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PLoS Computational Biology Aug 2023Over the past 40 years, there has been a strong focus on the development of mathematical models of angiogenesis, while developmental remodelling has received little such... (Review)
Review
Over the past 40 years, there has been a strong focus on the development of mathematical models of angiogenesis, while developmental remodelling has received little such attention from the mathematical community. Sprouting angiogenesis can be seen as a very crude way of laying out a primitive vessel network (the raw material), while remodelling (understood as pruning of redundant vessels, diameter control, and the establishment of vessel identity and hierarchy) is the key to turning that primitive network into a functional network. This multiscale problem is of prime importance in the development of a functional vasculature. In addition, defective remodelling (either during developmental remodelling or due to a reactivation of the remodelling programme caused by an injury) is associated with a significant number of diseases. In this review, we discuss existing mathematical models of developmental remodelling and explore the important contributions that these models have made to the field of vascular development. These mathematical models are effectively used to investigate and predict vascular development and are able to reproduce experimentally observable results. Moreover, these models provide a useful means of hypothesis generation and can explain the underlying mechanisms driving the observed structural and functional network development. However, developmental vascular remodelling is still a relatively new area in mathematical biology, and many biological questions remain unanswered. In this review, we present the existing modelling paradigms and define the key challenges for the field.
Topics: Humans; Vascular Remodeling; Models, Biological
PubMed: 37535698
DOI: 10.1371/journal.pcbi.1011130 -
Journal of Physical Therapy Science Sep 2023[Purpose] This study aimed to develop a clinical observation method to evaluate the position of the mass center. From the human visual capability, we considered it would...
[Purpose] This study aimed to develop a clinical observation method to evaluate the position of the mass center. From the human visual capability, we considered it would be practical to divide the body into two parts: the upper and the lower body mass. If we could identify their optimal position, we could observe the middle point in between as the center of mass. [Participants and Methods] Twenty healthy males performed forward bending, backward bending, squatting, and walking. The three-dimensional coordinates were analyzed using a conventional model. In addition, five "virtual" markers were assigned as upper and lower mass, respectively. The midpoints of each five virtual marker combinations defined the mass centers, providing 25 coordinates. We calculated the difference in the coordinates between mass centers from virtual markers and mass centers using a conventional model. The combination with the slightest error was evaluated to determine the 95% confidence interval of the observed points and whether the value was clinically beneficial. [Results] The optimal combination of the upper and lower mass was Th8 and in the middle of both hip and knee centers. [Conclusion] The overall magnitude of error was about 30 mm and enough to evaluate the center of mass with macroscopy.
PubMed: 37670758
DOI: 10.1589/jpts.35.638 -
Trends in Ecology & Evolution Apr 2024Advances in statistics mean that it is now possible to tackle increasingly sophisticated observation processes. The intricacies and ambitious scale of modern data... (Review)
Review
Advances in statistics mean that it is now possible to tackle increasingly sophisticated observation processes. The intricacies and ambitious scale of modern data collection techniques mean that this is now essential. Methodological research to make inference about the biological process while accounting for the observation process has expanded dramatically, but solutions are often presented in field-specific terms, limiting our ability to identify commonalities between methods. We suggest a typology of observation processes that could improve translation between fields and aid methodological synthesis. We propose the LIES framework (defining observation processes in terms of issues of Latency, Identifiability, Effort and Scale) and illustrate its use with both simple examples and more complex case studies.
Topics: Ecology; Research Design
PubMed: 37949794
DOI: 10.1016/j.tree.2023.10.009 -
BMC Urology Sep 2023Treatment decisions for localized prostate cancer must balance patient preferences, oncologic risk, and preservation of sexual, urinary and bowel function. While Active... (Review)
Review
BACKGROUND
Treatment decisions for localized prostate cancer must balance patient preferences, oncologic risk, and preservation of sexual, urinary and bowel function. While Active Surveillance (AS) is the recommended option for men with Grade Group 1 (Gleason Score 3 + 3 = 6) prostate cancer without other intermediate-risk features, men with Grade Group 2 (Gleason Score 3 + 4 = 7) are typically recommended active treatment. For select patients, AS can be a possible initial management strategy for men with Grade Group 2. Herein, we review current urology guidelines and the urologic literature regarding recommendations and evidence for AS for this patient group.
MAIN BODY
AS benefits men with prostate cancer by maintaining their current quality of life and avoiding treatment side effects. AS protocols with close follow up always allow for an option to change course and pursue curative treatment. All the major guideline organizations now include Grade Group 2 disease with slightly differing definitions of eligibility based on risk using prostate-specific antigen (PSA) level, Gleason score, clinical stage, and other factors. Selected men with Grade Group 2 on AS have similar rates of deferred treatment and metastasis to men with Grade Group 1 on AS. There is a growing body of evidence from randomized controlled trials, large observational (prospective and retrospective) cohorts that confirm the oncologic safety of AS for these men. While some men will inevitably conclude AS at some point due to clinical reclassification with biopsy or imaging, some men may be able to stay on AS until transition to watchful waiting (WW). Magnetic resonance imaging is an important tool to confirm AS eligibility, to monitor progression and guide prostate biopsy.
CONCLUSION
AS is a viable initial management option for well-informed and select men with Grade Group 2 prostate cancer, low volume of pattern 4, and no other adverse clinicopathologic findings following a well-defined monitoring protocol. In the modern era of AS, urologists have tools at their disposal to better stage patients at initial diagnosis, risk stratify patients, and gain information on the biologic potential of a patient's prostate cancer.
Topics: Male; Humans; Watchful Waiting; Neoplasm Grading; Quality of Life; Prospective Studies; Retrospective Studies; Prostatic Neoplasms; Prostate-Specific Antigen
PubMed: 37777716
DOI: 10.1186/s12894-023-01314-6 -
Acta Obstetricia Et Gynecologica... Sep 2023Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin (hCG) are often treated with methotrexate (MTX), but expectant management with close monitoring is a feasible alternative. Studies comparing the two treatments have not shown a statistically significant difference in uneventful resolution of ectopic pregnancy, but these studies were too small to define whether certain subgroups could benefit more from either treatment.
MATERIAL AND METHODS
We performed a systematic review and individual participant data meta-analysis (IPD-MA) of randomized controlled trials comparing systemic MTX and expectant management in women with tubal ectopic pregnancy and low hCG (<2000 IU/L). A one-stage IPD-MA was performed to assess overall treatment effects of MTX and expectant management to generate a pooled intervention effect. Subgroup analyses and exploratory multivariable analyses were undertaken according to baseline serum hCG and progesterone levels. Primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to <20 IU/L, or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Secondary outcomes were need for blood transfusion, surgical intervention, additional MTX side-effects and hCG resolution times.
TRIAL REGISTRATION NUMBER
PROSPERO: CRD42021214093.
RESULTS
1547 studies reviewed and 821 remained after duplicates removed. Five studies screened for eligibility and three IPD requested. Two randomized controlled trials supplied IPD, leading to 153 participants for analysis. Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (IPD risk ratio [RR] 1.16, 95% confidence interval [CI] 0.95-1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23-1.14). Mean time to success was 19.7 days (95% CI 17.4-22.3) after MTX and 21.2 days (95% CI 17.8-25.2) after expectant management (P = 0.25). MTX specific side-effects were reported in 33 MTX compared to four in the expectant group.
CONCLUSIONS
Our IPD-MA showed no statistically significant difference in treatment efficacy between MTX and expectant management in women with tubal ectopic pregnancy with low hCG. Initial expectant management could be the preferred strategy due to fewer side-effects.
Topics: Pregnancy; Humans; Female; Methotrexate; Watchful Waiting; Pregnancy, Tubal; Pregnancy, Ectopic; Chorionic Gonadotropin; Abortifacient Agents, Nonsteroidal; Retrospective Studies
PubMed: 37345445
DOI: 10.1111/aogs.14617 -
Ophthalmology Science 2024To assess whether the combination of OCT and OCT angiography (OCTA) can capture observable, but subtle, structural changes that precede clinically evident retinal...
PURPOSE
To assess whether the combination of OCT and OCT angiography (OCTA) can capture observable, but subtle, structural changes that precede clinically evident retinal neovascularization (RNV) in eyes with diabetic retinopathy (DR).
DESIGN
Retrospective, longitudinal study.
PARTICIPANTS
Patients with DR that had at least 2 visits.
METHODS
We obtained wide-field OCTA scans of 1 eye from each participant and generated OCT, OCTA, and cross-sectional OCTA. We identified eyes with RNV sprouts, defined as epiretinal hyperreflective materials on OCT with flow signals breaching the internal limiting membrane on the cross-sectional OCTA without recognizable RNV on OCTA and RNV fronds, defined as recognizable abnormal vascular structures on the OCTA. We examined the corresponding location from follow-up or previous visits for the presence or progression of the RNV.
MAIN OUTCOME MEASURES
The characteristics and longitudinal observation of early signs of RNV.
RESULTS
From 71 eyes, we identified RNV in 20 eyes with the combination of OCT and OCTA, of which 13 (65%) were photographically graded as proliferative DR, 6 (30%) severe nonproliferative DR, and 1 (5%) moderate nonproliferative diabetic retinopathy. From these eyes, we identified 38 RNV sprouts and 26 RNV fronds at the baseline. Thirty-four RNVs (53%) originated from veins, 24 (38%) were from intraretinal microabnormalities, and 6 (9%) were from a nondilated capillary bed. At the final visit, 53 RNV sprouts and 30 RNV fronds were detected. Ten eyes (50%) showed progression, defined as having a new RNV lesion or the development of an RNV frond from an RNV sprout. Four (11%) RNV sprouts developed into RNV fronds with a mean interval of 7.0 months. Nineteen new RNV sprouts developed during the follow-up, whereas no new RNV frond was observed outside an identified RNV sprout. The eyes with progression were of younger age ( = 0.014) and tended to be treatment naive ( = 0.07) compared with eyes without progression.
CONCLUSIONS
Longitudinal observation demonstrated that a combination of OCT and cross-sectional OCTA can identify an earlier form of RNV before it can be recognized on OCTA.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 37868804
DOI: 10.1016/j.xops.2023.100382 -
Progress in Neurobiology Dec 2023Classical neurophysiology suggests that the motor cortex (MI) has a unique role in action control. In contrast, this review presents evidence for multiple... (Review)
Review
Classical neurophysiology suggests that the motor cortex (MI) has a unique role in action control. In contrast, this review presents evidence for multiple parieto-frontal spinal command modules that can bypass MI. Five observations support this modular perspective: (i) the statistics of cortical connectivity demonstrate functionally-related clusters of cortical areas, defining functional modules in the premotor, cingulate, and parietal cortices; (ii) different corticospinal pathways originate from the above areas, each with a distinct range of conduction velocities; (iii) the activation time of each module varies depending on task, and different modules can be activated simultaneously; (iv) a modular architecture with direct motor output is faster and less metabolically expensive than an architecture that relies on MI, given the slow connections between MI and other cortical areas; (v) lesions of the areas composing parieto-frontal modules have different effects from lesions of MI. Here we provide examples of six cortico-spinal modules and functions they subserve: module 1) arm reaching, tool use and object construction; module 2) spatial navigation and locomotion; module 3) grasping and observation of hand and mouth actions; module 4) action initiation, motor sequences, time encoding; module 5) conditional motor association and learning, action plan switching and action inhibition; module 6) planning defensive actions. These modules can serve as a library of tools to be recombined when faced with novel tasks, and MI might serve as a recombinatory hub. In conclusion, the availability of locally-stored information and multiple outflow paths supports the physiological plausibility of the proposed modular perspective.
Topics: Humans; Parietal Lobe; Hand; Cognition
PubMed: 37832714
DOI: 10.1016/j.pneurobio.2023.102537 -
International Journal of Antimicrobial... Jan 2024The efficacy of BIC/FTC/TAF in HIV late presenters initiating antiretroviral therapy (ART) has not been sufficiently evaluated.
OBJECTIVES
The efficacy of BIC/FTC/TAF in HIV late presenters initiating antiretroviral therapy (ART) has not been sufficiently evaluated.
METHODS
The aim of this study was to assess the effectiveness and tolerability of BIC/FTC/TAF compared to other first-line antiretroviral regimens in treatment-naïve adult individuals from the CoRIS Cohort starting ART with CD4 counts <200 cells/mm and/or AIDS-defining conditions between January 1st 2019 and November 30th 2020. Logistic regression models were used to estimate odds ratios (ORs) of association between initial regimen and achievement of viral suppression (VS) (primary objective), defined as HIV RNA <50 cop/mL, and immunological recovery (IR) (secondary objective), defined as CD4 count >200 cells/mm, at weeks 24 and 48 after initiation of ART.
RESULTS
We evaluated 314 individuals (84.7% men, median age 40 years). Of them, 158 initiated with BIC/FTC/TAF. At inclusion, 117 had an AIDS-defining condition. In multivariable analyses, individuals with AIDS-defining conditions initiating ART with BIC/FTC/TAF achieved higher rates of VS at 24 weeks than other regimens (aOR: 0.2; 95% CI: 0.06-0.64) and, at 48 weeks, than DTG/ABC/3TC (aOR: 0.06; 95% CI: 0.01-0.76) and DTG + TDF/3TC (aOR: 0.2; 95% CI: 0.47-0.9). No other differences in VS or IR were observed. At 24 and 48 weeks after ART initiation, treatment discontinuations were lower with BIC/FTC/TAF than with other regimens (3.2% and 7.6% vs. 24.4% and 37.8%, respectively; P < 0.005).
CONCLUSION
Our results suggest that BIC/FTC/TAF could be a preferred regimen as initial therapy in HIV late presenters because of its high effectiveness and good tolerability.
Topics: Adult; Male; Humans; Female; Anti-HIV Agents; Acquired Immunodeficiency Syndrome; HIV Infections; Drug Combinations; Emtricitabine; Piperazines; Tenofovir; Pyridones; Alanine; Amides; Heterocyclic Compounds, 3-Ring
PubMed: 37890734
DOI: 10.1016/j.ijantimicag.2023.107016 -
Ultrasound in Obstetrics & Gynecology :... Nov 2023To assess whether coexisting fetal growth restriction (FGR) influences pregnancy latency among women with preterm pre-eclampsia undergoing expectant management....
OBJECTIVES
To assess whether coexisting fetal growth restriction (FGR) influences pregnancy latency among women with preterm pre-eclampsia undergoing expectant management. Secondary outcomes assessed were indication for delivery, mode of delivery and rate of serious adverse maternal and perinatal outcomes.
METHODS
We conducted a secondary analysis of the Pre-eclampsia Intervention (PIE) and the Pre-eclampsia Intervention 2 (PI2) trial data. These randomized controlled trials evaluated whether esomeprazole and metformin could prolong gestation of women diagnosed with pre-eclampsia between 26 and 32 weeks of gestation undergoing expectant management. Delivery indications were deteriorating maternal or fetal status, or reaching 34 weeks' gestation. FGR (defined by Delphi consensus) at the time of pre-eclampsia diagnosis was examined as a predictor of outcome. Only placebo data from PI2 were included, as the trial showed that metformin use was associated with prolonged gestation. All outcome data were collected prospectively from diagnosis of pre-eclampsia to 6 weeks after the expected due date.
RESULTS
Of the 202 women included, 92 (45.5%) had FGR at the time of pre-eclampsia diagnosis. Median pregnancy latency was 6.8 days in the FGR group and 15.3 days in the control group (difference 8.5 days; adjusted 0.49-fold change (95% CI, 0.33-0.74); P < 0.001). FGR pregnancies were less likely to reach 34 weeks' gestation (12.0% vs 30.9%; adjusted relative risk (aRR), 0.44 (95% CI, 0.23-0.83)) and more likely to be delivered for suspected fetal compromise (64.1% vs 36.4%; aRR, 1.84 (95% CI, 1.36-2.47)). More women with FGR underwent a prelabor emergency Cesarean section (66.3% vs 43.6%; aRR, 1.56 (95% CI, 1.20-2.03)) and were less likely to have a successful induction of labor (4.3% vs 14.5%; aRR, 0.32 (95% CI, 0.10-1.00)), compared to those without FGR. The rate of maternal complications did not differ significantly between the two groups. FGR was associated with a higher rate of infant death (14.1% vs 4.5%; aRR, 3.26 (95% CI, 1.08-9.81)) and need for intubation and mechanical ventilation (15.2% vs 5.5%; aRR, 2.97 (95% CI, 1.11-7.90)).
CONCLUSION
FGR is commonly present in women with early preterm pre-eclampsia and outcome is poorer. FGR is associated with shorter pregnancy latency, more emergency Cesarean deliveries, fewer successful inductions and increased rates of neonatal morbidity and mortality. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Infant, Newborn; Infant; Pregnancy; Female; Humans; Pregnancy Outcome; Cesarean Section; Pre-Eclampsia; Fetal Growth Retardation; Watchful Waiting; Metformin
PubMed: 37289938
DOI: 10.1002/uog.26282