Nevin Manimala

Biol Cybern. 2022 Oct 27. doi: 10.1007/s00422-022-00948-3. Online ahead of print.

ABSTRACT

The visual systems of insects are relatively simple compared to humans. However, they enable navigation through complex environments where insects perform exceptional levels of obstacle avoidance. Biology uses two separable modes of optic flow to achieve this: rapid gaze fixation (rotational motion known as saccades); and the inter-saccadic translational motion. While the fundamental process of insect optic flow has been known since the 1950’s, so too has its dependence on contrast. The surrounding visual pathways used to overcome environmental dependencies are less well known. Previous work has shown promise for low-speed rotational motion estimation, but a gap remained in the estimation of translational motion, in particular the estimation of the time to impact. To consistently estimate the time to impact during inter-saccadic translatory motion, the fundamental limitation of contrast dependence must be overcome. By adapting an elaborated rotational velocity estimator from literature to work for translational motion, this paper proposes a novel algorithm for overcoming the contrast dependence of time to impact estimation using nonlinear spatio-temporal feedforward filtering. By applying bioinspired processes, approximately 15 points per decade of statistical discrimination were achieved when estimating the time to impact to a target across 360 background, distance, and velocity combinations: a 17-fold increase over the fundamental process. These results show the contrast dependence of time to impact estimation can be overcome in a biologically plausible manner. This, combined with previous results for low-speed rotational motion estimation, allows for contrast invariant computational models designed on the principles found in the biological visual system, paving the way for future visually guided systems.

PMID:36303043 | DOI:10.1007/s00422-022-00948-3

Nat Struct Mol Biol. 2022 Oct 27. doi: 10.1038/s41594-022-00844-1. Online ahead of print.

ABSTRACT

It is estimated that 10%-30% of disease-associated genetic variants affect splicing. Splicing variants may generate deleteriously altered gene product and are potential therapeutic targets. However, systematic diagnosis or prediction of splicing variants is yet to be established, especially for the near-exon intronic splice region. The major challenge lies in the redundant and ill-defined branch sites and other splicing motifs therein. Here, we carried out unbiased massively parallel splicing assays on 5,307 disease-associated variants that overlapped with branch sites and collected 5,884 variants across the 5′ splice region. We found that strong splice sites and exonic features preserve splicing from intronic sequence variation. Whereas the splice-altering mechanism of the 3′ intronic variants is complex, that of the 5′ is mainly splice-site destruction. Statistical learning combined with these molecular features allows precise prediction of altered splicing from an intronic variant. This statistical model provides the identity and ranking of biological features that determine splicing, which serves as transferable knowledge and out-performs the benchmarking predictive tool. Moreover, we demonstrated that intronic splicing variants may associate with disease risks in the human population. Our study elucidates the mechanism of splicing response of intronic variants, which classify disease-associated splicing variants for the promise of precision medicine.

PMID:36303034 | DOI:10.1038/s41594-022-00844-1

Nat Methods. 2022 Oct 27. doi: 10.1038/s41592-022-01640-x. Online ahead of print.

ABSTRACT

Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limited ability in analyzing the noncoding genome. We propose a computationally efficient and robust noncoding RV association detection framework, STAARpipeline, to automatically annotate a whole-genome sequencing study and perform flexible noncoding RV association analysis, including gene-centric analysis and fixed window-based and dynamic window-based non-gene-centric analysis by incorporating variant functional annotations. In gene-centric analysis, STAARpipeline uses STAAR to group noncoding variants based on functional categories of genes and incorporate multiple functional annotations. In non-gene-centric analysis, STAARpipeline uses SCANG-STAAR to incorporate dynamic window sizes and multiple functional annotations. We apply STAARpipeline to identify noncoding RV sets associated with four lipid traits in 21,015 discovery samples from the Trans-Omics for Precision Medicine (TOPMed) program and replicate several of them in an additional 9,123 TOPMed samples. We also analyze five non-lipid TOPMed traits.

PMID:36303018 | DOI:10.1038/s41592-022-01640-x

Nat Methods. 2022 Oct 27. doi: 10.1038/s41592-022-01644-7. Online ahead of print.

ABSTRACT

Neoantigens are the key targets of antitumor immune responses from cytotoxic T cells and play a critical role in affecting tumor progressions and immunotherapy treatment responses. However, little is known about how the interaction between neoantigens and T cells ultimately affects the evolution of cancerous masses. Here, we develop a hierarchical Bayesian model, named neoantigen-T cell interaction estimation (netie) to infer the history of neoantigen-CD8⁺ T cell interactions in tumors. Netie was systematically validated and applied to examine the molecular patterns of 3,219 tumors, compiled from a panel of 18 cancer types. We showed that tumors with an increase in immune selection pressure over time are associated with T cells that have an activation-related expression signature. We also identified a subset of exhausted cytotoxic T cells postimmunotherapy associated with tumor clones that newly arise after treatment. These analyses demonstrate how netie enables the interrogation of the relationship between individual neoantigen repertoires and the tumor molecular profiles. We found that a T cell inflammation gene expression profile (TIGEP) is more predictive of patient outcomes in the tumors with an increase in immune pressure over time, which reveals a curious synergy between T cells and neoantigen distributions. Overall, we provide a new tool that is capable of revealing the imprints left by neoantigens during each tumor’s developmental process and of predicting how tumors will progress under further pressure of the host’s immune system.

PMID:36303017 | DOI:10.1038/s41592-022-01644-7

Clin Psychol Psychother. 2022 Oct 27. doi: 10.1002/cpp.2795. Online ahead of print.

ABSTRACT

Baseline interpersonal problems have been associated with treatment outcome in eating disorders (ED) and are important for understanding ED maintenance and etiology. Despite this evidence, little is known about trajectories of change in interpersonal problems in the context of treatment, particularly in intensive ED treatment. This study examined the trajectory of total interpersonal problems in residential ED treatment, as well as two subdomains previously highlighted in ED research of being overly Cold (interpersonally distant) or overly Domineering (interpersonally controlling), as a function of different primary presenting ED diagnoses: anorexia nervosa restricting subtype (AN-R), binge-purge subtype (AN-BP), and bulimia nervosa or binge eating (BN/BED). Interpersonal problem data were collected at admission, discharge, and 6-month-follow-up. Trajectories were analyzed with multilevel models. Results showed small-to-medium statistically significant reductions in interpersonal problems across diagnostic groups from admission to discharge for total interpersonal scores, and gains appeared to be maintained at follow up for both AN groups. Patients diagnosed with primary AN experienced steeper declines in total interpersonal problems from admission to follow-up compared to patients diagnosed with BN/BED, with AN-R experiencing the steepest trajectory. Planned contrasts indicated anyone with relevant binge eating behaviors had higher average levels of both Cold, as well as Domineering problems. Exploratory contrasts suggested that patients who had more Domineering problems also exhibited more binge symptoms and were typically slower to improve. Overall, results suggest interpersonal problems are generally malleable in residential ED treatment, yet change patterns differ by presenting ED symptoms and interpersonal problem subdomain.

PMID:36303012 | DOI:10.1002/cpp.2795

Environ Sci Pollut Res Int. 2022 Oct 27. doi: 10.1007/s11356-022-23494-8. Online ahead of print.

ABSTRACT

Kinetics of the reaction of IO radicals with methanol (MeOH) and ethanol (EtOH) were experimentally studied in the gas phase using pulsed laser photolysis-cavity ring-down spectroscopy (PLP-CRDS). IO radicals were produced in situ at the reaction zone by photolysing a mixture of precursors (CH₃I + O₃ + N₂) at 248 nm and thereby electronically excited at 445.04 nm. The rate coefficients for the reactions of (IO + MeOH) and (IO + EtOH) were measured at a total pressure of 60 Torr/N₂ in the range of 258-360 K. At room temperature, the experimental rate coefficients of the title reactions were measured to be [Formula: see text] and [Formula: see text]. Dependencies of the kinetics with photolysis laser fluence and experimental pressures were verified. Effects of pressure over the kinetic behaviour of the studied systems were observed to be insignificant within the statistical uncertainties when studied in the range of ~ 30-150 Torr/N₂, whereas a minor and linear fluence dependency was observed within the studied limit. From the measured kinetic parameters, the atmospheric lifetimes of MeOH and EtOH were calculated in the tropospherically relevant conditions regarding their reactions with important atmospheric oxidants like Cl atom, OH and IO radicals. To complement experimental results, kinetics and thermochemistry for the title reactions were investigated theoretically via canonical variational transition state (CVT) theory in combination with small curvature tunnelling (SCT) corrections with a dual-level Interpolated Single Point Energy (ISPE) approach at the CCSD(T)/def2-QZVPP//M06-2X/def2-TZVPP level of theory/basis set in the temperatures between 200 and 400 K. Good degree of agreement was encountered between experimentally measured and theoretically calculated rate coefficients. This article also discusses the thermochemical parameters and kinetic branching ratios (BRs) of all the pathways involved in the title reactions.

PMID:36303003 | DOI:10.1007/s11356-022-23494-8

Aesthetic Plast Surg. 2022 Oct 27. doi: 10.1007/s00266-022-03151-8. Online ahead of print.

ABSTRACT

BACKGROUND: Dorsal preservation techniques have been preferred and gained popularity in recent years. The current study compares the effects of dorsal preservation and dorsal reduction rhinoplasty on nasal patency and aesthetic outcomes by using Patient-Reported Outcome Measures (PROMs) and rhinomanometry. To our knowledge, this is the first study to compare dorsal preservation and dorsal reduction techniques with rhinomanometry.

METHODS: This is a prospective study of 34 patients who underwent rhinoplasty between January 2021-June 2022. The patients were randomly selected preoperatively and divided into two groups as structural rhinoplasty (SR) and preservation rhinoplasty (PR). Nasal Obstruction and Symptom Evaluation (NOSE), Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) scales and rhinomanometric evaluation were performed preoperatively, at 3rd month and 12th month postoperatively.

RESULTS: Nineteen patients (10 female, 9 male) were in SR group, 15 patients (7 female, 8 male) were in PR group. There was not significant difference in terms of age and gender between groups. In both groups, NOSE, SCHNOS-O and SCHNOS-C results were found to be significantly lower at postoperative 3rd and 12th month compared to preoperatively (p < 0.001 for the entire SR group, p = 0.001 for the entire PR group). There was no significant difference between groups in terms of PROMs. Mean total nasal volume (TNV) at 12th month were statistically higher than preoperative value in PR group (p = 0.031). Also there was no significant difference in SR group and between groups in terms of rhinomanometry results.

CONCLUSION: Dorsal preservation with pushdown technique provides good functional and aesthetic results comparable with structural rhinoplasty.

LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . A well-designed prospective clinical trial.

PMID:36302983 | DOI:10.1007/s00266-022-03151-8

Aesthetic Plast Surg. 2022 Oct 27. doi: 10.1007/s00266-022-03134-9. Online ahead of print.

ABSTRACT

OBJECTIVE: To observe the clinical effect between orbital septum incision and classical incision of double eyelid plasty.

METHODS: We retrospectively analyzed 381 patients who underwent double eyelid blepharoplasty in the Department of Plastic and Laser Cosmetology of Hunan Provincial People’s Hospital from January 2019 to December 2019. The patients were divided into two groups according to different surgical methods: group A (n = 146) received the classical method and group B (n = 235) received the orbital septum method. The incidence of early postoperative complications, scar depression from 6 months to 1 year after the operation, the condition of ‘meat strip’ (the accumulation of soft tissue in front of the tarsal plate after double eyelid surgery, including skin, muscle, and fascia fat, results in a hypertrophic appearance of the upper eyelid) below the double eyelid line, and the symmetry of double eyelids were analyzed and evaluated.

RESULTS: The total number of early postoperative complications in group A was seven cases (incidence rate: approximately 4.80%), and the total number of early postoperative complications in group B was two cases (incidence rate: approximately 0.85%), with a statistically significant difference (P < 0.05). The degree of scar depression in group B was significantly lighter than that in group A from 6 months to 1 year after the operation (P < 0.05). The score of ‘meat strip’ below the double eyelid line in group B was significantly lighter than that in group A (P < 0.05). The symmetry of double eyelids in group B was better than that in group A (P < 0.05) CONCLUSION: Compared to the classical double eyelid method, the orbital septum method has the advantages of reducing early postoperative complications, reducing the severity of the scar, slighting the ‘meat strip,’ and improving symmetry, which results in higher postoperative satisfaction LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

PMID:36302980 | DOI:10.1007/s00266-022-03134-9

Sci Rep. 2022 Oct 27;12(1):18121. doi: 10.1038/s41598-022-23102-2.

ABSTRACT

Statins are hypolipidaemic in human immunodeficiency virus (HIV) positive individuals. However, their effect on all-cause mortality and rate of discontinuation is unclear. We conducted a systematic review to evaluate the impact of statins on all-cause mortality, discontinuation rates, and risk of adverse effects among HIV patients on highly active antiretroviral therapy (HAART). We searched four electronic databases from inception until October 2021 for trials and cohort studies evaluating the effects of statin treatment versus placebo in HIV patients. Forty-seven studies involving 91,594 patients were included. Statins were associated with significantly lower risk of discontinuation (RR, 0.701; 95% CI 0.508-0.967; p = 0.031). The risk of all-cause mortality (RR, 0.994; 95% CI 0.561-1.588; p = 0.827), any adverse effects (RR, 0.780; 95% CI 0.564-1.077; p = 0.131) and, diabetes mellitus (RR, 0.272; 95% CI 0.031-2.393; p = 0.241) with statin treatment were lower but not statistically significant compared to placebo/control. Statin treatment was associated with a trend of higher but statistically insignificant risk of myalgia (RR, 1.341; 95% CI 0.770-2.333; p = 0.299), elevated creatine kinase (RR, 1.101; 95% CI 0.457-2.651; p = 0.830) and liver enzyme activities (RR, 1.709; 95% CI 0.605-4.831; p = 0.312). Clinicians should consider the nocebo effect in the effective management of PLWH on statins, who present with common adverse effects such as myalgia and, elevated levels of creatine kinase and liver enzymes.

PMID:36302940 | DOI:10.1038/s41598-022-23102-2

Sci Rep. 2022 Oct 27;12(1):18108. doi: 10.1038/s41598-022-22816-7.

ABSTRACT

While understanding the time evolution of Covid-19 pandemic is needed to plan economics and tune sanitary policies, a quantitative information of the recurrent epidemic waves is elusive. This work describes a statistical physics study of the subsequent waves in the epidemic spreading of Covid-19 and disclose the frequency components of the epidemic waves pattern over two years in United States, United Kingdom and Japan. These countries have been taken as representative cases of different containment policies such as “Mitigation” (USA and UK) and “Zero Covid” (Japan) policies. The supercritical phases in spreading have been identified by intervals with RIC-index > 0. We have used the wavelet transform of infection and fatality waves to get the spectral analysis showing a dominant component around 130 days. Data of the world dynamic clearly indicates also the crossover to a different phase due to the enforcement of vaccination campaign. In Japan and United Kingdom, we observed the emergence in the infection waves of a long period component (~ 170 days) during vaccination campaign. These results indicate slowing down of the epidemic spreading dynamics due to the vaccination campaign. Finally, we find an intrinsic difference between infection and fatality waves pointing to a non-trivial variation of the lethality due to different gene variants.

PMID:36302922 | DOI:10.1038/s41598-022-22816-7