Synthesis, preclinical evaluation and pilot clinical translation of [68Ga]Ga-PMD22, a novel nanobody PET probe targeting CLDN18.2 of gastrointestinal cancer.

PURPOSE: Claudin18.2 (CLDN18.2) is a novel target for diagnosis and therapy of gastrointestinal cancer. This study aimed to evaluate the safety and feasibility of a novel CLDN18.2-targeted nanobody, PMD22, labeled with gallium-68 ([68Ga]Ga), for detecting CLDN18.2 expression in patients with gastrointestinal cancer using PET/CT imaging. METHODS: [68Ga]Ga-PMD22 was synthesized based on the nanobody, and its cell binding properties were assayed. Preclinical pharmacokinetics were determined in CLDN18.2-positive xenografts using microPET/CT. Effective dosimetry of [68Ga]Ga-PMD22 was evaluated in 5 gastrointestinal cancer patients, and PET/CT imaging of [68Ga]Ga-PMD22 and [18F]FDG were performed head-to-head in 16 gastrointestinal cancer patients. Pathological tissues were obtained for CLDN18.2 immunohistochemical (IHC) staining and comparative analysis with PET/CT findings. RESULTS: Cell binding assay showed that [68Ga]Ga-PMD22 had a higher binding ability to AGSCLDN18.2 and BGC823CLDN18.2 cells than to AGS and BGC823 cells (p < 0.001). MicroPET/CT images showed that [68Ga]Ga-PMD22 rapidly accumulated in AGSCLDN18.2 and BGC823CLDN18.2 tumors, and high contrast tumor to background imaging was clearly observed. In the pilot study, the effective dose of [68Ga]Ga-PMD22 was 1.68E-02 ± 1.45E-02 mSv/MBq, and the CLDN18.2 IHC staining result was highly correlated with the SUVmax/BKGstomach of [68Ga]Ga-PMD22 (rs = 0.848, p < 0.01). CONCLUSION: A novel [68Ga]Ga-labeled nanobody probe targeting CLDN18.2, [68Ga]Ga-PMD22, was established and preliminarily proved to be safe and effective in revealing CLDN18.2-positive gastrointestinal cancer, providing a basis for the clinical translation of the agent. CLINICAL TRIAL REGISTRATION: This study was registered on the ClinicalTrials.gov (NCT05937919).

Generalizability of nociception level as a measure of intraoperative nociceptive stimulation: A retrospective analysis.

BACKGROUND: Nociception-guided intraoperative opioid administration might help reduce postoperative pain. A commonly used and validated nociception monitor system is nociception level (NOL), which provides the nociception index, ranging from 0 to 100, with 0 representing no nociception and 100 representing extreme nociception. We tested the hypothesis that NOL responses are similar in men and women given remifentanil and fentanyl, across various types of anesthesia, as a function of American Society of Anesthesiologists physical status designations, and over a range of ages and body morphologies. METHODS: We conducted a retrospective cohort analysis of trial data from eight prospective NOL validation studies. Among 522 noncardiac surgical patients enrolled in these studies, 447 were included in our analysis. We assessed NOL responses to various noxious and non-noxious stimuli. RESULTS: The average NOL in response to 315 noxious stimuli was 47 ± 15 (95% CI = 45-49). The average NOL in response to 361 non-noxious stimuli was 10 ± 12 (95% CI = 9-11). NOL responses were similar in men and women, in patients given remifentanil and fentanyl, across various types of anesthesia, as a function of American Society of Anesthesiologists physical status designations, and over a range of ages and body morphologies. CONCLUSION: Nociception level appears to provide accurate estimates of intraoperative nociception over a broad range of patients and anesthetic conditions.

Variation in the HA antigenicity of A(H1N1)pdm09-related swine influenza viruses.

Since the influenza pandemic in 2009, the causative agent 'A(H1N1)pdm09 virus', has been circulating in both human and swine populations. Although phylogenetic analyses of the haemagglutinin (HA) gene segment have revealed broader genetic diversity of A(H1N1)pdm09-related swine influenza A viruses (swIAVs) compared with human A(H1N1)pdm09 viruses, it remains unclear whether the genetic diversity reflects the antigenic differences in HA. To assess the impact of the diversity of the HA gene of A(H1N1)pdm09-related swIAVs on HA antigenicity, we characterized 12 swIAVs isolated in Japan from 2013 to 2018. We used a ferret antiserum and a panel of anti-HA mouse monoclonal antibodies (mAbs) raised against an early A(H1N1)pdm09 isolate. The neutralization assay with the ferret antiserum revealed that five of the 12 swIAVs were significantly different in their HA antigenicity from the early A(H1N1)pdm09 isolate. The mAbs also showed differential neutralization patterns depending on the swIAV strains. In addition, the single amino acid substitution at position 190 of HA, which was found in one of the five antigenically different swIAVs but not in human isolates, was shown to be one of the critical determinants for the antigenic difference of swIAV HAs. Two potential N-glycosylation sites at amino acid positions 185 and 276 of the HA molecule were identified in two antigenically different swIAVs. These results indicated that the genetic diversity of HA in the A(H1N1)pdm09-related swIAVs is associated with their HA antigenic variation. Our findings highlighted the need for surveillance to monitor the emergence of swIAV antigenic variants with public health importance.

Hardware-in-the-Loop Simulations with Umbra Conditions for Spacecraft Rendezvous with PMD Visual Sensors.

This paper addresses the validation of a robust vision-based pose estimation technique using a Photonic Mixer Device (PMD) sensor as a single visual sensor in the close-range phase of spacecraft rendezvous. First, it was necessary to integrate the developed hybrid navigation technique for the PMD sensor into the hardware-in-the-loop (HIL) rendezvous system developed by the German Aerospace Center (DLR). Thereafter, HIL tests were conducted using the European Proximity Operation Simulator (EPOS) with sun simulation and in total darkness. For the future missions with an active sensor, e.g., a PMD camera, it could be useful to use only its own illumination during the rendezvous phase in penumbra or umbra, instead of additional flash light. In some tests, the rotational rate of the target object was also tuned. Unlike the rendezvous tests in other works, here we present for the first time closed-loop approaches with only depth and amplitude images of a PMD sensor. For the rendezvous tests in the EPOS laboratory, the Argos3D camera was used at the range of 8 to 5.5 m; the performance showed promising results.

Placental mesenchymal dysplasia - morphology and differential diagnosis.

Placental mesenchymal dysplasia is a rare placental lesion characterized by placentomegaly, vascular abnormalities and formation of cystic structures in the placental parenchyma. It can be associated with various genetic abnormalities, fetal growth restriction or intrauterine fetal demise. Placental mesenchymal dysplasia needs to be distinguished from its main differential diagnosis, partial hydatidiform mole. The aim of this article is to provide readers with a basic overview of the morphology and differential diagnosis of this pathological entity.

Modeling the Mutational and Phenotypic Landscapes of Pelizaeus-Merzbacher Disease with Human iPSC-Derived Oligodendrocytes.

Pelizaeus-Merzbacher disease (PMD) is a pediatric disease of myelin in the central nervous system and manifests with a wide spectrum of clinical severities. Although PMD is a rare monogenic disease, hundreds of mutations in the X-linked myelin gene proteolipid protein 1 (PLP1) have been identified in humans. Attempts to identify a common pathogenic process underlying PMD have been complicated by an incomplete understanding of PLP1 dysfunction and limited access to primary human oligodendrocytes. To address this, we generated panels of human induced pluripotent stem cells (hiPSCs) and hiPSC-derived oligodendrocytes from 12 individuals with mutations spanning the genetic and clinical diversity of PMD-including point mutations and duplication, triplication, and deletion of PLP1-and developed an in vitro platform for molecular and cellular characterization of all 12 mutations simultaneously. We identified individual and shared defects in PLP1 mRNA expression and splicing, oligodendrocyte progenitor development, and oligodendrocyte morphology and capacity for myelination. These observations enabled classification of PMD subgroups by cell-intrinsic phenotypes and identified a subset of mutations for targeted testing of small-molecule modulators of the endoplasmic reticulum stress response, which improved both morphologic and myelination defects. Collectively, these data provide insights into the pathogeneses of a variety of PLP1 mutations and suggest that disparate etiologies of PMD could require specific treatment approaches for subsets of individuals. More broadly, this study demonstrates the versatility of a hiPSC-based panel spanning the mutational heterogeneity within a single disease and establishes a widely applicable platform for genotype-phenotype correlation and drug screening in any human myelin disorder.

An Improved Calibration Method for Photonic Mixer Device Solid-State Array Lidars Based on Electrical Analog Delay.

As a typical application of indirect-time-of-flight (ToF) technology, photonic mixer device (PMD) solid-state array Lidar has gained rapid development in recent years. With the advantages of high resolution, frame rate and accuracy, the equipment is widely used in target recognition, simultaneous localization and mapping (SLAM), industrial inspection, etc. The PMD Lidar is vulnerable to several factors such as ambient light, temperature and the target feature. To eliminate the impact of such factors, a proper calibration is needed. However, the conventional calibration methods need to change several distances in large areas, which result in low efficiency and low accuracy. To address the problems, this paper presents an improved calibration method based on electrical analog delay. The method firstly eliminates the lens distortion using a self-adaptive interpolation algorithm, meanwhile it calibrates the grayscale image using an integral time simulating based method. Then, the grayscale image is used to estimate the parameters of ambient light compensation in depth calibration. Finally, by combining four types of compensation, the method effectively improves the performance of depth calibration. Through several experiments, the proposed method is more adaptive to multiscenes with targets of different reflectivities, which significantly improves the ranging accuracy and adaptability of PMD Lidar.

Clinical and genetic aspects of hereditary spastic paraplegia in patients from Turkey.

OBJECTIVES: Hereditary spastic paraplegias (HSPs) are a heterogenous group of rare neurodegenerative disorders that present with lower limb spasticity. It is known as complicated HSP if spasticity is accompanied by additional features such as cognitive impairment, cerebellar syndrome, thin corpus callosum, or neuropathy. Most HSP families show autosomal dominant (AD) inheritance. On the other hand, autosomal recessive (AR) cases are also common because of the high frequency of consanguineous marriages in our country. This study aimed to investigate the clinical and genetic aetiology in a group of HSP patients. PATIENTS AND METHODS: We studied 21 patients from 17 families. Six of them presented with recessive inheritance. All index patients were screened for ATL1 and SPAST gene mutations to determine the prevalence of the most frequent types of HSP in our cohort. Whole exome sequencing was performed for an AD-HSP family, in combination with homozygosity mapping for five selected AR-HSP families. RESULTS: Two novel causative variants were identified in PLP1 and SPG11 genes, respectively. Distribution of HSP mutations in our AD patients was found to be similar to European populations. CONCLUSION: Our genetic studies confirmed that clinical analysis can be misleading when defining HSP subtypes. Genetic testing is an important tool for diagnosis and genetic counselling. However, in the majority of AR HSP cases, a genetic diagnosis is not possible.

Functional neuroimaging of recovery from motor conversion disorder: A case report.

A patient with motor conversion disorder presented with a functional paresis of the left hand. After exclusion of structural brain damage, she was repeatedly examined with whole-brain functional magnetic resonance imaging, while she performed visually paced finger-tapping tasks. The dorsal premotor cortex showed a bilateral deactivation in the acute-subacute phase. Recovery from unilateral hand paresis was associated with a gradual increase in task-based activation of the dorsal premotor cortex bilaterally. The right medial prefrontal cortex displayed the opposite pattern, showing initial task-based activation that gradually diminished with recovery. The inverse dynamics of premotor and medial prefrontal activity over time were found during unimanual finger-tapping with the affected and non-affected hand as well as during bimanual finger-tapping. These observations suggest that reduced premotor and increased medial prefrontal activity reflect an effector-independent cortical dysfunction in conversion paresis which gradually disappears in parallel with clinical remission of paresis. The results link the medial prefrontal and dorsal premotor areas to the generation of intentional actions. We hypothesise that an excessive 'veto' signal generated in medial prefrontal cortex along with decreased premotor activity might constitute the functional substrate of conversion disorder. This notion warrants further examination in a larger group of affected patients.

CMOS Image Sensors and Plasma Processes: How PMD Nitride Charging Acts on the Dark Current.

Plasma processes are known to be prone to inducing damage by charging effects. For CMOS image sensors, this can lead to dark current degradation both in value and uniformity. An in-depth analysis, motivated by the different degrading behavior of two different plasma processes, has been performed in order to determine the degradation mechanisms associated with one plasma process. It is based on in situ plasma-induced charge characterization techniques for various dielectric stack structures (dielectric nature and stack configuration). A degradation mechanism is proposed, highlighting the role of ultraviolet (UV) light from the plasma in creating an electron hole which induces positive charges in the nitride layer at the wafer center, and negative ones at the edge. The trapped charges de-passivate the SiO2/Si interface by inducing a depleted interface above the photodiode, thus emphasizing the generation of dark current. A good correlation between the spatial distribution of the total charges and the value of dark current has been observed.

Measurement of the Three-Dimensional Shape of Discontinuous Specular Objects Using Infrared Phase-Measuring Deflectometry.

Phase-measuring deflectometry (PMD)-based methods have been widely used in the measurement of the three-dimensional (3D) shape of specular objects, and the existing PMD methods utilize visible light. However, specular surfaces are sensitive to ambient light. As a result, the reconstructed 3D shape is affected by the external environment in actual measurements. To overcome this problem, an infrared PMD (IR-PMD) method is proposed to measure specular objects by directly establishing the relationship between absolute phase and depth data for the first time. Moreover, the proposed method can measure discontinuous surfaces. In addition, a new geometric calibration method is proposed by combining fringe projection and fringe reflection. The proposed IR-PMD method uses a projector to project IR sinusoidal fringe patterns onto a ground glass, which can be regarded as an IR digital screen. The IR fringe patterns are reflected by the measured specular surfaces, and the deformed fringe patterns are captured by an IR camera. A multiple-step phase-shifting algorithm and the optimum three-fringe number selection method are applied to the deformed fringe patterns to obtain wrapped and unwrapped phase data, respectively. Then, 3D shape data can be directly calculated by the unwrapped phase data on the screen located in two positions. The results here presented validate the effectiveness and accuracy of the proposed method. It can be used to measure specular components in the application fields of advanced manufacturing, automobile industry, and aerospace industry.

A Fast Calibration Method for Photonic Mixer Device Solid-State Array Lidars.

The photonic mixer device (PMD) solid-state array lidar, as a three-dimensional imaging technology, has attracted research attention in recent years because of its low cost, high frame rate, and high reliability. To address the disadvantages of traditional PMD solid-state array lidar calibration methods, including low calibration efficiency and accuracy, and serious human error factors, this paper first proposes a calibration method for an array complementary metal⁻oxide⁻semiconductor photodetector using a black-box calibration device and an electrical analog delay method; it then proposes a modular lens distortion correction method based on checkerboard calibration and pixel point adaptive interpolation optimization. Specifically, the ranging error source is analyzed based on the PMD solid-state array lidar imaging mechanism; the black-box calibration device is specifically designed for the calibration requirements of anti-ambient light and an echo reflection route; a dynamic distance simulation system integrating the laser emission unit, laser receiving unit, and delay control unit is designed to calibrate the photodetector echo demodulation; the checkerboard calibration method is used to correct external lens distortion in grayscale mode; and the pixel adaptive interpolation strategy is used to reduce distortion of distance images. Through analysis of the calibration process and results, the proposed method effectively reduces the calibration scene requirements and human factors, meets the needs of different users of the lens, and improves both calibration efficiency and measurement accuracy.

Is involvement of inflammation underestimated in Pelizaeus-Merzbacher disease?

Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating leukodystrophy resulting from proteolipid protein 1 gene (PLP1) mutations leading to oligodendrocyte loss. While neuroinflammation has recently become a common feature and actor in neurodegenerative diseases, the involvement of inflammation in PMD physiopathology is still highly debated despite evidence for strong astrogliosis and microglial cell activation. Activation of the innate immune system, and more particularly, of microglia and astrocytes, is mostly associated with the deleterious role of neuroinflammation. However, in diseases such as multiple sclerosis, microglia appear beneficial for repair based on their role in myelin debris removal or recruitment and differentiation of oligodendrocyte progenitor cells. In this review, we will discuss recent published data in terms of their relevance to the role of microglia in PMD evolution, and of their impact on the improvement of therapeutic approaches combining immunomodulation and cell therapy to promote optimal recovery. © 2016 Wiley Periodicals, Inc.

Fourth consensus of the International Society for Premenstrual Disorders (ISPMD): auditable standards for diagnosis and management of premenstrual disorder.

Whilst professional bodies such as the Royal College and the American College of Obstetricians and Gynecologists have well-established standards for audit of management for most gynaecology disorders, such standards for premenstrual disorders (PMDs) have yet to be developed. The International Society of Premenstrual Disorders (ISPMD) has already published three consensus papers on PMDs covering areas that include definition, classification/quantification, clinical trial design and management (American College Obstetricians and Gynecologists 2011; Brown et al. in Cochrane Database Syst Rev 2:CD001396, 2009; Dickerson et al. in Am Fam Physician 67(8):1743-1752, 2003). In this fourth consensus of ISPMD, we aim to create a set of auditable standards for the clinical management of PMDs. All members of the original ISPMD consensus group were invited to submit one or more auditable standards to be eligible in the inclusion of the consensus. Ninety-five percent of members (18/19) responded with at least one auditable standard. A total of 66 auditable standards were received, which were returned to all group members who then ranked the standards in order of priority, before the results were collated. Proposed standards related to the diagnosis of PMDs identified the importance of obtaining an accurate history, that a symptom diary should be kept for 2 months prior to diagnosis and that symptom reporting demonstrates symptoms in the premenstrual phase of the menstrual cycle and relieved by menstruation. Regarding treatment, the most important standards were the use of selective serotonin reuptake inhibitors (SSRIs) as a first line treatment, an evidence-based approach to treatment and that SSRI side effects are properly explained to patients. A set of comprehensive standards to be used in the diagnosis and treatment of PMD has been established, for which PMD management can be audited against for standardised and improved care.

Thermal injury to corticospinal tracts and postoperative motor deficits after laser interstitial thermal therapy.

OBJECTIVE Laser interstitial thermal therapy (LITT) has been increasingly used to treat deep-seated tumors. Despite its being minimally invasive, there is a risk of LITT damaging adjacent critical structures, including corticospinal tracts (CSTs). In this study, the authors investigated the predictive value of overlap between the hyperthermic field and CSTs in determining postoperative motor deficit (PMDs). METHODS More than 140 patients underwent an LITT procedure in our institution between April 2011 and June 2015. Because of the tumor's proximity to critical structures, 80 of them underwent preoperative diffusion tensor imaging and were included in this study. Extent of the hyperthermic field was delineated by the software as thermal-damage-threshold (TDT) lines (yellow [43°C for 2 minutes], blue [43°C for 10 minutes], and white [43°C for 60 minutes]). The maximum volume and the surface area of overlaps between motor fibers and the TDT lines were calculated and compared with the PMDs. RESULTS High-grade glioma (n = 46) was the most common indication for LITT. Postoperative motor deficits (partial or complete) were seen in 14 patients (11 with permanent and 3 with temporary PMDs). The median overlap volumes between CSTs with yellow, blue, and white TDT lines in patients with any PMD (temporary or permanent) were 1.15, 0.68, and 0.41 cm3, respectively. The overlap volumes and surface areas revealed significant differences in those with PMDs and those with no deficits (p = 0.0019 and 0.003, 0.012 and 0.0012, and 0.001 and 0.005 for the yellow, blue, and white TDT lines, respectively). The receiver operating characteristic was used to select the optimal cutoff point of the overlapped volumes and areas. Cutoff points for overlap volumes and areas based on optimal sensitivity (92%-100%) and specificity (80%-90%) were 0.103, 0.068, and 0.046 cm3 and 0.15, 0.07, and 0.11 mm2 for the yellow, blue, and white TDT lines, respectively. CONCLUSIONS Even a minimal overlap between the TDT lines and CSTs can cause a PMD after LITT. Precise planning and avoidance of critical structures and important white matter fibers should be considered when treating deep-seated tumors.

Determinants of parathyroid hormone response to vitamin D supplementation: a systematic review and meta-analysis of randomised controlled trials.

This systematic review aimed to assess the determinants of the parathyroid hormone (PTH) level response to vitamin D supplementation. We searched Medline, Google Scholar and the reference lists of previous reviews. All randomised controlled trials (RCT) on vitamin D supplementation that involved apparently healthy human subjects with a report of PTH were selected. Potential studies were screened independently and in duplicate. Results are summarised as mean differences with 95% confidence intervals. Quality assessment, subgroup analysis, meta-analysis and meta-regression analysis were carried out. Thirty-three vitamin D supplementation RCT were included. Vitamin D supplementation significantly raised circulating 25-hydroxyvitamin D (25(OH)D) with significant heterogeneity among studies with a pooled mean difference (PMD) of 15.5 ng/ml (test for heterogeneity: P<0·001 and I 2=97·3%). Vitamin D supplementation significantly reduced PTH level with PMD of -8·0 pg/ml, with significant heterogeneity ((test for heterogeneity: P<0·001) and the I 2 value was 97·3%). In the subgroup analyses, the optimum treatment effect for PTH was observed with Ca doses of 600-1200 mg/d (-22·48 pg/ml), after the duration of a >12-month trial (-18·36 pg/ml), with low baseline 25(OH)D concentration of <20 ng/ml (-16·70 pg/ml) and in those who were overweight and obese (-18·11 pg/ml). Despite the present meta-analysis being hindered by some limitations, it provided some interesting evidence, suggesting that suppression of PTH level needs higher vitamin D intake (75 µg/d) than the current recommendations and longer durations (12 months), which should be taken into account for nutritional recommendations.

Riding Toward Danger: A Scoping Review of Burns Associated With Personal Mobility Devices, Including Electric Bikes (E-Bikes) and Electric Scooters (E-Scooters).

Burn injuries related to lithium-ion batteries from personal mobility devices, such as electric bikes and electric scooters, have emerged as a global concern. By examining the literature, this study aims to provide an overview of the demographics, patterns, and outcomes of personal mobility device-associated burns. A Singaporean cohort revealed burns resulting predominantly from fires occurring due to the combustion of unattended personal mobility device batteries during charging. In contrast, an Israeli cohort showed a higher total body surface area and highlighted the vulnerability of limbs to burn injuries in such incidents. A Beijing cohort, consisting of pediatric patients indicated potential child safety concerns regarding personal mobility device usage. Finally, a Shanghai cohort demonstrated the potential dangers of personal mobility device battery chargers. The observed differences between those experiencing burn injuries and the broader population of personal mobility device riders in terms of age and gender suggest that younger males may be at higher risk, perhaps due to risky practices such as leaving personal mobility devices unattended while charging. This review emphasizes the need for safety education, adherence to regulations, and responsible consumer choices to mitigate burn injuries. Recommendations include promoting child safety measures, using certified personal mobility devices, and cautious handling of DIY conversion kits. Further large-scale studies are essential to gain comprehensive insights and develop effective safety strategies to protect personal mobility device riders from burn injuries.

Genome-wide association study and haplotype analysis reveal novel candidate genes for resistance to powdery mildew in soybean.

Powdery mildew disease (PMD) is caused by the obligate biotrophic fungus Microsphaera diffusa Cooke & Peck (M. diffusa) and results in significant yield losses in soybean (Glycine max (L.) Merr.) crops. By identifying disease-resistant genes and breeding soybean accessions with enhanced resistance, we can effectively mitigate the detrimental impact of PMD on soybeans. We analyzed PMD resistance in a diversity panel of 315 soybean accessions in two locations over 3 years, and candidate genes associated with PMD resistance were identified through genome-wide association studies (GWAS), haplotype analysis, qRT-PCR, and EMS mutant analysis. Based on the GWAS approach, we identified a region on chromosome 16 (Chr16) in which 21 genes form a gene cluster that is highly correlated with PMD resistance. In order to validate and refine these findings, we conducted haplotype analysis of 21 candidate genes and indicated there are single nucleotide polymorphisms (SNPs) and insertion-deletions (InDels) variations of Glyma.16G214000, Glyma.16G214200, Glyma.16G215100 and Glyma.16G215300 within the coding and promoter regions that exhibit a strong association with resistance against PMD. Subsequent structural analysis of candidate genes within this cluster revealed that in 315 accessions, the majority of accessions exhibited resistance to PMD when Glyma.16G214300, Glyma.16G214800 and Glyma.16G215000 were complete; however, they demonstrated susceptibility to PMD when these genes were incomplete. Quantitative real-time PCR assays (qRT-PCR) of possible candidate genes showed that 14 candidate genes (Glyma.16G213700, Glyma.16G213800, Glyma.16G213900, Glyma.16G214000, Glyma.16G214200, Glyma.16G214300, Glyma.16G214500, Glyma.16G214585, Glyma.16G214669, Glyma.16G214700, Glyma.16G214800, Glyma.16G215000, Glyma.16G215100 and Glyma.16G215300) were involved in PMD resistance. Finally, we evaluated the PMD resistance of mutant lines from the Williams 82 EMS mutations library, which revealed that mutants of Glyma.16G214000, Glyma.16G214200, Glyma.16G214300, Glyma.16G214800, Glyma.16G215000, Glyma.16G215100 and Glyma.16G215300, exhibited sensitivity to PMD. Combined with the analysis results of GWAS, haplotypes, qRT-PCR and mutants, the genes Glyma.16G214000, Glyma.16G214200, Glyma.16G214300, Glyma.16G214800, Glyma.16G215000, Glyma.16G215100 and Glyma.16G215300 were identified as highly correlated with PMD resistance. The candidate genes identified above are all NLR family genes, and these discoveries deepen our understanding of the molecular basis of PMD resistance in soybeans and will be useful for guiding breeding strategies.

Application of a Revised Tissue Saving Protocol for Combined Topography-Guided Photorefractive Keratectomy and Cross-Linking in a Cohort Having Pellucid Marginal Degeneration.

Purpose: To evaluate the efficiency, safety, and stability of a revised tissue-saving treatment protocol in a cohort having pellucid marginal degeneration (PMD). Methods: A retrospective cohort study was conducted on patients with PMD and no previous treatments. A revised protocol of topo-guided photorefractive keratectomy to be followed by customized phototherapeutic keratectomy and then corneal crosslinking was evaluated by comparing the pre and postoperative outcomes regarding visual (subjective refraction) and topographic (using data from Sirius CSO topography software) outcomes. Results: There were both statistically significant and clinically relevant improvements in the postoperative parameters, where each of the unaided and corrected visual acuity, spherical equivalent, refractive cylinder, K readings, topographic cylinder, inferior minus superior difference at the 2- and 4- mm diameters, coma aberration, and higher order aberrations were significantly better postoperatively (all p values were less than 0.01, except for maximum k readings where the p-value was 0.017). The safety and efficacy indices for the surgical procedure were remarkably high (1.53 ± 0.70 and 0.90 ± 0.32, respectively). Conclusion: Our proposed tissue-saving protocol (which showed satisfactory results in keratoconus cases according to a previously published article by our research team) has proven its successful outcomes (both topographically and visually) in cases of PMD, which is a rare ectatic entity with guarded prognosis using the available conventional ectasia treatment modalities.

Evaluation and analysis of influencing factors of placental mesenchymal dysplasia diagnosed using prenatal ultrasonography and pregnancy outcomes: case series.

Background: Placental mesenchymal dysplasia (PMD) is a rare placental vascular malformation of unknown etiology. PMD may coexist with a healthy fetus, and its ultrasound appearance is similar to that of a hydatidiform mole, especially the partial type. Prenatal ultrasonography is vital for accurate diagnosis of these conditions. This study aimed to summarize the characteristics of prenatal ultrasonographic images across different gestational weeks (W) for PMD and evaluate and analyze factors that influence pregnancy outcomes related to PMD. The goal is to improve the diagnosis of PMD, effectively assess fetal prognosis, and provide a reference for prenatal consultations and clinical management. Case Description: Of the 15 included patients, 4, 8, and 3 had PMD in early pregnancy (<13+6 W), mid-pregnancy (approximately 14-27+6 W), and late pregnancy (>28 W), respectively. Among the 15 patients, 5 successfully underwent delivery, thereby resulting in fetal survival; 3 experienced intrauterine death, 1 had a miscarriage, and 6 pregnancies were terminated. During early pregnancy, ultrasonographic manifestations of PMD included microscopic anechoic cystic areas in the placental parenchyma. In the second trimester, the placenta exhibited diffuse enlargement and thickening, with the placental parenchyma showing cellular anechoic cystic areas clearly separated from the surrounding normal placental tissue. As the pregnancy progressed, the cystic areas gradually reduced in the third trimester. Additionally, localized umbilical blood vessels showed tumorous lesions, sometimes accompanied by intravascular thrombosis. Some cases exhibited tortuosity and dilation in the umbilical vein. Conclusions: PMD exhibited varying ultrasonographic characteristics across different gestational stages and demonstrated regular disease evolution corresponding to gestational W. This condition is associated with adverse pregnancy outcomes, with the location, extent, and severity of lesions being crucial factors affecting fetal development in utero.