Miracle-dz/UniFAR-FTUs huggingface dataset:
Factors Associated With Neural Tube Defects Among Newborns Delivered at Debre Berhan Specialized Hospital, North Eastern Ethiopia, 2021. Case-Control Study

Background Neural tube defects are severe congenital malformations secondary to an abnormal closure of the neural tube between third and fourth weeks of gestational ages. Neural tube defects affect birth outcomes worldwide, with an occurrence of 18.6 per 10,000 live births. In addition, neural tube defects are associated with considerable mortality, morbidity, disability, and socio-economical cost. Objective To identify factors associated with neural tube defects among newborns delivered at Debre Berhan Comprehensive Specialized Hospital, 2021. Methods Facility-based case-control study design was conducted among 381 (127 cases and 254 controls) newborns delivered from June 2019 to June 2021 at Debre Berhan Specialized Hospital. Consecutive and systematic random sampling techniques were used to select cases and controls, respectively. Data were collected using semi-structured checklists. Finally, data were entered using Epidata version 4.2. 1 and analyzed using SPSS version 25. In the bivariable logistic regression model, factors with a p < 0.20 were entered into multivariable logistic regressions. Statistical significance was declared at a p < 0.05. Result In this study, 381 newborns (127 cases and 254 controls) participated with a response rate of 100%. In the logistic regression model, mothers who took medication during pregnancy [AOR 1.83 (95% CI 1.08–3.08)], mothers who did not take a balanced diet during pregnancy [AOR 13.46 (95% CI 7.83–23.13)], and mothers who did not take folic acid before and during the first trimester of pregnancy [AOR 1.71 (95% CI 1.01–2.94)] were significantly associated with neural tube defect. Conclusion and Recommendation Mothers who took medication during pregnancy, mothers who did not take balanced diets during pregnancy, and mothers who did not take folic acid during pregnancy were the significant factors of neural tube defects. Health care professionals should focus on maternal safe drug prescription, maternal folate intake, and a balanced diet before and during pregnancy.
Patients' Perception of the Use of the EasyPod™ Growth Hormone Injector Device and Impact on Injection Adherence: A Multi-Center Regional Study

Objective This study aimed to assess patient perceptions of the use of the EasyPod™ growth hormone delivery device and its association with compliance. Methods This cross-sectional, multicenter study was conducted in six centers from three countries (United Arab Emirates, Oman, and Saudi Arabia,) between March 2020 and June 2020. Children and adolescents aged 3–18 years, diagnosed with growth disorders and receiving rhGH through the EasyPod™ device were enrolled. Patients and caregivers were given a pre-set questionnaire that evaluated patient satisfaction, preference for technical and personalized features, and device drawbacks. The results were analyzed using independent measures of analysis of variance to evaluate the association of higher satisfaction with device features and better compliance. Results A total of 186 patients were enrolled in the study. Of these, 45.7% had GH deficiency. The mean age (±SD) of patients was 11.8 (±2.76) years; 117 (62.90%) were males. Average compliance was 87%. One hundred patients (53.76%) had injection compliance of ≥90%. Amongst these patients, 74%, 68%, and 77% top-scored (5/5) the technical features of hidden needle, skin sensor, and pre-set dosing, respectively, compared to top scores by 39%, 34%, and 51% patients in the <90% compliance group (p-value <0.05). Similarly, a statistically significant difference was observed between the groups (p-value <0.05) in the perception of the usefulness of the tracking features such as display of history of injected doses (78% vs. 47.7%), a reminder for medicine remaining (46% vs. 23.3%) and battery power indicator (48% vs. 20.9%). Personal screen messages were associated with higher compliance while the requirement to keep the device in the fridge was reported as the most inconvenient feature by 56% of patients in the higher compliance group as against 39.5% in the lower compliance group (p-value <0.05). There was no statistically significant difference in the intensity of pain reported in the two compliance groups. Conclusion Our study showed that there is a statistically significant association between better perception of device features and higher compliance.
Molecular Signatures Correlated With Poor IVF Outcomes: Insights From the mRNA and lncRNA Expression of Endometriotic Granulosa Cells

The outcomes of in vitro fertilization (IVF) for endometriotic women are significantly worse than for patients without ovarian endometriosis (OEM), as shown by fewer retrieved oocytes. However, the exact pathophysiological mechanism is still unknown. Thus, we conducted a prospective study that analyzed mRNA and lncRNA transcriptome between granulosa cells (GCs) from patients with fewer retrieved oocytes due to OEM and GCs from controls with male factor (MF) infertility using an RNA sequencing approach. We found a group of significantly differentially expressed genes (DEGs), including NR5A2, MAP3K5, PGRMC2, PRKAR2A, DEPTOR, ITGAV, KPNB1, GPC6, EIF3A, and SMC5, which were validated to be upregulated and negatively correlated with retrieved oocyte numbers in GCs of patients with OEM, while DUSP1 demonstrated the opposite. The molecular functions of these DEGs were mainly enriched in pathways involving mitogen-activated protein kinase (MAPK) signaling, Wnt signaling, steroid hormone response, apoptosis, and cell junction. Furthermore, we performed lncRNA analysis and identified a group of differentially expressed known/novel lncRNAs that were co-expressed with the validated DEGs and correlated with retrieved oocyte numbers. Co-expression networks were constructed between the DEGs and known/novel lncRNAs. These distinctive molecular signatures uncovered in this study are involved in the pathological regulation of ovarian reserve dysfunction in OEM patients.
Antigen Reactivity and Clinical Significance of Autoantibodies Directed Against the Pyruvate Dehydrogenase Antigen Complex in Patients With Connective Tissue Disease

Introduction Antimitochondrial antibodies (AMAs) are the hallmark of primary biliary cholangitis (PBC) but can be identified also in patients with connective tissue disease, namely, systemic sclerosis (SSc). Protein immunoprecipitation (IP) and IP-Western blot (WB) can be used to confirm AMA positivity directed at the pyruvate dehydrogenase complex (PDC) subunits E1α, E1β, E2/E3, and E3BP in patients showing a cytoplasmic reticular pattern at indirect immunofluorescence when performed in a screening setting before the onset of overt cholestasis in rheumatic patients. Patients and Methods We studied sera from 285 patients affected by connective tissue disease [SSc, n = 144; dermato/polymyositis (DM/PM), n = 56; and undifferentiated connective tissue disease (UCTD), n = 85] by indirect immunofluorescence (IIF), protein-IP, and IP-WB to identify specific PDC subunits recognized by AMA. Results Twenty percent (57/285) of sera from patients with connective tissue disease had a cytoplasmic reticular pattern at IIF, and in 77% (44/57, including 20 SSc, 12 PM/DM, and 12 UCTD) of these, we detected different titers of autoantibodies against the PDC subunits, specifically against PDC-E2. Among these sera, 4 (9%) tested positive for anti-E1α, 15 (34%) for anti-E1β, and 16 (36%) for anti-E3BP. Four of the 20 AMA-positive SSc cases (20%) had been already diagnosed with PBC, and all were positive for autoantibodies against the subunits PDC-E2, E3, and E3BP. Conclusions Using IIF and IP, we confirm that autoantibodies against the PDC components are detected in rheumatic patients with PBC or without liver dysfunction. In view of the strong predictive value of AMA for PBC, a strict follow-up of these latter patients is warranted for an early diagnosis of the disease.
Association Between Adipose Tissue Proton Density Fat Fraction, Resting Metabolic Rate and FTO Genotype in Humans

Background The difference of proton density fat fraction (PDFF) between supraclavicular and gluteal adipose tissue might indicate the presence of brown adipose tissue (BAT). Aim of this cross-sectional study was to investigate the association between PDFF over the supraclavicular fat region as a proxy of BAT proportion and resting metabolic rate (RMR). In addition, the association between the single nucleotide polymorphism (SNP) rs1421085 at the fat mass and obesity associated (FTO) gene locus and both PDFF and RMR was investigated. Methods Anthropometric, clinical, and lifestyle data from 92 healthy adults (66.3% females, mean age: 36.2 ± 13.0 years, mean body mass index: 24.9 ± 5.4 kg/m2) were included in the analysis. The RMR was measured by indirect calorimetry. The magnetic resonance imaging (MRI) was used for the measurement of visceral and subcutaneous adipose tissue (VAT, SAT) volumes and for the measurement of adipose tissue PDFF. Results Mean RMR of the whole group was 1 474.8 ± 242.2 kcal. Genotype data was available for 90 participants. After adjustment for age, sex, weight change and fat-free mass (FFM), no association was found between supraclavicular PDFF (p = 0.346) and gluteal PDFF (p = 0.252), respectively, and RMR, whereas statistically significant evidence for a negative association between delta PDFF (difference between gluteal PDFF and supraclavicular PDFF) and RMR (p = 0.027) was obtained. No statistically significant evidence was observed for per FTO risk allele change in RMR, gluteal and supraclavicular PDFF maps or volumes of VAT and SAT. Conclusions Supraclavicular PDFF as a surrogate marker of BAT presence is not a determinant of RMR under basal conditions. In the present study, the FTO rs1421085 variant is not associated with either RMR or PDFF. Further studies are needed to elucidate the effect of BAT on RMR.
Case Report: Opportunities and Challenges of Immunotherapy in Heavily-Treated EGFR-Mutant Advanced Squamous Cell Lung Carcinoma After Progression on EGFR-TKIs and Chemotherapy

Background Epidermal growth factor receptor (EGFR) mutations have a low incidence in squamous cell lung cancer (SqCLC), and the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated SqCLC is far less than that in EGFR-mutated lung adenocarcinoma. The treatment strategy for patients with EGFR-mutated non-small cell lung cancer who are refractory to EGFR TKIs has become a current dilemma and challenge. Case Presentation A case of a 69-year-old male patient suffering from intermittent cough and hemoptysis was diagnosed with EGFR-mutated advanced SqCLC (stage cT2bN2M1). The patient was treated with camrelizumab alone after five courses of different systemic therapies and achieved a partial response, with an eminent progression-free survival of more than 24 months. Grade 1 to 2 reactive cutaneous capillary endothelial proliferation and mild pruritus were observed during the treatment. No other immune-related adverse events were observed. Conclusion Monotherapy of immune-checkpoint inhibitors may be considered as a later-line option for EGFR-mutated advanced SqCLC patients with PD-L1 expression.
Serum Abnormal Metabolites for Evaluating Therapeutic Response and Prognosis of Patients With Multiple Myeloma

Aims To evaluate abnormal metabolites related to treatment response and prognosis of multiple myeloma (MM) patients through ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS). Methods Forty-six symptomatic MM patients were included in this study who had a prior high level of positive monoclonal proteins before receiving targeted therapy with bortezomib-based regimens. UPLC-MS along with traditional immunofixation was performed on MM diagnostic samples and effective serum samples, and UPLC-MS was used to target valuable metabolic markers related to M protein.MM patients were segregated into pre-therapy (pre-T) and post-therapy (post-T) groups according to the response after chemotherapy. A monoclonal protein could be detected at baseline in 33 newly diagnosed MM (NDMM), 13 refractory and relapsed MM (RRMM) patients and 20 healthy controls (HC) by immunofixation. Results Between pre-T and post-T patients, the data showed that 32, 28 and 3 different metabolites were significantly correlated with M protein in IgG, IgA and light chain-type MM, respectively. These identified metabolites were significantly enriched in arginine and proline metabolism as well as glycerophospholipid metabolism pathways. Among them, PC (19:0/22:2) was displayed to increase significantly and consistently with M protein in each subtype of MM after treatment, which obviously indicated that it was related to the treatment response of MM. Further survival analysis of metabolic markers found that aspartic acid, LysoPE (16:0), SM (d18:1/17:0), PC (18:0/24:1), PC (16:0/16:0), TG (18:1/18:1/22:5) and LysoPE (18:2) reaching a certain cutoff value may be associated with shorter progression free survival (PFS). Finally, Cox multivariate regression analysis identified three factors were independent prognostic factors of MM. Moreover, there were significantly different in PC (19:0/22:2) and in aspartic acid between MM patients and healthy people. Conclusion This work identified significant metabolic disorders in 46 pairs off pre- and post-therapy MM patients, specifically in arginine, proline and glycerophospholipid pathways. The abnormal metabolites have the potential to serve as new biomarkers for evaluating treatment response and prognosis, as well as early monitoring of disease activity. Therefore, these systematic studies on abnormal metabolites as biomarkers for diagnosis and treatment will provide the evidence for future precise treatment of MM.
Supporting Artificial Social Intelligence With Theory of Mind

In this paper, we discuss the development of artificial theory of mind as foundational to an agent's ability to collaborate with human team members. Agents imbued with artificial social intelligence will require various capabilities to gather the social data needed to inform an artificial theory of mind of their human counterparts. We draw from social signals theorizing and discuss a framework to guide consideration of core features of artificial social intelligence. We discuss how human social intelligence, and the development of theory of mind, can contribute to the development of artificial social intelligence by forming a foundation on which to help agents model, interpret and predict the behaviors and mental states of humans to support human-agent interaction. Artificial social intelligence will need the processing capabilities to perceive, interpret, and generate combinations of social cues to operate within a human-agent team. Artificial Theory of Mind affords a structure by which a socially intelligent agent could be imbued with the ability to model their human counterparts and engage in effective human-agent interaction. Further, modeling Artificial Theory of Mind can be used by an ASI to support transparent communication with humans, improving trust in agents, so that they may better predict future system behavior based on their understanding of and support trust in artificial socially intelligent agents.
Changes in Physiological Tendon Substrate Stiffness Have Moderate Effects on Tendon-Derived Cell Growth and Immune Cell Activation

Tendinopathy is characterised by pathological changes in tendon matrix composition, architecture, and stiffness, alterations in tendon resident cell characteristics, and fibrosis, with inflammation also emerging as an important factor in tendinopathy progression. The sequence of pathological changes in tendinopathy and the cellular effects of the deteriorating matrix are largely unknown. This study investigated the effects of substrate stiffness on tendon-derived cells (TDCs) and THP-1 macrophages using PDMS substrates representing physiological tendon stiffness (1.88 MPa), a stiff gel (3.17 MPa) and a soft gel (0.61 MPa). Human TDCs were cultured on the different gel substrates and on tissue culture plastic. Cell growth was determined by alamarBlue™ assay, cell morphology was analysed in f-actin labelled cells, and phenotypic markers were analysed by real-time PCR. We found that in comparison to TDCs growing on gels with physiological stiffness, cell growth increased on soft gels at 48 h (23%, p = 0.003). Cell morphology was similar on all three gels. SCX expression was slightly reduced on the soft gels (1.4-fold lower, p = 0.026) and COL1A1 expression increased on the stiff gels (2.2-fold, p = 0.041). Culturing THP-1 macrophages on soft gels induced increased expression of IL1B (2-fold, p = 0.018), and IL8 expression was inhibited on the stiffer gels (1.9-fold, p = 0.012). We also found that culturing TDCs on plastic increased cell growth, altered cell morphology, and inhibited the expression of SCX, SOX9, MMP3, and COL3. We conclude that TDCs and macrophages respond to changes in matrix stiffness. The magnitude of responses measured in TDCs were minor on the range of substrate stiffness tested by the gels. Changes in THP-1 macrophages suggested a more inflammatory phenotype on substrates with non-physiological stiffness. Although cell response to subtle variations in matrix stiffness was moderate, it is possible that these alterations may contribute to the onset and progression of tendinopathy.
Single-Cell RNA-Seq Analysis Reveals Macrophage Involved in the Progression of Human Intervertebral Disc Degeneration

Intervertebral disc degeneration (IDD) has been considered as the primary pathological mechanism that underlies low back pain. Understanding the molecular mechanisms underlying human IDD is imperative for making strategies to treat IDD-related diseases. Herein, we report the molecular programs, lineage progression patterns, and paths of cellular communications during the progression of IDD using single-cell RNA sequencing (scRNA-seq) on nucleus pulposus (NP) cells from patients with different grades of IDD undergoing discectomy. New subtypes of cells and cell-type-specific gene signatures of the metabolic homeostatic NP cells (Met NPC), adhesive NP cells (Adh NPC), inflammatory response NP cells (IR NPC), endoplasmic reticulum stress NP cells (ERS NPC), fibrocartilaginous NP cells (Fc NPC), and CD70 and CD82+ progenitor NP cells (Pro NPC) were identified. In the late stage of IDD, the IR NPC and Fc NPC account for a large proportion of NPC. Importantly, immune cells including macrophages, T cells, myeloid progenitors, and neutrophils were also identified, and further analysis showed that significant intercellular interaction between macrophages and Pro NPC occurred via MIF (macrophage migration inhibitory factor) and NF-kB signaling pathways during the progression of IDD. In addition, dynamic polarization of macrophage M1 and M2 cell subtypes was found in the progression of IDD, and gene set functional enrichment analysis suggested a significant role of the macrophage polarization in regulating cell metabolism, especially the Pro NPC. Finally, we found that the NP cells in the late degenerative stage were mainly composed of the cell types related to inflammatory and endoplasmic reticulum (ER) response, and fibrocartilaginous activity. Our results provided new insights into the identification of NP cell populations at single-cell resolution and at the relatively whole-transcriptome scale, accompanied by cellular communications between immune cells and NP cells, and discriminative markers in relation to specific cell subsets. These new findings present clues for effective and functional manipulation of human IDD-related bioremediation and healthcare.
Music Perception Abilities and Ambiguous Word Learning: Is There Cross-Domain Transfer in Nonmusicians?

Perception of music and speech is based on similar auditory skills, and it is often suggested that those with enhanced music perception skills may perceive and learn novel words more easily. The current study tested whether music perception abilities are associated with novel word learning in an ambiguous learning scenario. Using a cross-situational word learning (CSWL) task, nonmusician adults were exposed to word-object pairings between eight novel words and visual referents. Novel words were either non-minimal pairs differing in all sounds or minimal pairs differing in their initial consonant or vowel. In order to be successful in this task, learners need to be able to correctly encode the phonological details of the novel words and have sufficient auditory working memory to remember the correct word-object pairings. Using the Mistuning Perception Test (MPT) and the Melodic Discrimination Test (MDT), we measured learners’ pitch perception and auditory working memory. We predicted that those with higher MPT and MDT values would perform better in the CSWL task and in particular for novel words with high phonological overlap (i.e., minimal pairs). We found that higher musical perception skills led to higher accuracy for non-minimal pairs and minimal pairs differing in their initial consonant. Interestingly, this was not the case for vowel minimal pairs. We discuss the results in relation to theories of second language word learning such as the Second Language Perception model (L2LP).
Identification of Predictive Factors for Lymph Node Metastasis in pT1 Stage Colorectal Cancer Patients: A Retrospective Analysis Based on the Population Database

Objective: The purpose of this study was to identify predictive factors for lymph node metastasis (LNM) in pT1 stage colorectal cancer (CRC) patients. Methods: From the Surveillance, Epidemiology, and End Results (SEER) database, 2,697 consecutive pT1 stage patients who underwent surgical resection were retrospectively reviewed. Predictive factors for LNM were identified by the univariate and multivariate logistic regression analysis. The Kaplan-Meier curves and multivariate Cox regression analysis were used to evaluate the relationships between LNM and overall survival (OS) as well as cancer specific survival (CSS) of pT1 stage CRC patients. Results: The prevalence of LNM in pT1 stage CRC patients was 15.2% (410/2,697). Patient age <60 years (OR:1.869, 95% CI: 1.505–2.321, p < 0.001), poorly differentiated or mucinous or signet ring cell adenocarcinoma (OR:2.075, 95% CI: 1.584–2.717, p < 0.001), elevated carcinoembryonic antigen (CEA) level (OR:1.343, 95% CI: 1.022–1.763, p = 0.033) and perineural invasion (PNI) (OR:6.212, 95% CI: 3.502–11.017, p < 0.001) were significantly associated with LNM in pT1 stage patients. The survival analysis demonstrated that pT1 stage patients with LNM had a worse OS (5-year OS: 82.2% vs 88.7%, p = 0.020) and CSS (5-year CSS: 74.9% vs 81.5%, p = 0.041) than those without lymph node metastasis. Lymph node metastasis was an independent predictor of poor OS (HR: 1.543, 95% CI: 1.156–2.060, p = 0.003) and CSS (HR: 1.614, 95% CI: 1.121–2.324, p = 0.010) for pT1 stage colorectal cancer patients. Conclusion: Age, differentiation type, CEA level and perineural invasion were independent predictive factors for LNM in pT1 stage CRC patients. These findings might provide further risk stratification for pT1 stage patients and help clinicians identify high-risk individuals.