Category: Nevin Manimala

PNAS Nexus. 2022 Sep 4;1(4):pgac176. doi: 10.1093/pnasnexus/pgac176. eCollection 2022 Sep.

ABSTRACT

The purpose of this study was to compare basketball performance markers 1 y prior to initial severe lower extremity injury, including ankle, knee, and hip injuries, to 1 and 2 y following injury during the regular National Basketball Association (NBA) season. Publicly available data were extracted through a reproducible extraction computed programmed process. Eligible participants were NBA players with at least three seasons played between 2008 and 2019, with a time-loss injury reported during the study period. Basketball performance was evaluated for season minutes, points, and rebounds. Prevalence of return to performance and linear regressions were calculated. A total of 285 athletes sustained a severe lower extremity injury. A total of 196 (69%) played for 1 y and 130 (45%) played for 2 y following the injury. A total of 58 (30%) players participated in a similar number of games and 57 (29%) scored similar points 1 y following injury. A total of 48 (37%) participated in a similar number of games and 55 (42%) scored a similar number of points 2 y following injury. Fewer than half of basketball players who suffered a severe lower extremity injury were participating at the NBA level 2 y following injury, with similar findings for groin/hip/thigh, knee, and ankle injuries. Fewer than half of players were performing at previous preinjury levels 2 y following injury. Suffering a severe lower extremity injury may be a prognostic factor that can assist sports medicine professionals to educate and set performance expectations for NBA players.

PMID:36714864 | PMC:PMC9802060 | DOI:10.1093/pnasnexus/pgac176

PNAS Nexus. 2022 Sep 14;1(4):pgac154. doi: 10.1093/pnasnexus/pgac154. eCollection 2022 Sep.

ABSTRACT

We present a data-driven approach to characterizing nonidentifiability of a model’s parameters and illustrate it through dynamic as well as steady kinetic models. By employing Diffusion Maps and their extensions, we discover the minimal combinations of parameters required to characterize the output behavior of a chemical system: a set of effective parameters for the model. Furthermore, we introduce and use a Conformal Autoencoder Neural Network technique, as well as a kernel-based Jointly Smooth Function technique, to disentangle the redundant parameter combinations that do not affect the output behavior from the ones that do. We discuss the interpretability of our data-driven effective parameters, and demonstrate the utility of the approach both for behavior prediction and parameter estimation. In the latter task, it becomes important to describe level sets in parameter space that are consistent with a particular output behavior. We validate our approach on a model of multisite phosphorylation, where a reduced set of effective parameters (nonlinear combinations of the physical ones) has previously been established analytically.

PMID:36714862 | PMC:PMC9802152 | DOI:10.1093/pnasnexus/pgac154

PNAS Nexus. 2022 Aug 27;1(4):pgac169. doi: 10.1093/pnasnexus/pgac169. eCollection 2022 Sep.

ABSTRACT

Routing choices of walking pedestrians in geometrically complex environments are regulated by the interplay of a multitude of factors such as local crowding, (estimated) time to destination, and (perceived) comfort. As individual choices combine, macroscopic traffic flow patterns emerge. Understanding the physical mechanisms yielding macroscopic traffic distributions in environments with complex geometries is an outstanding scientific challenge, with implications in the design and management of crowded pedestrian facilities. In this work, we analyze, by means of extensive real-life pedestrian tracking data, unidirectional flow dynamics in an asymmetric setting, as a prototype for many common complex geometries. Our environment is composed of a main walkway and a slightly longer detour. Our measurements have been collected during a dedicated high-accuracy pedestrian tracking campaign held in Eindhoven (The Netherlands). We show that the dynamics can be quantitatively modeled by introducing a collective discomfort function, and that fluctuations on the behavior of single individuals are crucial to correctly recover the global statistical behavior. Notably, the observed traffic split substantially departs from an optimal, transport-wise, partition, as the global pedestrian throughput is not maximized.

PMID:36714860 | PMC:PMC9802426 | DOI:10.1093/pnasnexus/pgac169

PNAS Nexus. 2022 Sep 1;1(4):pgac181. doi: 10.1093/pnasnexus/pgac181. eCollection 2022 Sep.

ABSTRACT

SARS-CoV-2 continues to evolve, causing waves of the pandemic. Up to May 2022, 10 million genome sequences have accumulated, which are classified into five major variants of concern. With the growing number of sequenced genomes, analysis of the big dataset has become increasingly challenging. Here we developed systematic approaches based on sets of correlated single nucleotide variations (SNVs) for comprehensive subtyping and pattern recognition of transmission dynamics. The approach outperformed single-SNV and spike-centric scans. Moreover, the derived subtypes elucidate the relationship of signature SNVs and transmission dynamics. We found that different subtypes of the same variant, including Delta and Omicron exhibited distinct temporal trajectories. For example, some Delta and Omicron subtypes did not spread rapidly, while others did. We identified sets of characteristic SNVs that appeared to enhance transmission or decrease efficacy of antibodies for some subtypes. We also identified a set of SNVs that appeared to suppress transmission or increase viral sensitivity to antibodies. For the Omicron variant, the dominant type in the world, we identified the subtypes with enhanced and suppressed transmission in an analysis of eight million genomes as of March 2022 and further confirmed the findings in a later analysis of ten million genomes as of May 2022. While the “enhancer” SNVs exhibited an enriched presence on the spike protein, the “suppressor” SNVs are mainly elsewhere. Disruption of the SNV correlation largely destroyed the enhancer-suppressor phenomena. These results suggest the importance of fine subtyping of variants, and point to potential complex interactions among SNVs.

PMID:36714842 | PMC:PMC9802201 | DOI:10.1093/pnasnexus/pgac181

PNAS Nexus. 2022 Aug 27;1(4):pgac174. doi: 10.1093/pnasnexus/pgac174. eCollection 2022 Sep.

ABSTRACT

The instability of human bipedalism demands that the brain accurately senses balancing self-motion and determines whether movements originate from self-generated actions or external disturbances. Here, we challenge the longstanding notion that this process relies on a single representation of the body and world to accurately perceive postural orientation and organize motor responses to control balance self-motion. Instead, we find that the conscious sense of balance can be distorted by the corrective control of upright standing. Using psychophysics, we quantified thresholds to imposed perturbations and balance responses evoking cues of self-motion that are (in)distinguishable from corrective balance actions. When standing immobile, participants clearly perceived imposed perturbations. Conversely, when freely balancing, participants often misattributed their own corrective responses as imposed motion because their balance system had detected, integrated, and responded to the perturbation in the absence of conscious perception. Importantly, this only occurred for perturbations encoded ambiguously with balance-correcting responses and that remained below the natural variability of ongoing balancing oscillations. These findings reveal that our balance system operates on its own sensorimotor principles that can interfere with causal attribution of our actions, and that our conscious sense of balance depends critically on the source and statistics of induced and self-generated motion cues.

PMID:36714829 | PMC:PMC9802180 | DOI:10.1093/pnasnexus/pgac174

Popul Space Place. 2022 Oct 27:e26. doi: 10.1002/psp.2626. Online ahead of print.

ABSTRACT

Despite anecdotal evidence of a COVID-19 induced decline in the intensity of interstate migration in Australia, population-level evidence is limited. The recent release of the 2020 wave of the Household, Income and Labour Dynamics in Australia (HILDA) Survey provides a unique opportunity to robustly assess the effect of the COVID-19 pandemic on the level, direction, determinants, and reasons for migration in Australia. By applying a series of regression models to individual-level longitudinal microdata, and measuring migration at a range of spatial scales, this paper shows that COVID-19 has somewhat accelerated the long-term decline in the intensity of internal migration-particularly for residential mobility, short-distance migration, and migration due to employment and involuntary reasons. The socio-demographic determinants of migration have remained broadly stable, despite a slight increase in the deterring effect of duration of residence and a reduction in the impact of education. Finally, we show that the increase in net migration gains in regional areas is underpinned by a decrease in outflows. Juxtaposing these results with aggregate-level migration statistics from the Australian Bureau of Statistics from 2021, we conclude that the effect of COVID-19 on internal migration to date has been minimal and is likely to be short-lived. However, it may still be too soon to make a definitive judgement, as shifts in work patterns stemming from the pandemic may further transform the level, direction, and composition of internal migration.

PMID:36714823 | PMC:PMC9874503 | DOI:10.1002/psp.2626

Contemp Clin Trials Commun. 2023 Jan 21:101070. doi: 10.1016/j.conctc.2023.101070. Online ahead of print.

ABSTRACT

BACKGROUND: The objective of the study was to evaluate the effect of Colchicine 0.5 mg. and Aspirin 75 mg. oral tablets given together on management of moderate COVID-19.

METHODS: The study was carried out in 122 moderate COVID-19 patients between ages 40-80 years in hospital, instructed to take either 1 tablet of Colchicine 0.5 mg. and Aspirin 75 mg. each (treatment group), or 1 tablet of Aspirin 75 mg (Control group), twice a day along with standard of care.

RESULT: At the end of treatment, reduction was seen in the treatment group in score of 8-point ordinal scale, troponin, D-Dimer, Hs-CRP from baseline. There was a fall of 51.1% among control arm and 53.4% among treatment arm in 8-point ordinal score. The reduction in mean D-Dimer was 37% in control group and 38.1% in treatment group. The mean reduction in CT severity score in control group was 3.65 and in treatment group was 4.82, and the difference between the two groups was statistically significant (P value = 0.018).

CONCLUSION: It was evident from CT scan scores that the treatment group has shown significant improvement in the reduction of inflammation and other COVID-19 symptoms as compared to the control group. The fall in Ferritin, Hs-CRP and D-Dimer level after treatment were indicative of improvement in internal inflammatory response of body in COVID-19 disease. As increased troponin levels indicate some degree of heart damage, the fall in troponin levels indicated that test treatment improved heart health in COVID-19 patients.

PMID:36714812 | PMC:PMC9862705 | DOI:10.1016/j.conctc.2023.101070

BMC Musculoskelet Disord. 2023 Jan 30;24(1):77. doi: 10.1186/s12891-023-06167-6.

ABSTRACT

PURPOSE: To evaluate the outcomes of distal femoral, proximal tibial, and distal tibial physeal bar resection combined with or without the Hemi-Epiphysiodesis procedure and provide a better understanding of the application of physeal bar resection combined with Hemi-Epiphysiodesis procedure in the treatment of physeal bar growth arrest.

METHODS: We retrospectively reviewed the patients who suffered physeal bar and underwent physeal bar resection with or without the Hemi-Epiphysiodesis technique during 2010-2020. All were followed up for at least 2 years or to maturity. A modified mapping method was used to determine the area of a physeal bar by CT data. The aLDFA, aMPTA, aLDTA, MAD, and LLD were measured to assess the deformity of the lower limb.

RESULTS: In total, 19 patients were included in this study. The average age was 8.9 years (range 4.4 to 13.3 years old). During the follow-up, 4 (21.1%) patients had an angular change < 5°; 12 (63.2%) patients had angular deformity improvement > 5° averaging 10.0° (range 5.3° to 23.2°), and 3 (15.8%) patients had improvement of the angular deformity averaging 16.8° (range 7.4° to 27.1°). Eleven patients (57.9%) had significant MAD improvement. After surgery, we found that 7 (36.8%) patients had an LLD change of < 5 mm and were considered unchanged. Only 2 (15%) patients had an LLD improvement > 5 mm averaging 1.0 cm (range 0.7 to 1.3 cm), and 7 (36.8%) patients had increasing of LLD > 5 mm averaging 1.3 cm (range 0.5 to 2.5 cm). There were no postoperative fractures, infections, or intraoperative complications such as neurovascular injury.

CONCLUSION: Physeal bar resection combined with Hemi-epiphysiodesis is helpful for partial epiphysis growth arrest. Without statistically verifying, we still believe that patients with limited growth ability could benefit more from physeal bar resection combined with Hemi-epiphysiodesis.

PMID:36710347 | DOI:10.1186/s12891-023-06167-6

J Transl Med. 2023 Jan 29;21(1):54. doi: 10.1186/s12967-022-03843-4.

ABSTRACT

BACKGROUND: Clear cell sarcomas (CCSs) are translocated aggressive malignancies, most commonly affecting young adults with a high incidence of metastases and a poor prognosis. Research into the disease is more feasible when adequate models are available. By establishing CCS cell lines from a primary and metastatic lesion and isolating healthy fibroblasts from the same patient, the in vivo process is accurately reflected and aspects of clinical multistep carcinogenesis recapitulated.

METHODS: Isolated tumor cells and normal healthy skin fibroblasts from the same patient were compared in terms of growth behavior and morphological characteristics using light and electron microscopy. Tumorigenicity potential was determined by soft agar colony formation assay and in vivo xenograft applications. While genetic differences between the two lineages were examined by copy number alternation profiles, nuclear magnetic resonance spectroscopy determined arginine methylation as epigenetic features. Potential anti-tumor effects of a protein arginine N-methyltransferase type I (PRMT1) inhibitor were elicited in 2D and 3D cell culture experiments using cell viability and apoptosis assays. Statistical significance was calculated by one-way ANOVA and unpaired t-test.

RESULTS: The two established CCS cell lines named MUG Lucifer prim and MUG Lucifer met showed differences in morphology, genetic and epigenetic data, reflecting the respective original tissue. The detailed cell line characterization especially in regards to the epigenetic domain allows investigation of new innovative therapies. Based on the epigenetic data, a PRMT1 inhibitor was used to demonstrate the targeted antitumor effect; normal tissue cells isolated and immortalized from the same patient were not affected with the IC₅₀ used.

CONCLUSIONS: MUG Lucifer prim, MUG Lucifer met and isolated and immortalized fibroblasts from the same patient represent an ideal in vitro model to explore the biology of CCS. Based on this cell culture model, novel therapies could be tested in the form of PRMT1 inhibitors, which drive tumor cells into apoptosis, but show no effect on fibroblasts, further supporting their potential as promising treatment options in the combat against CCS. The data substantiate the importance of tailored therapies in the advanced metastatic stage of CCS.

PMID:36710341 | DOI:10.1186/s12967-022-03843-4

BMC Womens Health. 2023 Jan 30;23(1):39. doi: 10.1186/s12905-023-02180-y.

ABSTRACT

BACKGROUND: In Ethiopia high population growth and unintended pregnancies are posing pressures where the economy is incapable of holding overpopulation. Despite this problem, utilization of modern contraception is low in rural areas of the country, especially in the areas where polygamy is common. Therefore, this study was conducted to assess contraceptive utilization and associated factors among polygamous and monogamous women in, Ethiopia.

METHOD: A community-based comparative cross-sectional and phenomenological study design was employed from July 1 to September 30, 2021, on the total sample size of 774 selected married women of the reproductive age group by using a multistage sampling method and a purposive sampling method were used for the qualitative part of the study. A pre-tested interview with a structured questionnaire was used to collect data and key informants were interviewed using semi-structured questionnaire. Associated factors were analyzed by using bivariable and multivariable binary logistic regression models. The odds ratio, with a 95% confidence level, was used to declare a statistically significant association.

RESULT: A total of 703 married women of the reproductive age groups were interviewed, yielding a 90.89% response rate; among these married women, 352 and 351 were in monogamous and polygamous relationships. The proportion of women who use modern contraceptives was 161 (45.7%) in monogamous relationship, and 151 (43.0%) in polygamous relationships. Overall, utilization of modern contraceptives was significantly associated with educational status (AOR = 2.143, CI:1.428-3.216), religion (AOR = 1.704, CI: 1.144-2.539), undesired fertility (AOR = 3.17,CI:1.939-5.183), who decides on the number of children (AOR = 3.054, CI:1.93-4.832), getting clear information by Health care provider (AOR = 4.624, CI:3.132-6.828), family pressure (AOR = 1.855, CI:1.351-2.75), fear of social stigma (AOR = 2.482, CI:1.666-3.699), and accepts myths about contraceptives (AOR = 1.878, CI:1.278-2.761).

CONCLUSION: This study identified that utilization of modern contraception was low in the study area. The district health office and concerned stakeholders should implement interventions that scale up contraceptive use, need family involvement in decision making, addressing myths around contraceptives, helping women to get education, and training of health care providers.

PMID:36710331 | DOI:10.1186/s12905-023-02180-y