKGROUND: While the excess in lung cancer risk among lower socioeconomic status individuals has been widely described, the magnitude of this association across lung cancer subtypes, as well as histotype-related long-term incidence trends, are inconclusively reported.

AIMS: We explored the variation in the incidence of the three main lung cancer histotypes (i.e. squamous cell carcinoma, small cell carcinoma and adenocarcinoma) by socioeconomic status (SES, i.e. upper and lower white collar, upper and lower blue collar, and farming/forestry/fishing) in the adult population of four Nordic countries (i.e. Sweden, Norway, Finland and Denmark).

MATERIALS & METHODS: We have used data from the Nordic Occupational Cancer Study (NOCCA), computing age-standardized incidence rates per 100,000 person-years truncated at ages 50-69 years, by sex, histotype, country and SES, for the period 1971-2005. We estimated relative risks and the corresponding 95% confidence intervals through Poisson regression models, including terms for SES, age, sex and country, as indicated.

RESULTS: A clear socioeconomic gradient, with a progressive increase in lung cancer risk as SES level decreases, was observed in all subtypes and in both sexes. Favourable lung cancer incidence trends were seen among men for squamous cell and small cell carcinomas, although for adenocarcinomas rates were increasing everywhere except for Finland. Among women, upward temporal trends were seen in all SES groups and for all subtypes, although rates increased to a greater extent for low, compared to high, SES, especially in Denmark and Norway. Farmers showed comparatively lower risks compared to other SES categories.

DISCUSSION: This prospective cohort study shows that substantial socioeconomic inequalities in the incidence of the most important lung cancer histotypes exist in the Nordic Countries, and that these inequalities are on the rise, especially among women.

CONCLUSION: Smoking habits are likely to largely explain the observed social gradient for lung cancer histotypes in both sexes.

PMID:35166068 | DOI:10.1002/cam4.4548

Adv Sci (Weinh). 2022 Feb 15:e2105179. doi: 10.1002/advs.202105179. Online ahead of print.

ABSTRACT

Emerging protein-protein interaction (PPI) modulators have brought out exciting ability as therapeutics in human diseases, but its clinical translation has been greatly hampered by the limited affinity. Inspired by the homodimerize structure of antibody, the homodimerization contributes hugely to generating the optimized affinity is conjectured. Herein, a statistical-mechanics-theory-guided method is established to quantize the affinity of ligands with different topologies through analyzing the change of enthalpy and the loss of translational and rotational entropies. A peptide modulator for p53-MDM2 termed CPAP is used to homodimerize connecting, and this simple homodimerization can significantly increase the affinity. To realize the cellular internalization and tumor accumulation, ^Dimer CPAP and ^Mono CPAP are nanoengineered into gold(I)-CPAP supermolecule by the aurophilic interaction-driven self-assembly. Nano-^Dimer CPAP potently suppressed tumor growth in lung cancer allograft model and a patient-derived xenograft model in more action than Nano-^Mono CPAP, while keeping a favorable drug safety profile. This work not only presents a physico-mechanical method for calculating the affinity of PPI modulators, but also provides a simple yet robust homodimerization strategy to optimize the affinity of PPI modulators.

PMID:35166067 | DOI:10.1002/advs.202105179