Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteomics: A Novel Methodology to Complement Prenatal Diagnosis of Chromosomal Abnormalities and Inherited Human Diseases

The current revolution in biomedical sciences has raised new hope for early diagnosis, prevention, and treatment of human diseases. Recent advancements in genomics, proteomics, and other basic sciences are currently transforming the medical science, and offer the promise of answering many of the questions related to human diseases, including their early and accurate diagnosis. Proﬁling of biological ﬂuids (i.e., serum, urine, amniotic ﬂuid, and cerebrospinal ﬂuid) has successfully identiﬁed relevant protein biomarkers that potentially can change early diagnosis and treatment of several medical conditions related to human pregnancy. Similarly, proteomics holds the promise to complement genomics to revolutionize screening and prenatal diagnosis of genetic conditions during early pregnancy. This article summarizes current technology and reviews the application of proteomics in diagnosis of genetic disorders during human pregnancy.
ANEMIA DURING PREGNANCY AND BIRTH OUTCOME: A META-ANALYSIS

To determine the relationship between maternal anemia [hemoglobin (Hgb) < 10–11 g/dL] and various birth outcomes, a meta-analysis was conducted based on published literature identified by MEDLINE and manual search from 1966 through 1999. Odds ratios (OR) from selected studies were pooled according to the gestational age at anemia diagnosis. The meta-analysis shows that maternal anemia during early pregnancy was associated with slightly increased preterm birth [pooled adjusted OR (aOR): 1.32, 95% confidence interval (CI): 1.01–1.74], and nonstatistically significant increased low birth weight [pooled aOR: 1.39 (0.70–2.74)], and was not associated with fetal growth restriction [pooled aOR: 1.01 (0.73–1.38)]. However, there was a nonstatistically significant inverse relationship between anemia during late pregnancy and preterm birth [pooled aOR: 0.92 (0.54–1.84)] and low birth weight [pooled aOR: 0.80 (0.64–1.00)]. Anemia was not statistically significantly associated with hypertensive disorders of pregnancy regardless of stage of pregnancy [pooled OR: 0.80 (0.53–1.20)]. The relationship between anemia and perinatal mortality was inconclusive. A few studies indicated that severe maternal anemia (Hgb < 8–8.5 g/dL) was associated with increased risk of poor outcomes. We conclude that early pregnancy anemia is associated with slightly increased risk of preterm birth. The trend toward an inverse association of anemia determined during late pregnancy with preterm birth and low birth weight may reflect the benefit of plasma volume expansion.
The first complete dropsonde observation of a tropical cyclone over the South China Sea by the Hong Kong Observatory

For the first time, Hong Kong Observatory conducted a full scale dropsonde observation of the circulation of a tropical cyclone, namely, Tropical Storm Aere, on 7 October 2016, over the northern part of the South China Sea. This paper documents the observations and their use in the prediction of the track and strength of the tropical cyclone in a numerical weather prediction model. In addition to the model analysis fields, the dropsonde observations are found to provide further information about the structure of Aere. The quality of the dropsonde data was found to be satisfactory in comparison with the radiosonde data nearby. The dropsonde data were found to have a positive impact on the prediction of the track of the tropical cyclone, improving track location accuracy by about 13%. The prediction of the strength of Aere was found to have a higher dependence on the assimilation of the wind field than the assimilation of the humidity field.
Music Reduces Postoperative Pain Perception in Male Patients after Abdominal Surgery under General Anesthesia

Background: Perioperative pain after abdominal surgery is difficult to manage. Despite the advent of multimodal analgesia techniques, the opioids remain the cornerstone of treatment. Since the opioids' adverse effects are of concern immediate postoperatively, music as a modality that would influence human behavior, is of interest as an adjunct for acute pain management. Our hypothesis was that listening to instrumental music during the perioperative period reduces the pain level and decreases the use of opioids within the first 23 hours after the surgery. Methods: The study was designed as randomized clinical trial, including 54 males who underwent abdominal surgery under general anesthesia. One group was allocated to music therapy intra and postoperatively (G1), and the other was the control group (G2), without music therapy. The statistical analysis for each of the response variable, blood pressure, heart rate, oxygen saturation, visual analogue scale (VAS) score and morphine equivalents (ME), was based on a linear regression analysis accounting for group and time differences and adjusting for covariates (age, height, weight) if necessary (statistically significant). Results: Our study results show a statistically significant difference regarding the mean VAS measurements between the two groups before and after music therapy on arrival in the Postanesthesia Care Unit (PACU) [ 2.4; CI 95% 1.39-3.35 versus 4.1 CI 95% 2.77-5.53], 30 minutes [3; CI95% 2.21-3.87 vs 5.48; CI95% 4.34-6.62] and 23 hours later [2.15; CI95% 1.38-2.91 vs 4.37;CI 95% 3.51-5.24] , respectively (Table 2). There was no statistically significant difference in blood pressure (systolic and diastolic), heart rate, oxygen saturation (SpO2), and opioid consumption between the two groups at the three points in time when measurements were done. Conclusions: In this study, a short perioperative exposure to music was effective in reducing the pain perception (as measured by VAS method) but not the opioid consumption in the first 23 hours in male patients after abdominal surgery.
Analysis of small EV proteomes reveals unique functional protein networks regulated by VAP-A

Extracellular vesicles (EVs) influence cell phenotypes and functions via protein, nucleic acid and lipid cargoes. EVs are heterogeneous, due to diverse biogenesis mechanisms that remain poorly understood. Our previous study revealed that the endoplasmic rectiulum (ER) membrane contact site (MCS) linker protein VAP-A drives biogenesis of a subset of RNA-enriched EVs. Here, we examine the protein content of VAP-A-regulated EVs. Using label-free proteomics, we identified down- and up-regulated proteins in sEVs purified from VAP-A knockdown (KD) colon cancer cells. Gene set enrichment analysis (GSEA) of the data revealed protein classes that are differentially sorted to SEVs dependent on VAP-A. STRING protein-protein interaction network analysis of the RNA-binding protein (RBP) gene set identified several RNA functional machineries that are downregulated in VAP-A KD EVs, including ribosome, spliceosome, mRNA surveillance, and RNA transport proteins. We also observed downregulation of other functionally interacting protein networks, including cadherin-binding, unfolded protein binding, and ATP-dependent proteins. Significance of the study Little is known about biogenesis mechanisms that underlie EV heterogeneity. This study explores the protein repertoire of a specific subset of EVs that we recently identified to be generated at ER MCS and that are highly enriched in RNAs. We find that proteins from several classes of RNA machineries, including spliceosomes, are downregulated in EVs purified from cells knocked down for the ER MCS linker protein VAP-A. These data suggest that dynamic regulation of these protein machineries at ER MCS are involved in the sorting of RNA-RBP complexes into EVs.
Random, de novo and conserved proteins: How structure and disorder predictors perform differently

Understanding the emergence and structural characteristics of de novo and random proteins is crucial for unraveling protein evolution and designing novel enzymes. However, experimental determination of their structures remains challenging. Recent advancements in protein structure prediction, particularly with AlphaFold2 (AF2), have expanded our knowledge of protein structures, but their applicability to de novo and random proteins is unclear. In this study, we investigate the structural predictions and confidence scores of AF2 and protein language model (pLM)-based predictor ESMFold for de novo, random, and conserved proteins. We find that the structural predictions for de novo and random proteins differ significantly from conserved proteins. Interestingly, a positive correlation between disorder and confidence scores (pLDDT) is observed for de novo and random proteins, in contrast to the negative correlation observed for conserved proteins. Furthermore, the performance of structure predictors for de novo and random proteins is hampered by the lack of sequence identity. We also observe varying predicted disorder among different sequence length quartiles for random proteins, suggesting an influence of sequence length on disorder predictions. In conclusion, while structure predictors provide initial insights into the structural composition of de novo and random proteins, their accuracy and applicability to such proteins remain limited. Experimental determination of their structures is necessary for a comprehensive understanding. The positive correlation between disorder and pLDDT could imply a potential for conditional folding and transient binding interactions of de novo and random proteins.
RIM-BP2 regulates Ca2+ channel abundance and neurotransmitter release at hippocampal mossy fiber terminals

Synaptic vesicles dock and fuse at the presynaptic active zone (AZ), the specialized site for transmitter release. AZ proteins play multiple roles such as recruitment of Ca2+ channels as well as synaptic vesicle docking, priming and fusion. However, the precise role of each AZ protein type remains unknown. In order to dissect the role of RIM-BP2 at mammalian cortical synapses having low release probability, we applied direct electrophysiological recording and super-resolution imaging to hippocampal mossy fiber terminals of RIM-BP2 KO mice. By using direct presynaptic recording, we found the reduced Ca2+ currents. The measurements of EPSCs and presynaptic capacitance suggested that the initial release probability was lowered because of the reduced Ca2+ influx and impaired fusion competence in RIM-BP2 KO. Nevertheless, larger Ca2+ influx restored release partially. Consistent with presynaptic recording, STED microscopy suggested less abundance of P/Q-type Ca2+ channels at AZs deficient in RIM-BP2. Our results suggest that the RIM-BP2 regulates both Ca2+ channel abundance and transmitter release at mossy fiber synapses.
Tumor-Associated Macrophages Expand Chemoresistant, Ovarian Cancer Stem-Like Cells

The persistence of ovarian cancer stem-like cells (OvCSCs) after chemotherapy resistance has been implicated in relapse. However, the ability of these relatively quiescent cells to produce the robust tumor regrowth necessary for relapse remains an enigma. Since normal stem cells exist in a niche, and tumor-associated macrophages (TAMs) are the highest abundance immune cell within ovarian tumors, we hypothesized that TAMs may influence OvCSC proliferation. To test this, we optimized OvCSC enrichment by sphere culture and in vitro polarization of monocytes to a TAM-like M2 phenotype. Using cocultures that permitted the exchange of only soluble factors, we found that M2 macrophages increased the proliferation of sphere cells. Longer-term exposure (5-7 days) to soluble TAM factors led to retention of some stem cell features by OvCSCs but loss of others, suggesting that TAMs may support an intermediate stemness phenotype in OvCSCs. Although TAM coculture decreased the percentage of OvCSCs surviving chemotherapy, it increased the overall number. We therefore sought to determine the influence of this interaction on chemotherapy efficacy in vivo and found that inhibiting macrophages improved chemotherapy response. Comparing the gene expression changes in OvCSCs cocultured with TAMs to publicly available patient data identified 34 genes upregulated in OvCSCs by exposure to soluble TAM factors whose expression correlates with outcome. Overall, these data suggest that TAMs may influence OvCSC proliferation and impact therapeutic response.
Dynamics of pax7 expression during development, muscle regeneration, and in vitro differentiation of satellite cells in the trout

Essential for muscle fiber formation and hypertrophy, muscle stem cells, also called satellite cells, reside beneath the basal lamina of the muscle fiber. Satellite cells have been commonly localized by the expression of the Paired box 7 (Pax7) due to its specificity and the availability of antibodies in tetrapods. In fish, the identification of satellite cells remains difficult due to the lack of specific antibodies in most species. Based on the development of a highly sensitive in situ hybridization (RNAScope®) for pax7, we showed that pax7+ cells were detected in the undifferentiated myogenic epithelium corresponding to the dermomyotome at day 14 post-fertilization. Then, from day 24, pax7+ cells gradually migrated into the deep myotome and were localized along the muscle fibers and reach their niche in satellite position of the fibres after hatching. Our results showed that 18 days after muscle injury, a large number of pax7+ cells accumulated at the wound site compared to the uninjured area. During the in vitro differentiation of satellite cells, the percentage of pax7+ cells decreased from 44% to 18% on day 7, and some differentiated cells still expressed pax7. Taken together, these results show the dynamic expression of pax7 genes and the follow-up of these muscle stem cells during the different situations of muscle fiber formation in trout.
Lethal Neonatal Carnitine Palmitoyltransferase II Deficiency: An Unusual Presentation of a Rare Disorder

A term male newborn, appropriate for gestational age, developed hypo-thermia, severe cardiac dysrrhythmia, and nonoliguric hyperkalemia within 24 hours of birth. Despite the prenatal identification of cystic renal dysplasia without oligohydramnios, at birth, a solitary left leg vascular hemangioma and large palpable kidneys were the only anomalies. Gradually hypotonia, lethargy, and poor feeding developed and by 20 hours of age recurrent cardiac dysrrhythmias, myocardial dysfunction, and renal insufficiency with intermittent hyperkalemia were apparent. Episodes of apnea developed on day 7 followed by respiratory failure, recurrent cardiac dysrrhythmias, and death on day 12. Eventually laboratory and autopsy findings confirmed the diagnosis of lethal neonatal carnitine palmi-toyltransferase II deficiency
On the Gaussian Mixture Representation of the Laplace Distribution

ABSTRACT Under certain conditions, a symmetric unimodal continuous random variable ξ can be represented as a scale mixture of a standard Normal distribution Z, that is, , where the mixing distribution W is independent of Z. It is well known that if the mixing distribution is inverse Gamma, then ξ has Student’s t distribution. However, it is less well known that if the mixing distribution is Gamma, then ξ has a Laplace distribution. Several existing proofs of the latter result rely on complex calculus or nontrivial change of variables in integrals. We offer two simple and intuitive proofs based on representation and moment generating functions. As a byproduct, our proof by representation makes connections to many existing results in statistics. Supplementary materials for this article are available online.
Maternal Serum Interleukin-6, C-Reactive Protein, and Matrix Metalloproteinase-9 Concentrations as Risk Factors for Preterm Birth <32 Weeks and Adverse Neonatal Outcomes

Elevated concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and matrix metalloproteinase-9 (MMP-9) in fetal and neonatal compartments have been associated with an increased risk for preterm birth (PTB) and/or neonatal morbidity. The purpose of this study was to determine if the maternal serum concentration of IL-6, CRP, and MMP-9 in women at risk for PTB, who are not in labor and have intact membranes, are associated with an increased risk for PTB < 32 weeks and/or neonatal morbidity. Maternal serum samples collected from 475 patients enrolled in a multicenter randomized controlled trial of single versus weekly corticosteroids for women at increased risk for
A Systematic Approach to First-trimester Ultrasound Assessment of Twins

The incidence of twin pregnancies has increased for the last 20 years mainly as a result of assisted reproduction technologies and pregnancies occurring in older women. Both maternal and perinatal mortality and morbidity are increased in twin pregnancies when compared with singletons. A systematic and detailed ﬁrst-trimester ultrasound can be a useful tool for detecting chorionicity, growth discordance, and congenital malformations. Prediction of complications at an early stage can help with directing future management and counseling of patients.
Rectilinear vortex sheets of inviscid liquid-gas two-phase flow: Linear stability

The vortex sheet solutions are considered for the inviscid liquid-gas two-phase flow. In particular, the linear stability of rectilinear vortex sheets in two spatial dimensions is established for both constant and variable coefficients. The linearized problem of vortex sheet solutions with constant coefficients is studied by means of Fourier analysis, normal mode analysis, and Kreiss symmetrizer, while the linear stability with variable coefficients is obtained by Bony–Meyer paradifferential calculus theory. The linear stability is crucial to the existence of vortex sheet solutions of the nonlinear problem. A novel symmetrization and some weighted Sobolev norms are introduced to study the hyperbolic linearized problem with characteristic boundary.
(261, 105, 42) Abelian Difference Sets Do Not Exist

2015. (261, 105, 42) Abelian Diﬀerence Sets Do Not Exist. Diﬀerence sets in the group Z 3 × Z 3 × Z 37 and the group Z 3 × Z 9 × Z 7 are known not to exist. The only open abelian case with a sylow-3 subgroup rank 2 listed in Vera-Lopez and Sanchez’s [16] table is Z 3 × Z 3 × Z 29 . We prove for Vera-Lopez and Sanchez’s table that diﬀerence sets do not exist in the open group allowing the appropriate entry to be ”no”. We also prove that there exist no diﬀerence sets (261, 105, 42) for any group with order 261.
Exact solutions via invariant approach for Black‐Scholes model with time‐dependent parameters

We analyze the Black‐Scholes model with time‐dependent parameters, and it is governed by a parabolic partial differential equation (PDE). First, we compute the Lie symmetries of the Black‐Scholes model with time‐dependent parameters. It admits 6 plus infinite many Lie symmetries, and thus, it can be reduced to the classical heat equation. We use the invariant criteria for a scalar linear (1+1) parabolic PDE and obtain 2 sets of equivalence transformations. With the aid of these equivalence transformations, the Black‐Scholes model with time‐dependent parameters transforms to the classical heat equation. Moreover, the functional forms of the time‐dependent parameters in the PDE are determined via this method. Then we use the equivalence transformations and known solutions of the heat equation to establish a number of exact solutions for the Black‐Scholes model with time‐dependent parameters.
Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization

Although our understanding of the involvement of heterochromatin architectural factors in shaping nuclear organization is improving, there is still ongoing debate regarding the role of active genes in this process. In this study, we utilize publicly-available Micro-C data from mouse embryonic stem cells to investigate the relationship between gene transcription and 3D gene folding. Our analysis uncovers a nonmonotonic - globally positive - correlation between intragenic contact density and Pol II occupancy, independent of cohesin-based loop extrusion. Through the development of a biophysical model integrating the role of transcription dynamics within a polymer model of chromosome organization, we demonstrate that Pol II-mediated attractive interactions with limited valency between transcribed regions yield quantitative predictions consistent with chromosome-conformation-capture and live-imaging experiments. Our work provides compelling evidence that transcriptional activity shapes the 4D genome through Pol II-mediated micro-compartmentalization.
A Vibrating Ingestible BioElectronic Stimulator Modulates Gastric Stretch Receptors for Illusory Satiety

Effective therapies for obesity either require invasive surgical or endoscopic interventions or high patient adherence, making it challenging for the nearly 42% of American adults who suffer from obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension. Here we developed the Vibrating Ingestible BioElectronic Stimulator (VIBES) pill - an ingestible device that performs luminal vibratory stimulation to activate mechanoreceptors and stroke mucosal receptors, which induces serotonin release as well as yields a hormonal metabolic response commensurate with a fed state. We evaluated VIBES across 108 meals in swine which consistently led to diminished food intake (∼40%, p< 0.0001) and minimized the weight gain rate (p< 0.03) as compared to untreated controls. Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders.
Shared structure facilitates working memory of multiple sequences via neural replay

Daily experiences often involve the processing of multiple sequences, such as speech processing and spatial navigation, yet storing them challenges the limited capacity of working memory (WM). To achieve efficient memory storage, relational structures shared by sequences would be leveraged to reorganize and compress information. Here, participants memorized a sequence of items with different colors and spatial locations and later reproduced the full color and location sequences, one after another. Crucially, we manipulated the consistency between location and color sequence trajectories. First, sequences with consistent trajectories demonstrate improved memory performance and a trajectory correlation between the reproduced color and location sequences. Interestingly, color sequence undergoes spontaneous forward neural replay when recalling trajectory-consistent location sequence. These results reveal that shared common structure is leveraged to integrate and facilitate WM of multiple sequences through spontaneous neural replay and imply a role of common cognitive map in efficient information organization in WM.