Distal Research Articles

Mediastinal staging lymph node probability map in non-small cell lung cancer

BackgroundMediastinal lymph node (LN) staging is routinely performed using PET/CT and EBUS-TBNA. Promising predictive algorithms for lymph nodes have been reported for each technique, both individually and in combination. This study aims to develop a predictive algorithm that combines EBUS, PET/CT and clinical data to provide a probability of malignancy.MethodsA retrospective study was conducted on consecutive patients with non-small cell lung carcinoma staged using PET/CT and EBUS-TBNA. Lymph nodes were identified by level (N1, N2, and N3) and anatomical region (AR) (subcarinal, paratracheal, and hilar). A Standardized Uptake Value (SUV) was determined for each sampled LN. The ultrasound features collected included diameter in the short axis (DSA), morphology, border, echogenicity and the presence of the vascular hilum. A robust logistic regression model was used to construct an algorithm to estimate the probability of malignancy of the lymph node.ResultsA total of 116 patients with a mean age of 66, 93% of whom were men, were included. 358 lymph nodes were evaluated, 51% of which exhibited adenocarcinoma and 35% were squamous, while 14% were classified as non-small-cell lung carcinoma. The model estimated the probability of malignancy for each lymph node using age, DSA, SUVmax, and AR. The Area Under the ROC curve, was 0.89. A user-friendly application was also developed (https://ubidi.shinyapps.io/lymma/.)ConclusionsThe integration of patient clinical characteristics, EBUS features, and PET/CT findings may generate a pre-sampling malignancy probability map for each lymph node. The model requires prospective and external validation.

Critical Shoulder Angle Measurement Accuracy in Magnetic Resonance Imaging versus Radiographs: A retrospective cross-sectional study

Background: The Critical Shoulder Angle (CSA) is a radiographic measurement that has proven valuable in assessing shoulder pathologies such as osteoarthritis and rotator cuff tears. Despite its clinical utility, the consistency of CSA measurements across different imaging modalities, particularly magnetic resonance imaging (MRI) versus radiographs, remains debated. Objective: This retrospective cross-sectional study aims to assess the accuracy and reliability of CSA measurements obtained from routine shoulder MRI compared to standard radiography. Methods: A total of 210 patients with both coronal oblique MRI images and true anteroposterior (AP) radiographs of the shoulder were included in the study. CSA measurements were independently performed by two observers using a standardized method, and inter- and intra-observer agreement was evaluated. Statistical analyses were conducted to determine differences in CSA measurements between the two modalities and assess agreement levels. Results: The mean CSA measured on radiographs (33.7 ± 4.4) was significantly higher than that on MRI (32.8 ± 4.06, p=0.04). Inter- and intra-observer agreements were higher for radiographic measurements (ICC > 0.95) compared to MRI, where variability was noted, particularly concerning gender differences. CSA values showed no significant differences based on shoulder side (right vs. left) in either modality. Conclusion: CSA measurements were more accurate and consistent on radiographs than MRI, suggesting that radiography remains the preferred modality for assessing CSA in clinical settings. The study highlights the need for standardized imaging techniques to improve measurement consistency across modalities.

Assessment of epicardial adipose tissue thickness as a novel cardiac risk factor in type 2 diabetic patients: a cross-sectional study

BackgroundThe incidence of type 2 diabetes mellitus is gradually growing with its negative impact on public health. Epicardial adipose tissue (EAT), as a visceral fat, is a source of many adipokines affecting the cardiovascular system. The goal of this investigation was to assess the EAT thickness as a cardiac risk factor in type 2 diabetics compared to nondiabetics along with its possible association with left ventricular diastolic function.A total of 100 subjects have been included in this investigation (50 subjects with type 2 diabetes and 50 controls). EAT thickness has been determined utilizing a transthoracic echocardiogram in the parasternal short and long axis views in front of the right ventricle-free wall at end-diastole along with an assessment of left ventricular diastolic function.ResultsThe investigation demonstrated that type 2 diabetic cases have a statistically significant greater EAT thickness than nondiabetic controls (P value < 0.001). EAT thickness was significantly correlated with the duration of T2DM and diastolic dysfunction even in the absence of cardiovascular history.ConclusionEAT thickness is higher among diabetic patients and is significantly related to the diabetes duration. Increased EAT thickness is related to diastolic dysfunction among diabetic than non-diabetic patients.

Lower vs upper extremity injection of agitated saline for identification of patent foramen ovale (LOCATE).

Upper extremity injection of agitated saline using echocardiography is standard for locating patent foramen ovale (PFO), but several studies found the lower extremity to be more sensitive. In this prospective study, patients were selected who had a prior embolic stroke of undetermined source by history and no PFO identified with transthoracic echocardiography. We placed intravenous access in the upper extremity and usedultrasound-guided access in the superficial greater saphenous vein in the lower extremity, evaluating best view and presence and size of PFO if found. On review of 910 subjects, twenty subjects completed the study. The average greater saphenous vein measured 0.49 ± 0.16 cm in diameter, and depth of 1.07 ± 0.66 cm. The apical four chamber view to visualize the atrial septum was considered superior (p < 0.005) to the subcostal and parasternal short axis views. A PFO was found in five of the twenty subjects with concordance among all readers via lower extremity injection, compared to four subjects via upper extremity injection. Lower extremity injection of contrast identified significantly (p < 0.05) larger PFO compared to upper extremity injection. Complications from greater saphenous vein access included one superficial thrombus, one vasovagal syncope and four with ecchymosis (all < 3cm). PFO are found significantly larger when utilizing the greater saphenous vein of the lower extremity compared to the upper extremity for injection of agitated saline andbest visualized with the apical four-chamber view.

Assessment of mandibular landmark specification: correspondence between two-dimensional radiography and three-dimensional computed tomography.

This study aimed to establish accurate correspondence between landmarks on lateral (LA) and posteroanterior (PA) cephalograms and to demonstrate the locational relationship of these landmarks in two-dimensional (2D) and three-dimensional (3D) images. Twenty patients with skeletal Class III jaw deformity, without significant facial asymmetry, were recruited for this study. LA and PA cephalograms, taken simultaneously just before the orthognathic surgery, were utilized. Twelve mandibular landmarks were identified on each cephalogram, and their 3D coordinates values, as well as the residual differences between LA and PA cephalograms were calculated. To clarify the geometric correspondence between the LA and PA landmarks, the epipolar line method was introduced, which aimed to reduce residuals. In addition, 3D coordinate values of landmarks were compared between cephalograms and CT images in five patients with minimal asymmetry, by measuring the distance between corresponding landmarks as an error metric. The use of epipolar lines significantly reduced the residuals for 3D coordinates across all landmarks compared to those without epipolar lines. In comparison of 3D coordinate values between cephalograms and CT images, the average error across all landmarks was approximately 0.64 mm, which was lower than reported in previous study. Incorporating epipolar lines during landmark extraction from LA and PA cephalograms significantly improved the accuracy and reliability of landmark correspondence between the two cephalograms. The 3D coordinate values derived from cephalograms closely matched those obtained from CT images, demonstrating high accuracy although they were independently derived.

Nearly complete late Eocene skull from the North Pacific elucidates the cranial morphology and affinities of the penguin-like Plotopteridae

The extinct Plotopteridae were penguin-like, wing-propelled diving birds of the North Pacific. Recently, the oldest and most complete plotopterid skull has been discovered in the late Eocene lower part of the Lincoln Creek Formation, southern Olympic Peninsula (Washington State, USA), and informs the poorly known cranial morphology of these birds. This skull is somewhat larger than previously described partial skulls from the Oligocene Pysht Formation of the northern Olympic Peninsula, from which it also differs in the shape of the nostrils. It may represent the genus Klallamornis, but a definitive taxonomic assignment is not yet possible. The specimen corroborates a sister group relationship of plotopterids to the suliform Suloidea and exhibits a notable character mosaic. Whereas the long rostrum most closely resembles that of the Fregatidae and some Phalacrocoracidae, the neurocranium is more similar to that of the Sulidae. An arcuate rostral ridge of the basicranium is otherwise only known from the Sphenisciformes, and a pair of prominent longitudinal ridges along the ventral surface of the rostrum is an autapomorphy of plotopterids. The small nostrils are situated at the caudal ends of conspicuous sulci, which are interpreted as vestiges of long, slit-like nostrils and are much less pronounced in extant Suliformes. Long, slit-like nostrils occur in stem group Sphenisciformes and may also have been present in stem group Fregatidae, in which case the nostrils were reduced twice within Suliformes, presumably to prevent salt water influx into the nasal cavity.

Neural induction: New insight into the default model and an extended four-step model in vertebrate embryos.

Neural induction is a process by which naïve ectodermal cells differentiate into neural progenitor cells through the inhibition of BMP signaling, a condition typically considered the "default" state in vertebrate embryos. Studies in vertebrate embryos indicate that active FGF/MAPK signaling reduces BMP signaling to facilitate neural induction. Consequently, I propose that FGF stimulation/BMP inhibition more accurately characterizes the default model. Initially, the neuroectoderm is instructed to differentiate into anterior forebrain tissue, with cranial signals stabilizing this outcome. Subsequently, a gradient of caudalizing signals converts the neuroectodermal cells into posterior midbrain, hindbrain, and spinal cord. Furthermore, at the caudal end of the embryo, neuromesodermal progenitor cells are destined to differentiate into both neural progenitor cells and mesodermal cells, aiding in body extension. In light of these observations, I suggest incorporating an additional step, elongation, into the conventional three-step model of neural induction. This updated model encompasses activation, stabilization, transformation, and elongation.

Intraoperative imaging adequacy and its impact on unplanned return-to-theatre rates in pedicle screw instrumentation

BACKGROUND Pedicle screw instrumentation is a critical technique in spinal surgery, offering effective stabilization for various spinal conditions. However, the impact of intraoperative imaging quality—specifically the use of both anteroposterior (AP) and lateral views—on surgical outcomes remains insufficiently studied. Evaluating whether the adequacy of these imaging modalities affects the risk of unplanned returns to theatre (URTT) within 90 days due to screw malplacement is essential for refining surgical practices and improving patient care. AIM To evaluate how intraoperative imaging adequacy influences unplanned return-to-theatre rates, focusing on AP and lateral fluoroscopic views. METHODS This retrospective cohort study analyzed 1335 patients who underwent thoracolumbar and sacral pedicle screw instrumentation between January 2013 and December 2022. Data on intraoperative imaging adequacy, screw placement, and URTT events were collected and statistically analyzed using IBM SPSS v23. Imaging adequacy was assessed based on the presence of both AP and lateral views, and outcomes were compared between imaging groups. RESULTS A total of 9016 pedicle screws were inserted, with 82 screws identified as malplaced in 52 patients. Of these, 46 patients required URTT due to screw malplacement, with 37 returning within 90 days (URTT90). Patients with both AP and lateral imaging saved intraoperatively had significantly lower URTT90 rates compared to those with only lateral imaging saved, demonstrating the critical role of imaging adequacy in improving surgical outcomes. CONCLUSION This study underscores that comprehensive intraoperative imaging with both AP and lateral views reduces unplanned returns, improves outcomes, enhances precision, and offers a cost-effective approach for better spinal surgery results.

Comparison of preoperative radiographic measurements for femoral shaft fractures: a study on canal diameter measurement methods.

This study sought to determine the most reliable preoperative method for measuring canal diameter in femoral shaft fractures to optimize intramedullary nailing outcomes. We retrospectively analyzed 164 patients treated with intramedullary nailing at University Hospital from October 2017 to December 2019. Each patient's canal diameter was measured using five techniques: simple anteroposterior (AP) radiography, simple lateral radiography, AP scanogram with a scano rod, lateral scanogram with a scano rod, and computed tomography (CT). Error was calculated as preoperative measurement minus actual nail diameter. Interobserver reliability was assessed with Cohen's Kappa coefficient and paired t tests, with subgroup analyses for isthmus fractures and osteoporosis. CT yielded the smallest error (-0.34 ± 0.87mm and 0.25 ± 1.39mm across observers), with Kappa values of 0.61-0.85 indicating substantial reliability. Only CT showed significant error differences for isthmus fractures (p < 0.05). No method differed significantly with osteoporosis (p > 0.05). Preoperative plans adjusted in 18% of scano rod cases due to discrepancies exceeding 2mm. CT offers the highest reliability, particularly for isthmus fractures, while scanograms outperform simple radiography, with AP views superior to lateral views. Further investigation is needed into osteoporosis effects on measurement accuracy.

Preseason Patellar Tendon Thickness Predicts Symptomatic Patellar Tendinopathy in Male NCAA Division I Basketball Players.

The purpose of this study was to evaluate whether increased anteroposterior (AP) thickness of the proximal patellar tendon at preseason evaluation is predictive of symptomatic patellar tendinopathy and associated sequelae. Thirty-one male National Collegiate Athletic Association (NCAA) Division I basketball players voluntarily participated in this study (n = 52 tendons from 27 athletes after application of exclusion criteria, with evaluation at preseason, midseason, and postseason time points). At each time point, Victorian Institute of Sport Assessment-Patellar Tendon (VISA-P) scores, patellar tendon tenderness, patellar tendon AP thickness, and the presence of a proximal patellar tendon hypoechoic region were evaluated. Measurement of patellar tendon AP thickness and the identification of hypoechoic regions were performed using a portable ultrasound device. Outcome measures included a proximal patellar tendon hypoechoic region, a trip to the training room (TTR), time-loss symptomatic patellar tendinopathy (TLPT), and patellar tendon rupture. Covariates evaluated in the multivariable regression model included body mass index and a patient-reported history of patellar tendinopathy (α = 0.05). The mean preseason tendon thickness was 4.78 ± 1.22 mm. Nine (17.3%) of the tendons were symptomatic to the point of requiring a TTR. Preseason tendon thickness was associated with increased odds of a TTR (adjusted odds ratio [aOR] = 3.68 [95% confidence interval (CI) = 1.73 to 7.81]; p < 0.01). The predicted probability of a TTR was 86.0% with a preseason tendon thickness of 8 mm versus 3.4% with a preseason tendon thickness of 4 mm. Preseason tendon thickness was also predictive of TLPT (aOR = 1.96 [95% CI = 1.03 to 3.71]; p = 0.04). Preseason VISA-P scores were not predictive of a TTR (p = 0.66) or TLPT (p = 0.60). Increased patellar tendon thickness on preseason ultrasound is predictive of symptomatic patellar tendinopathy and associated sequelae during an NCAA Division I basketball season. Ultrasound identification of at-risk individuals may allow triage toward additional physical therapy and activity modification for these athletes to prevent progression to irreversible patellar tendon disease. These data support the use of ultrasound as a screening tool for elite jumping athletes. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Increasing the acquisition speed in oblique plane microscopy via aliasing

Increasing the acquisition speed in oblique plane microscopy via aliasing

Silencing of β-catenin1 blocks tail regeneration, but does not induce head regeneration in the flatworm Macrostomum lignano

β-Catenin has two major functions conserved across metazoans. It enables the interaction of classical cadherin with actin and it is the main transcription factor activated by the canonical Wnt pathway. In these two functions, it acts in patterning of the major body axis in early embroys, in cell differentiation and proliferation. In flatworms, four β-catenin homologs have been identified in the planarian Schmidtea mediterranea. Functional studies revealed that only Smed-β-catenin1 can transduce the Wnt signal and plays a part in defining posterior identity. We made a phylogenetic reconstruction of β-catenin homologs retrieved from a wide range of flatworms and analysed the role of β-catenin during regeneration in Macrostomum lignano. We identified at least two copies of β-catenin in all major taxa except in Catenulida; this suggests that duplication of β-catenin occurred ancestrally in Rhabditophora. In M. lignano, we detected 3 β-catenin homologs. Upon knockdown of the 3 homologs, only Mlig-β-catenin1 blocked blastema formation and regeneration of a tail. After knockdown, posterior regenerates restored normal tails but with instances of imperfect or duplicated tails. Different to planarians, knockdown of Mlig-β-catenins individually or in combination failed to rescue a head in all amputation levels in anterior regenerates. Together, these findings suggest that β-catenin1 is responsible for posterior identity specification also in M. lignano. Our study demonstrates that the ability to rescue a head upon knockdown of β-catenin1 may be an apomorphy of planarians, but is not an ancestral character in flatworms.

Standardised Endoscopic Optic Nerve Decompression: A Comprehensive Radiological and Anatomical Study

Introduction: Despite expanding indications for endoscopic optic nerve decompression (EOND), uniform guidelines are lacking, resulting in variability in nerve exposure and hindering comparisons of treatment effectiveness. Aim: This study aims to propose a standardized approach for planning and performing EOND based on radiological and anatomical studies. Materials and methods: EOND was performed on fifteen freshly frozen cadaver heads using non-standard oblique reconstruction planes from computed tomography (CT) studies to trace the optic canal's circumference. The final decompression point was positioned a few millimeters posterior to the cranial end of the canal, where the nerve is surrounded by bone on 180 degrees of its circumference. After the transnasal procedure, transcranial access was used to verify the adequacy of the decompression. Results: The mean distances from the decompression endpoint to the orbital apex, cranial optic canal (OC) end, and lateral optico-carotid recess were 8.2 mm ±1.0, 3.0 mm ±1.1, and 0.4 mm ±0.8, respectively. In all 30 procedures, adequate coverage of the decompression was confirmed via the transcranial approach. Conclusions: Using non-standard oblique CT reconstruction planes allows for precise, individualized planning for EOND, reducing the risk of overly short or excessive decompression. Therefore, this method may be used to standardize the extent of optic nerve decompression performed using the endoscopic technique.

Genesis of the T-wave through various modes of ventricular recovery patterns using the equivalent dipole layer model.

The equivalent dipole layer (EDL) relates local endocardial and epicardial transmembrane potentials to body surface potentials and can therefore be used to gain insight into cardiac activation and recovery. To use the EDL-source model for the inverse problem of electrocardiography, initial estimates for local activation times (LAT) and recovery times (LRT) are required because of its non-linear relation with body surface potentials. To develop an AT-independent initial RT estimate in the EDL-source model. Body surface mapping (BSM) and cardiac imaging were performed in 15 subjects. LAT and LRT were estimated using the EDL-source model. Various ventricular recovery patterns were tested to investigate the relation between recovery patterns and normal T-waves, including LAT-dependent-recovery and RT differences along transmural, interventricular, anterior-posterior and apico-basal axes. A new algorithm was developed based on the backwards modeling of the T-wave (BackRep) to identify the latest area of recovery. Correlation coefficient (CC) and relative difference (RD) between the recorded and computed T-waves were reported. BackRep (CC=0.89 [IQR:0.83-0.90]; RD=0.63 [IQR:0.49-0.69]), outperformed the anatomical axes based recovery patterns (CC=0.29 [IQR:0.21-0.46] - 0.79 [IQR:0.78-0.83]; RD=1.02 [IQR:0.98-1.18] - 0.61 [IQR:0.57-0.68]) and LAT-based recovery pattern (CC=0.63 [IQR:0.60-0.73]; RD=4.35 [IQR:2.74-9.05]). Of the RT differences along the anatomical axes, the apico-basal recovery pattern showed the best match between recorded and computed T-waves. A significant apex-to-base RT difference was also found in the BackRep recovery maps. BackRep provides a reliable AT-independent initial RT estimate and supports the presence of an apex-to-base RT difference in normal T-wave morphology.

Optimizing the axis ratio of elliptical PCM encasement for enhanced thermal performance in radiant floor heating systems

With the rapid development of low-carbon buildings and energy-saving technologies, phase change materials (PCM) have been extensively applied in building floor heating systems due to their excellent thermal energy storage and temperature control characteristics. However, traditional encased PCM radiant floor heating systems (RFHS) exhibit drawbacks including slow thermal response, low thermal efficiency, and excessive structural layer thickness. This study proposes an innovative solution through CFD numerical simulation: replacing the conventional circular encasement with an elliptical encasement and optimizing the elliptical axis ratio to enhance the system’s thermal performance and reduce mortar layer thickness, thereby lowering construction costs. The study analyzes the thermal state of PCMs, temperature variations of the floor structure, and heat flux distribution. The results show that as the short axis (a) length of the elliptical encasement decreases, the floor’s thermal response becomes faster. When a = 1.5 times the radius of the hot water pipe, the floor achieves the optimal balance between thermal comfort and energy efficiency. Compared to the traditional design, this approach not only enhances thermal response speed and reduces energy consumption but also decreases the mortar layer thickness by 16.7%. This study provides a theoretical basis for optimizing RFHS integrated with PCMs and holds significant potential for engineering applications.

Microprism-based two-photon imaging of the mouse inferior colliculus reveals novel organizational principles of the auditory midbrain.

To navigate real-world listening conditions, the auditory system relies on the integration of multiple sources of information. However, to avoid inappropriate cross-talk between inputs, highly connected neural systems need to strike a balance between integration and segregation. Here, we develop a novel approach to examine how repeated neurochemical modules in the mouse inferior colliculus lateral cortex (LC) allow controlled integration of its multimodal inputs. The LC had been impossible to study via imaging because it is buried in a sulcus. Therefore, we coupled two-photon microscopy with the use of a microprism to reveal the first-ever sagittal views of the LC to examine neuronal responses with respect to its neurochemical motifs under anesthetized and awake conditions. This approach revealed marked differences in the acoustic response properties of LC and neighboring non-lemniscal portions of the inferior colliculus. In addition, we observed that the module and matrix cellular motifs of the LC displayed distinct somatosensory and auditory responses. Specifically, neurons in modules demonstrated primarily offset responses to acoustic stimuli with enhancement in responses to bimodal stimuli, whereas matrix neurons showed onset response to acoustic stimuli and suppressed responses to bimodal stimulation. Thus, this new approach revealed that the repeated structural motifs of the LC permit functional integration of multimodal inputs while retaining distinct response properties.

Metabolomic and molecular analysis reveals multiple pathways of TBBPA-induced developmental toxicity in zebrafish embryos.

Metabolomic and molecular analysis reveals multiple pathways of TBBPA-induced developmental toxicity in zebrafish embryos.

Temporal regulation of endoderm convergence and extension by the BMP activity gradient through mesoderm-dependent and independent mechanisms.

Temporal regulation of endoderm convergence and extension by the BMP activity gradient through mesoderm-dependent and independent mechanisms.

Impaired myocardial deformation and aortic distensibility by cardiac MRI in girls with Turner syndrome

Girls and women with Turner syndrome (TS) suffer from increased risk of cardiovascular diseases. We hypothesized that left ventricular (LV) myocardial strain and aortic elasticity will be impaired in girls with TS. Cardiac MRI of 45 girls with TS and 14 healthy control girls was performed. Tissue tracking was used to assess LV Global Longitudinal (GLS), circumferential (GCS), radial short and long axes (GRS SAX and GRS LAX) in patients compared to controls. Maximal and minimal aortic areas were measured in ascending aorta, proximal descending, and aorta at diaphragm. Regional strain and distensibility were calculated using previously validated formulas. Comparisons were made between patients with and without bicuspid aortic valve (BAV). Inter-observer agreement was assessed for myocardial strain and aortic strain and distensibility. Results of the study showed GLS was significantly impaired in TS patients − 15.6 ± 1.8% compared to the control group − 17.2 ± 1%, p value = 0.013. No significant differences were observed in other strain parameters. Aortic diameter was similar in patients and control groups. Ascending aorta strain and distensibility were significantly lower in TS patients (33 ± 19% and 9.1 ± 5.5 mm Hg− 1) compared to control group (55 ± 17% and 13.9 ± 4.9 10− 3 mm Hg− 1), p values 0.004 and 0.013. No significant differences were found in aortic strain and distensibility in the other 2 regions. No significant differences were observed between TS patients with and without BAV in myocardial strain and aortic strain and distensibility. Substantial to perfect inter-observer agreement was found for myocardial strain and aortic strain and distensibility. Cardiac MRI measurements of LV deformation and aortic function carry potential value as markers for early detection of myocardial and aortic disease in TS patients. Validation of the clinical impact and prognostic role require further longitudinal studies.

β-catenin-driven endomesoderm specification is a Bilateria-specific novelty

Endomesoderm specification by a maternal β-catenin signal and body axis patterning by interpreting a gradient of zygotic Wnt/β-catenin signalling was suggested to predate the split between Bilateria and their sister clade Cnidaria. However, in Cnidaria, the roles of β-catenin signalling in these processes have not been demonstrated directly. Here, by tagging the endogenous β-catenin in the cnidarian Nematostella vectensis, we confirm that its oral-aboral axis is indeed patterned by a gradient of β-catenin signalling. Strikingly, we show that, in contrast to bilaterians, Nematostella endomesoderm specification is repressed by β-catenin and takes place in the maternal nuclear β-catenin-negative part of the embryo. This completely changes the accepted paradigm and suggests that β-catenin-dependent endomesoderm specification was a bilaterian innovation linking endomesoderm specification to the subsequent posterior-anterior patterning.