Impact of pulsed electric field intensity on the cream separation efficiency from bovine milk and physico-chemical properties of the cream.

Low-temperature (9-12 °C) pulsed electric field (PEF) was investigated in milk before cream separation at different intensities (9-27 kV/cm, 66 µs, 16-28 kJ/L) regarding its potential to render processing more sustainable, retain a high physico-chemical quality, enhance functional properties, and gently modify the structure of the milk fat globule membrane (MFGM). Cream volume per L milk were most efficiently increased by 31 % at the lowest PEF intensity in comparison to untreated milk and cream (P < 0.05). Untreated and PEF-treated milk and obtained cream were assessed with compositional (fat, protein, casein, lactose, and total solids content) and particle size distribution analyses, showing no significant differences (P ≥ 0.05) and, thus, indicating retention of 'native-like' product quality. Overrun and stability of cream, whipped for 20 and 60 s at 15000 rpm using a high-shear mixer, were improved most notably by the lowest and the highest PEF intensities, achieving up to 69 % enlarged overrun and up to 22 % higher stability, respectively (P < 0.05), than in untreated whipped cream. Protein component analyses for milk and cream were carried out by sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Noticeable differences between untreated and PEF-treated milk were not observed, but the SDS-PAGE results for cream showed noticeably different bands for some of the protein components, indicating structural changes in MFGM-, whey-, and phospho-proteins due to PEF and/or separator processing effects. More intense bands of xanthine oxidase, xanthine dehydrogenase, butyrophilin, bovine serum albumine, adipophilin (ADPH), and glycoproteins PAS6/7 were observed specifically at 21 kV/cm. Gentle electroporation of both MFGM layers by PEF was determined based on the changes in MFGM monolayer components, such as ADPH and PAS 6/7, exhibiting intensified bands. PEF intensity-dependent impact on the structure of MFGM and casein, leading to a reconfiguration of the cream matrix due to different structuring interactions among proteins, among milk fat globules, and between fat and protein components, was suggested. Overall, low-temperature PEF applied at different intensities showed great potential for gentle, efficient, and functional properties-tailored dairy processing and may also enable effective extraction of highly bioactive ingredients from dairy sources.

Posterior Communicating Artery Aneurysm With Referred Tooth Pain: A Case Report.

Oculomotor nerve (CN III) palsy (ONP) has multiple etiologies, with aneurysms and ischemic injury being the two leading causes. The presentations of these conditions differ, as aneurysms commonly manifest with pupillary involvement, while ischemic-related ONP often leads to a pupil-sparing presentation. We present a 63-year-old African American male with a history of sickle cell trait, ocular sickle cell disease, and untreated hypertension that develops "down and out" left eye with a mid-dilated pupil unresponsive to light. However, the patient developed severe left upper tooth pain after the onset of the eye pain, which progressed to ONP. The patient's dental and radiographic evaluation did not indicate any obvious source for his tooth pain. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the head revealed a 7-mm saccular aneurysm with a 2-mm neck arising from the left posterior communicating artery (PCOM) aneurysm, and neurovascular surgical intervention was initiated. This case highlights the potential of referred tooth pain as an early symptom in patients with PCOM aneurysm, which physicians should be vigilant about and consider as a potential indicator of the condition. Therefore, collaboration between different specialties, including ophthalmology, neurology, neurosurgery, and dental care, is necessary to formulate a comprehensive treatment plan that effectively addresses the patient's specific needs and challenges.

Comparative Analysis of Machine Learning Models for Image Detection of Colonic Polyps vs. Resected Polyps.

(1) Background: Colon polyps are common protrusions in the colon's lumen, with potential risks of developing colorectal cancer. Early detection and intervention of these polyps are vital for reducing colorectal cancer incidence and mortality rates. This research aims to evaluate and compare the performance of three machine learning image classification models' performance in detecting and classifying colon polyps. (2) Methods: The performance of three machine learning image classification models, Google Teachable Machine (GTM), Roboflow3 (RF3), and You Only Look Once version 8 (YOLOv8n), in the detection and classification of colon polyps was evaluated using the testing split for each model. The external validity of the test was analyzed using 90 images that were not used to test, train, or validate the model. The study used a dataset of colonoscopy images of normal colon, polyps, and resected polyps. The study assessed the models' ability to correctly classify the images into their respective classes using precision, recall, and F1 score generated from confusion matrix analysis and performance graphs. (3) Results: All three models successfully distinguished between normal colon, polyps, and resected polyps in colonoscopy images. GTM achieved the highest accuracies: 0.99, with consistent precision, recall, and F1 scores of 1.00 for the 'normal' class, 0.97-1.00 for 'polyps', and 0.97-1.00 for 'resected polyps'. While GTM exclusively classified images into these three categories, both YOLOv8n and RF3 were able to detect and specify the location of normal colonic tissue, polyps, and resected polyps, with YOLOv8n and RF3 achieving overall accuracies of 0.84 and 0.87, respectively. (4) Conclusions: Machine learning, particularly models like GTM, shows promising results in ensuring comprehensive detection of polyps during colonoscopies.

Cat Eye Syndrome with a Unique Liver and Dermatological Presentation.

Cat eye syndrome (CES), also known as Schmid-Fraccaro syndrome, is a complex genetic syndrome with a highly variable phenotype that includes ocular coloboma, anal atresia, preauricular skin tags and pits, heart defects, kidney malformations, dysmorphic facial features, and mild to moderate intellectual disability. We describe a case of a 23-year-old male with a past medical history of CES with short stature, mild learning disability, and some dysmorphic facial features who presented with recurrent pruritus and rashes and had mild liver dysfunction. Furthermore, the patient did not have the classic presentation of CES but a clinically milder expression of the phenotypes. Abnormalities in the abdominal ultrasound prompted an ultrasound-guided liver biopsy, which showed bile ductular proliferation with mild portal inflammation composed of lymphocytes and plasma cells, and bridging fibrosis. The patient's labs showed elevated immunoglobulins with the highest increase observed in IgG, along with negative antinuclear antibodies (ANA), negative anti-mitochondrial antibody, and negative hepatitis A/B/C but a weak positive anti-smooth muscle antibody (ASMA). These findings indicated that the patient most likely had autoimmune hepatitis (AIH) or an overlap syndrome with primary sclerosing cholangitis (PSC). The patient was initially treated with steroids and antihistamines for pruritus, which led to some clinical improvement. After dermatological evaluation, the patient was diagnosed with atopic dermatitis and was recently started on a dupilumab 600 mg loading dose and would continue with biweekly dupilumab 300 mg injections. This dermatological finding may require additional examination and can be a unique presentation in patients with CES. This case illustrates that even patients with milder CES expression can experience intense dermatological complications if not effectively managed. CES is a multifactorial disease that requires intervention from multiple specialists. Therefore, primary care physicians must be aware of the potential complications of CES and make adequate referrals to closely monitor patients' symptoms.

Inverse Saxophone-A Device to Study the Role of Individual Finger Perturbations on Grasp Stability.

The efficient coordination of fingertip forces to maintain static equilibrium while grasping an object continues to intrigue scientists. While many studies have explored this coordination, most of these studies assumed that interactions of hands primarily occur with rigid inanimate objects. Instead, our daily interactions with living and nonliving entities involve many dynamic, compliant, or fragile bodies. This paper investigates the fingertip force coordination on a manipulandum that changes its shape while grasping it. We designed a five-finger perturbation system with linear actuators at positions corresponding to each finger that would protrude outward from the center of the handle or retract toward the center of the handle as programmed. The behavior of the perturbed fingers and the other fingers while grasping this device was studied. Based on previous experiments on expanding and contracting handles, we hypothesized that each finger would exhibit a comparable response to similar horizontal perturbations. However, the response of the little finger was significantly different from the other fingers. We speculate that the central nervous system demonstrates preferential recruitment of some fingers over others while performing a task.

Developing frailty friendly hospitals: the Specialised Clinical Frailty Network.

Introduction: The aim of the Specialised Clinical Frailty Network (SCFN) was to develop frailty-attuned pathways in specialised services in England. Methods: We developed a breakthrough series collaborative involving a range of specialised services, using quality improvement methods (including experience-based design) to implement improvements designed to enhance the experience and outcomes of older people living with frailty who have specialised healthcare needs. Results: Specialised teams responded positively to the SCFN, many implementing process changes aligned to the needs of older people living with frailty. Some were able to demonstrate improvements in service and/or patient outcomes, including greater identification of frailty, more holistic care and increased use of shared decision making. Discussion: The network has successfully demonstrated how frailty can be assessed both at individual, as well as population level, to support both local teams and systems to best manage the health of their patients.

Virtual reality validation of naturalistic modulation strategies to counteract fading in retinal stimulation.

Objective. Temporal resolution is a key challenge in artificial vision. Several prosthetic approaches are limited by the perceptual fading of evoked phosphenes upon repeated stimulation from the same electrode. Therefore, implanted patients are forced to perform active scanning, via head movements, to refresh the visual field viewed by the camera. However, active scanning is a draining task, and it is crucial to find compensatory strategies to reduce it.Approach. To address this question, we implemented perceptual fading in simulated prosthetic vision using virtual reality. Then, we quantified the effect of fading on two indicators: the time to complete a reading task and the head rotation during the task. We also tested if stimulation strategies previously proposed to increase the persistence of responses in retinal ganglion cells to electrical stimulation could improve these indicators.Main results. This study shows that stimulation strategies based on interrupted pulse trains and randomisation of the pulse duration allows significant reduction of both the time to complete the task and the head rotation during the task.Significance. The stimulation strategy used in retinal implants is crucial to counteract perceptual fading and to reduce active head scanning during prosthetic vision. In turn, less active scanning might improve the patient's comfort in artificial vision.

Rhythmic gymnasts' injuries in a pediatric sports medicine clinic in the United States: a 10-year retrospective chart review.

OBJECTIVES: Rhythmic gymnastics injuries have not been studied thoroughly especially in the United States. Existing research studies are predominantly from Europe or Canada or from more than 15 years ago. The purpose of our study was to provide an updated description of injury patterns among rhythmic gymnasts in the United States. METHODS: A retrospective chart review was conducted of 193 rhythmic gymnastics injuries in 79 females, ages 6-20. Patients were seen between January 2010 and March 2020 in a hospital-based pediatric sports medicine clinic. Gymnast demographics, injury locations, and injury types were collected as available. Descriptive and bivariate statistical analysis was performed using general linear mixed models. RESULTS: Our cohort had a mean age of 14.61 ± 2.61 years. Overuse injuries (76.7%) were more common than acute injuries (23.3%). The most common injury types were strain (20.7%), nonspecific pain (15.5%), and tendinitis/tenosynovitis (10.36%). The most frequently injured body regions were lower extremity (75.1%), followed by trunk/back (19.2%), upper extremity (4.7%), and head/neck (1.0%). The most common injured body parts were foot (24.9%), ankle (15.5%), knee (15.0%), lower back (14.0%), and hip (13.0%). General linear mixed models revealed that older age (p = 0.001) and higher competitive level (p = 0.016) were associated with a greater number of diagnoses. Gymnasts with foot injuries were older than gymnasts with ankle (p = 0.026), hip (p < 0.0001), and knee (p = 0.002) injuries. Gymnasts with higher BMI-for-age percentile were more likely to have acute injuries than overuse (p = 0.035). CONCLUSION: Our data showed that injuries among rhythmic gymnasts were most frequently located in the lower extremities, specifically the foot, followed by trunk/back. Additionally, the most frequent injury types were strains and nonspecific pain, and overuse was the most prevalent mechanism. Gymnasts with foot injuries were older than gymnasts with ankle, hip, and knee injuries. Higher BMI is a predictor of acute injuries.

Virtual reality simulation of epiretinal stimulation highlights the relevance of the visual angle in prosthetic vision.

OBJECTIVE: Retinal prostheses hold the potential for artificial vision in blind patients suffering from outer retinal dystrophies. The optimal number, density and coverage of the electrodes that a retinal prosthesis should have to provide adequate artificial vision in daily activities is still an open question and an important design parameter needed to develop better implants. APPROACH: To address this question, we investigated the interaction between the visual angle, the pixel number and the pixel density without being limited by a small electrode count. We implemented prosthetic vision in a virtual reality environment in order to simulate the real-life experience of using a retinal prosthesis. We designed four different tasks simulating: object recognition, word reading, perception of a descending step and crossing a street. MAIN RESULTS: The results of our study showed that in all the tasks the visual angle played the most significant role in improving the performance of the participant. SIGNIFICANCE: The design of new retinal prostheses should take into account the relevance of the restored visual angle to provide a helpful and valuable visual aid to profoundly or totally blind patients.

The first complete genomic sequence of cardamom mosaic virus, a member of the genus Macluravirus (family Potyviridae).

The complete genome sequence of the KS isolate of cardamom mosaic virus (CdMV) was determined using transcriptome sequencing data from CdMV-infected Elettaria cardamomum as well as from overlapping cDNA clones made from RNA extracted from viral particles. The viral genome consists of 8249 nucleotides (nt) and encodes a large polyprotein of 2636 amino acids (aa). The polyprotein of CdMV shared 48.9%-67.4% aa sequence identity with other reported macluraviruses. Similar to the other members of genus Macluravirus, the genome of CdMV lacks the P1 coding region and the N-terminus of the HC-Pro coding region. The putative small open reading frame, PIPO, embedded within the P3 cistron, is preceded by a C(A)6 motif instead of G(A)6. Phylogenetic analysis based on the complete genome sequence aided the grouping of CdMV along with all other macluraviruses and showed that it is closely related to alpinia oxyphylla mosaic virus (AloMV). Among CdMV isolates, the KS isolate is most similar to the Appangala isolate based on disease symptoms and phylogeny.

Pollen morphology of certain species of the family Lamiaceae in Saudi Arabia.

The intention of the present wok is to provide an account on the pollen morphological features of Lamiaceae in Saudi Arabia as a basis for future studies of Lamiaceae pollens in the region. Pollen morphology of 20 species belong to 16 genera of the Lamiaceae has been investigated using Light Microscope (LM) and Scanning Electron Microscope (SEM). The study revealed that the pollen grains were characterized by 3-zonocolpate or 6-zonocolpate. Size of the pollen is variable between the genera but not among the species of the same genus. The surface pattern of the exine varies from fine reticulate, rough reticulate, mega-reticulate, reticulate-perforate, bireticulate-perforate or granulate, leading to 6 types of pollen grains. These variations revealed by this study implies that pollen Morphology may be of significant value sharing in solving problems in the classification of Lamiaceae members. A Key to the species, based on the morphological features of pollen grains, is also provided.

Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques.

Hepatitis B virus (HBV) is a major global health concern, and the development of curative therapeutics is urgently needed. Such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of HBV infection. Here, we report that expression of the HBV entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), on macaque primary hepatocytes facilitates HBV infection in vitro, where all replicative intermediates including covalently closed circular DNA (cccDNA) are present. Furthermore, viral vector-mediated expression of hNTCP on hepatocytes in vivo renders rhesus macaques permissive to HBV infection. These in vivo macaque HBV infections are characterized by longitudinal HBV DNA in serum, and detection of HBV DNA, RNA, and HBV core antigen (HBcAg) in hepatocytes. Together, these results show that expressing hNTCP on macaque hepatocytes renders them susceptible to HBV infection, thereby establishing a physiologically relevant model of HBV infection to study immune clearance and test therapeutic and curative approaches.

Extracorporeal Membrane Oxygenation for Hemophagocytic Lymphohistiocytosis.

BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) is a rare hematological disease characterized by an excessive inflammatory response to various triggers, resulting in rapid multi-organ failure. Its incidence may be underestimated due to its rarity, its variable clinical presentation, and its high mortality rate prior to diagnosis. Oftentimes, HLH is mistaken for refractory sepsis and improperly treated as such. Left untreated, the disease is universally fatal. With treatment, case series of adults with HLH report a 30-day mortality of up to 44% and an overall mortality of up to 75%. CASE REPORT We describe the use of extracorporeal membrane oxygenation (ECMO) in a previously healthy young man with HLH and acute respiratory distress syndrome (ARDS), a common sequela of HLH. ECMO was employed to provide temporary hemodynamic support, allowing for recovery of pulmonary function compromised during the initial cytokine storm. Additionally, and perhaps more importantly, implementation of ECMO provided the time necessary for the eventual diagnosis and treatment of HLH. CONCLUSIONS Although limited case reports and case series suggest that the use of ECMO in pediatric patients with HLH is associated with high mortality, our experience suggests that ECMO should not be rejected as a supportive modality in adults with HLH who have potentially recoverable cardiopulmonary function. We believe that ECMO may be appropriately instituted in select patients with HLH, or in rapidly deteriorating patients with an unknown illness refractory to conventional therapy, to allow for end-organ recovery, to reach a diagnosis, and to administer appropriate therapy.

Multiplexed imaging reveals heterogeneity of PI3K/MAPK network signaling in breast lesions of known PIK3CA genotype.

PURPOSE: Activating genetic changes in the phosphatidylinositol-3-kinase (PI3K) signaling pathway are found in over half of invasive breast cancers (IBCs). Previously, we discovered numerous hotspot PIK3CA mutations in proliferative breast lesions. Here, we investigate the spatial nature of PI3K pathway signaling and its relationship with PI3K genotype in breast lesions. METHODS: We identified PI3K phosphosignaling network signatures in columnar cell change (CCL), usual ductal hyperplasia (UDH), ductal carcinoma in situ (DCIS), and IBC in 26 lesions of known PIK3CA genotype from 10 human breast specimens using a hyperspectral-based multiplexed tissue imaging platform (MTIP) to simultaneously quantitate PI3K/MAPK pathway targets (pAKT473, pAKT308, pPRAS40, pS6, and pERK) in FFPE tissue, with single-cell resolution. RESULTS: We found that breast lesional epithelia contained spatially heterogeneous patterns of PI3K pathway phosphoprotein signatures, even within microscopic areas of CCL, UDH, DCIS, and IBC. Most lesions contained 3-12 unique phosphoprotein signatures within the same microscopic field. The dominant phosphoprotein signature for each lesion was not well correlated with lesion genotype or lesion histology, yet samples from the same patient tended to group together. Further, 5 UDH/CCL lesions across different patients had a common phosphosignature at the epithelial-stromal interface (possible myoepithelial cells) that was distinct from both the adjacent lesional epithelium and distinct from adjacent stroma. CONCLUSION: We present the first spatial mapping of PI3K phosphoprotein networks in proliferative breast lesions and demonstrate complex PI3K signaling heterogeneity that defies simple correlation between PIK3CA genotype and phosphosignal pattern.

Ultrasensitive proteomic quantitation of cellular signaling by digitized nanoparticle-protein counting.

Many important signaling and regulatory proteins are expressed at low abundance and are difficult to measure in single cells. We report a molecular imaging approach to quantitate protein levels by digitized, discrete counting of nanoparticle-tagged proteins. Digitized protein counting provides ultrasensitive molecular detection of proteins in single cells that surpasses conventional methods of quantitating total diffuse fluorescence, and offers a substantial improvement in protein quantitation. We implement this digitized proteomic approach in an integrated imaging platform, the single cell-quantum dot platform (SC-QDP), to execute sensitive single cell phosphoquantitation in response to multiple drug treatment conditions and using limited primary patient material. The SC-QDP: 1) identified pAKT and pERK phospho-heterogeneity and insensitivity in individual leukemia cells treated with a multi-drug panel of FDA-approved kinase inhibitors, and 2) revealed subpopulations of drug-insensitive CD34+ stem cells with high pCRKL and pSTAT5 signaling in chronic myeloid leukemia patient blood samples. This ultrasensitive digitized protein detection approach is valuable for uncovering subtle but important differences in signaling, drug insensitivity, and other key cellular processes amongst single cells.

Heterogeneous intracellular trafficking dynamics of brain-derived neurotrophic factor complexes in the neuronal soma revealed by single quantum dot tracking.

Accumulating evidence underscores the importance of ligand-receptor dynamics in shaping cellular signaling. In the nervous system, growth factor-activated Trk receptor trafficking serves to convey biochemical signaling that underlies fundamental neural functions. Focus has been placed on axonal trafficking but little is known about growth factor-activated Trk dynamics in the neuronal soma, particularly at the molecular scale, due in large part to technical hurdles in observing individual growth factor-Trk complexes for long periods of time inside live cells. Quantum dots (QDs) are intensely fluorescent nanoparticles that have been used to study the dynamics of ligand-receptor complexes at the plasma membrane but the value of QDs for investigating ligand-receptor intracellular dynamics has not been well exploited. The current study establishes that QD conjugated brain-derived neurotrophic factor (QD-BDNF) binds to TrkB receptors with high specificity, activates TrkB downstream signaling, and allows single QD tracking capability for long recording durations deep within the soma of live neurons. QD-BDNF complexes undergo internalization, recycling, and intracellular trafficking in the neuronal soma. These trafficking events exhibit little time-synchrony and diverse heterogeneity in underlying dynamics that include phases of sustained rapid motor transport without pause as well as immobility of surprisingly long-lasting duration (several minutes). Moreover, the trajectories formed by dynamic individual BDNF complexes show no apparent end destination; BDNF complexes can be found meandering over long distances of several microns throughout the expanse of the neuronal soma in a circuitous fashion. The complex, heterogeneous nature of neuronal soma trafficking dynamics contrasts the reported linear nature of axonal transport data and calls for models that surpass our generally limited notions of nuclear-directed transport in the soma. QD-ligand probes are poised to provide understanding of how the molecular mechanisms underlying intracellular ligand-receptor trafficking shape cell signaling under conditions of both healthy and dysfunctional neurological disease models.

Recent contributions of glaciers and ice caps to sea level rise.

Glaciers and ice caps (GICs) are important contributors to present-day global mean sea level rise. Most previous global mass balance estimates for GICs rely on extrapolation of sparse mass balance measurements representing only a small fraction of the GIC area, leaving their overall contribution to sea level rise unclear. Here we show that GICs, excluding the Greenland and Antarctic peripheral GICs, lost mass at a rate of 148 ± 30 Gt yr(-1) from January 2003 to December 2010, contributing 0.41 ± 0.08 mm yr(-1) to sea level rise. Our results are based on a global, simultaneous inversion of monthly GRACE-derived satellite gravity fields, from which we calculate the mass change over all ice-covered regions greater in area than 100 km(2). The GIC rate for 2003-2010 is about 30 per cent smaller than the previous mass balance estimate that most closely matches our study period. The high mountains of Asia, in particular, show a mass loss of only 4 ± 20 Gt yr(-1) for 2003-2010, compared with 47-55 Gt yr(-1) in previously published estimates. For completeness, we also estimate that the Greenland and Antarctic ice sheets, including their peripheral GICs, contributed 1.06 ± 0.19 mm yr(-1) to sea level rise over the same time period. The total contribution to sea level rise from all ice-covered regions is thus 1.48 ± 0.26 mm (-1), which agrees well with independent estimates of sea level rise originating from land ice loss and other terrestrial sources.

Treatment of pulmonary hypertension in patients with connective tissue disease and interstitial lung disease.

BACKGROUND: Pulmonary hypertension (PH) in patients with connective tissue disease (CTD) can occur in isolation or concomitantly with interstitial lung disease (ILD). Targeted therapies for PH can mitigate clinical deterioration in CTD patients with isolated PH; however, the effect of these therapies in CTD patients with PH and ILD (CTD-PH-ILD) are poorly characterized. OBJECTIVE: To investigate outcomes following long-term treatment of PH in patients with CTD-PH-ILD.  METHODS:   A retrospective evaluation of 13 CTD-PH-ILD patients who were treated with bosentan, sildenafil or bosentan plus sildenafil, was conducted. Immunosuppressants were prescribed as indicated. Patients underwent pulmonary function testing and assessment of 6 min walk distance at the time of treatment initiation and during follow-up. Patients were followed until time of death, lung transplantation or the end of the study. Kaplan-Meier estimates of survival were calculated and log-rank testing was used to analyze survival differences according to CTD subtype. RESULTS: Thirteen patients (seven with systemic sclerosis [SSc], four with overlap syndrome, and two with rheumatoid arthritis) were followed for a mean (± SD) duration of 33.8±21.7 months. The survival estimate at a median duration of 34 months was 85%; two patients with SSc died. Mortality rates were greater among patients with SSc versus other CTD subtypes (P=0.04). No changes from baseline to follow-up in mean forced vital capacity or exercise capacity, and no treatment-related toxicity, were observed. CONCLUSION: Treatment using PH-specific therapies in patients with CTD, PH and ILD was well tolerated. Further studies to investigate the efficacy of PH-specific therapies in CTD-PH-ILD patients are warranted.

Comprehensive maternal serum proteomic profiles of preclinical and clinical preeclampsia.

We systematically characterized maternal serum proteome in women with clinical preeclampsia (PE) and asymptomatic women in early pregnancy that subsequently developed PE. Clinical PE cohort comprised 30 patients with mild PE, 30 with severe PE, and 58 normotensive women. Preclinical PE cohort included 149 women whose serum samples were collected at 8-14 gestational weeks and in whom 30 women later developed mild and 40 severe PE. Serum proteome was analyzed and enzyme-linked immunosorbent assays were used for protein quantification. In Clinical PE, fibronectin, pappalysin-2, choriogonadotropin-beta, apolipoprotein C-III, cystatin-C, vascular endothelial growth factor receptor-1, and endoglin were more abundant compared to normotensive women. In preclinical PE, differently expressed proteins included placental, vascular, transport, matrix, and acute phase proteins. Angiogenic and antiangiogenic proteins were not significant. We conclude that placental and antiangiogenic proteins are abundant in clinical PE. In preclinical PE, proteomic profile is distinct and different from that in clinical PE.