Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms for regulation of RAS palmitoylation and plasma membrane trafficking in hematopoietic malignancies

Palmitoylation is a critical posttranslational modification that enables the cellular membrane localization and subsequent activation of RAS proteins, including HRAS, KRAS, and NRAS. However, the molecular mechanism that regulates RAS palmitoylation in malignant diseases remains unclear. In this issue of the JCI, Ren, Xing, and authors shed light on this topic and revealed how upregulation of RAB27B, as a consequence of CBL loss and Janus kinase 2 (JAK2) activation, contributes to leukemogenesis. The authors found that RAB27B mediated NRAS palmitoylation and plasma membrane localization by recruiting ZDHHC9. The findings suggest that targeting RAB27B could provide a promising therapeutic strategy for NRAS-driven cancers.
Design of Adaptive Switching Controller for Robotic Manipulators with Disturbance

Two adaptive switching control strategies are proposed for the trajectory tracking problem of robotic manipulator in this paper. The first scheme is designed for the supremum of the bounded disturbance for robot manipulator being known; while the supremum is not known, the second scheme is proposed. Each proposed scheme consists of an adaptive switching law and a PD controller. Based on the Lyapunov stability theorem, it is shown that two new schemes can guarantee tracking performance of the robotic manipulator and be adapted to the alternating unknown loads. Simulations for two-link robotic manipulator are carried out and show that the two schemes can avoid the overlarge input torque, and the feasibility and validity of the proposed control schemes are proved.
A multiresolution stereopsis algorithm based on the Gabor representation

A new approach to the stereopsis problem, based on the frequency domain has been described. It has been shown that a multiresolution 'coarse-fine' algorithm, based on a spatially localised frequency domain (Gabor) representation, can lead to unbiased depth estimates and is capable of being implemented in a fast algorithm, using a pyramidal image representation. The performance of the algorithm has been explored statistically and through experimental tests and has been found satisfactory.
The agential perspective: Countermapping the modern synthesis

We compare and contrast two theoretical perspectives on adaptive evolution—the orthodox Modern Synthesis perspective, and the nascent Agential Perspective. To do so, we develop the idea from Rasmus Grønfeldt Winther of a ‘countermap’, as a means for comparing the respective ontologies of different scientific perspectives. We conclude that the modern Synthesis perspective achieves an impressively comprehensive view of a universal set of dynamical properties of populations, but at the considerable cost of radically distorting the nature of the biological processes that contribute to evolution. For its part, the Agential Perspective offers the prospect of representing the biological processes of evolution with much greater fidelity, but at the expense of generality. Trade‐offs of this sort are endemic to science, and inevitable. Recognizing them helps us to avoid the pitfalls of ‘illicit reification’, i.e. the mistake of interpreting a feature of a scientific perspective as a feature of the non‐perspectival world. We argue that much of the traditional Modern Synthesis representation of the biology of evolution commits this illicit reification.
Early life corticosteroid overexposure: Epigenetic and fetal origins of adult diseases

The relationship between events occurring during intrauterine development and later‐life predisposition to long‐term disease, has been described. The fetus responds to excess intrauterine exposure to high levels of corticosteroids, modifying their physiological development and stopping their growth. Fetal exposure to elevated levels of either endogenous (alterations in fetal hypothalamic‐pituitary‐adrenal axis) or synthetic corticosteroids, is one model of early‐life adversity; to developing adult disease. At the molecular level, there are transcriptional changes in metabolic and growth pathways. Epigenetic mechanisms participate in transgenerational inheritance, not genomic. Exposures that change 11β‐hydroxysteroid dehydrogenase type 2 enzyme methylation status in the placenta can result in transcriptional repression of the gene, causing the fetus to be exposed to higher levels of cortisol. More precise diagnosis and management of antenatal corticosteroids for preterm birth, would potentially decrease the risk of long‐term adverse outcomes. More studies are needed to understand the potential roles of factors to alter fetal corticosteroid exposure. Long‐term infant follow‐up is required to determine whether methylation changes in placenta may represent useful biomarkers of later disease risk. This review, summarize recent advances in the programming of fetal effects of corticosteroid exposure, the role of corticosteroids in epigenetic gene regulation of placental 11β‐hydroxysteroid dehydrogenase type 2 enzyme expression and transgenerational effects.
Testing for Independence in Intraclass Contingency Tables

An intraclass contingency table is obtained from an ordinary square table by pooling the frequencies of cells corresponding to the same pair of categories. Methods for the estimation of parameters and for testing for independence and quasi-independence in intraclass tables are discussed and illustrated. Under the assumption of symmetry, gain in power is achieved by using the intraclass table even if the full table is known.
Cerebrospinal fluid CXCL13 in non-borrelial central nervous system infections: contribution of CXCL13 to the differential diagnosis

Abstract Background The chemokine CXCL13 in cerebrospinal fluid (CSF) is used as a diagnostic marker of Lyme neuroborreliosis (LNB). However, the elevated levels in other non-borrelial CNS infections and the lack of a clearly defined cut-off value are limitations of the test. Methods In our prospective study, we evaluated CSF CXCL13 levels in patients with LNB (47 patients), tick-borne encephalitis (TBE; 46 patients), enteroviral CNS infections (EV; 45 patients), herpetic CNS infections (HV; 23 patients), neurosyphilis (NS; 11 patients) and controls (46 patients). The correlation of CXCL13 with CSF mononuclears was determined in all groups. Results Median CXCL13 was significantly higher in LNB group; however, the cut-off value of 162 pg/mL was also exceeded in 22% of TBE patients, 2% EV patients, 44% HV patients and in 55% patients with NS. Sensitivity and specificity were 0.83 and 0.78, respectively, with a Youden index of 0.62. CXCL13 was significantly correlated with CSF mononuclears (p = .0024), but the type of infectious agent had a greater influence on CXCL13 levels. Conclusions Increased CXCL13 levels are useful for LNB diagnostics, but other non-purulent CNS infections causes should be considered if intrathecal synthesis of borrelia specific antibodies is not confirmed or clinical manifestations are atypical.
RSS-Based Localization via Bayesian Ranging and Iterative Least Squares Positioning

In the framework of range-based localization from RSS(received signal strength)measurements,the Bayesian Ranging and Iterative Least Squares(ILS)positioning is proposed in this paper.In ranging phase,ranging is considered as a Bayesian estimation problem,and the distance is estimated by MMSE(minimum mean square error). In positioning phase,,ILS is used to update the estimated of unknown position.Numerical results show that the proposed algorithm improves considerably the accuracy of localization,and reduces computational complexity,but increases computation time.
DOT1L bridges transcription and heterochromatin formation at mammalian pericentromeres

Repetitive DNA elements are packaged in heterochromatin, but many require bursts of transcription to initiate and maintain long‐term silencing. The mechanisms by which these heterochromatic genome features are transcribed remain largely unknown. Here, we show that DOT1L, a conserved histone methyltransferase that modifies lysine 79 of histone H3 (H3K79), has a specialized role in transcription of major satellite repeats to maintain pericentromeric heterochromatin and genome stability. We find that H3K79me3 is selectively enriched relative to H3K79me2 at repetitive elements in mouse embryonic stem cells (mESCs), that DOT1L loss compromises pericentromeric satellite transcription, and that this activity involves possible coordination between DOT1L and the chromatin remodeler SMARCA5. Stimulation of transcript production from pericentromeric repeats by DOT1L participates in stabilization of heterochromatin structures in mESCs and cleavage‐stage embryos and is required for preimplantation viability. Our findings uncover an important role for DOT1L as a bridge between transcriptional activation of repeat elements and heterochromatin stability, advancing our understanding of how genome integrity is maintained and how chromatin state is set up during early development.
Primordial follicles remaining in young cancer survivors who received chemotherapy

Ovarian tissue cryopreservation (OTC) is performed for fertility preservation in cancer patients undergoing chemotherapy. Although anti‐Müllerian hormone is used as a marker for ovarian reserve, serum levels do not always correlate with the number of follicles. Additionally, the follicle development stage most affected by chemotherapy is unclear. We examined the association between serum anti‐Müllerian hormone levels and the number of remaining primordial follicles after chemotherapy, as well as which follicle stage is most affected by chemotherapy before ovarian cryopreservation.
Perspectives of psychiatric trainees and examiners on the assessment of communication skills during an online clinical examination: a qualitative study.

BACKGROUND Effective doctor-patient communication is a core competency for healthcare professionals. With the pivot to online clinical education and assessment due to the COVID-19 pandemic, there was a need to explore the views of psychiatric trainees and examiners on assessment of communication skills during online high stakes postgraduate examinations. METHODS The study was designed as descriptive qualitative research. All candidates and examiners of the September and November 2020 sitting of online Basic Specialist Training exam (a clinical Objective Structured Clinical Examination exam completed in the first 4 years of psychiatry training) were invited to participate. The respondents were interviewed by Zoom which was transcribed verbatim. Data were analyzed by NVivo20 pro and various themes and subthemes were drawn using Braun and Clarke thematic analysis. RESULTS A total of seven candidates and seven examiners were interviewed with an average duration of 30 minutes and 25 minutes, respectively. Four main themes emerged: Communication, Screen optimization, Continuation postpandemic and Overall experience. All candidates preferred to continue an online format post pandemic for practical reasons e.g., avoiding travel and overnight stay, while all examiners preferred to go back to in-person Objective Structured Clinical Examination. However, continuation of online Clinical Formulation and Management Examination was agreed by both groups. CONCLUSION The participants were largely satisfied with the online examination but did not consider it equal to face-to-face for picking up nonverbal cues. Overall minimal technical issues were reported. These findings may be helpful to modify current psychiatry membership examinations or similar assessments in other countries and specialties.
Predicting phonological information in language comprehension: evidence from ERP representational similarity analysis and Chinese idioms

Abstract Do comprehenders predict the meaning and even the phonological form of upcoming words during language comprehension? With a growing body of evidence suggesting that semantic representations may be predicted, the evidence for phonological prediction is less clear and largely derived from studies conducted in languages utilizing an alphabetic script. In this research, we aim to examine the prediction of phonological information in the processing of Chinese idioms through the use of ERP representational similarity analysis (RSA). The study utilizes four-character Chinese idioms, and phonological overlap was manipulated by varying the syllable at the idiom-final part between idiom pairs so that pairs of idioms share a syllable (i.e. within-pairs) or not (between-pairs). We quantified the similarity between patterns of neural activity of idioms for within- and between-pairs. RSA results revealed greater similarity in neural activity patterns for idioms within-pairs, compared with between-pairs, and critically this similarity effect was observed prior to the presentation of the phonological similarity, providing evidence for the pre-activation of upcoming phonological information, under circumstances that encourage predictive processing.
Succinate metabolism and membrane reorganization drives the endotheliopathy and coagulopathy of traumatic hemorrhage

Acute hemorrhage commonly leads to coagulopathy and organ dysfunction or failure. Recent evidence suggests that damage to the endothelial glycocalyx contributes to these adverse outcomes. The physiological events mediating acute glycocalyx shedding are undefined, however. Here, we show that succinate accumulation within endothelial cells drives glycocalyx degradation through a membrane reorganization-mediated mechanism. We investigated this mechanism in a cultured endothelial cell hypoxia-reoxygenation model, in a rat model of hemorrhage, and in trauma patient plasma samples. We found that succinate metabolism by succinate dehydrogenase mediates glycocalyx damage through lipid oxidation and phospholipase A2-mediated membrane reorganization, promoting the interaction of matrix metalloproteinase 24 (MMP24) and MMP25 with glycocalyx constituents. In a rat hemorrhage model, inhibiting succinate metabolism or membrane reorganization prevented glycocalyx damage and coagulopathy. In patients with trauma, succinate levels were associated with glycocalyx damage and the development of coagulopathy, and the interaction of MMP24 and syndecan-1 was elevated compared to healthy controls.
Evaluation of the Lingual Splitting Patterns and the Lateral Bone Cut Ends Following Mandibular Bilateral Sagittal Split Osteotomy Using Cone Beam Computed Tomography (CBCT)

The bilateral sagittal split osteotomy (BSSO) is the most popular orthognathic procedure performed by maxillofacial surgeons to treat skeletal class II and class III and to correct mandibular asymmetries. The study aimed to evaluate the lingual splitting patterns and lateral bone cut end (LBCE) in bilateral sagittal split osteotomy (BSSO) and their relation with the ramal thickness and the presence of impacted third molars using cone beam computed tomography (CBCT). This prospective observational study included patients with mandibular prognathism who were treated with BSSO with or without Le Fort I osteotomy. Cone beam computed tomography was used to measure the ramal thickness preoperatively and to evaluate the LBCE, and the lingual splitting patterns postoperatively. Twenty-one patients (42 sides) were included in this study. The most commonly observed lingual splitting pattern was type III (47.6%), while the most common LBCE was type B (59.5%). The bad split was encountered 8 times on 42 sides (16.7%). A nonsignificant relationship between the ramal thickness and bad splitting was observed (P=0.901). Impacted third molars were present in 16 of the 42 sides (38.1%) and had no significant effect on the occurrence of bad splitting (P=0.063). Type III lingual splitting pattern and type B LBCE were the most commonly observed patterns. No direct association was observed concerning the presence of impacted mandibular third molars and the thickness of the ramus with the occurrence of bad splitting.
NANOG is required to establish the competence for germ-layer differentiation in the basal tetrapod axolotl

Pluripotency defines the unlimited potential of individual cells of vertebrate embryos, from which all adult somatic cells and germ cells are derived. Understanding how the programming of pluripotency evolved has been obscured in part by a lack of data from lower vertebrates; in model systems such as frogs and zebrafish, the function of the pluripotency genes NANOG and POU5F1 have diverged. Here, we investigated how the axolotl ortholog of NANOG programs pluripotency during development. Axolotl NANOG is absolutely required for gastrulation and germ-layer commitment. We show that in axolotl primitive ectoderm (animal caps; ACs) NANOG and NODAL activity, as well as the epigenetic modifying enzyme DPY30, are required for the mass deposition of H3K4me3 in pluripotent chromatin. We also demonstrate that all 3 protein activities are required for ACs to establish the competency to differentiate toward mesoderm. Our results suggest the ancient function of NANOG may be establishing the competence for lineage differentiation in early cells. These observations provide insights into embryonic development in the tetrapod ancestor from which terrestrial vertebrates evolved.
Subclassification of epithelioid sarcoma with potential therapeutic impact

Epithelioid sarcoma is a rare and aggressive mesenchymal tumour, the genetic hallmark of which is the loss of expression of SMARCB1, a key member of the SWItch/Sucrose Non‐Fermentable (SWI/SNF) chromatin remodelling complex. Hampered by its rarity, epithelioid sarcoma has received little research attention and therapeutic options for this disease remain limited. SMARCB1‐deficient tumours also include malignant rhabdoid tumour, atypical teratoid and rhabdoid tumour, epithelioid malignant peripheral nerve sheath tumour, and poorly differentiated chordoma. Histologically, it can be challenging to distinguish epithelioid sarcoma from malignant rhabdoid tumour and other SMARCB1‐deficient tumours, whereas methylation profiling shows that they represent distinct entities and facilitates their classification. Methylation studies on SMARCB1‐deficient tumours, although not including epithelioid sarcomas, reported methylation subgroups which resulted in new clinical stratification and therapeutic approaches. In addition, emerging evidence indicates that immunotherapy, including immune checkpoint inhibitors, represents a promising therapeutic strategy for SMARCB1‐deficient tumours. Here, we show that some epithelioid sarcomas share methylation patterns of malignant rhabdoid tumours indicating that this could help to distinguish these entities and guide treatment. Using gene expression data, we also showed that the immune environment of epithelioid sarcoma is characterised by a predominance of CD8+ lymphocytes and M2 macrophages. These findings have potential implications for the management of patients with epithelioid sarcoma. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Perceived Knowledge, Attitudes, and Barriers Toward the Adoption of Telemedicine Services in the Kingdom of Saudi Arabia: Cross-Sectional Study

Background The adoption of telemedicine has facilitated the opportunity to offer the best health care services. Nevertheless, there is a mismatch between the presence of telemedicine programs in the Kingdom of Saudi Arabia and poor acceptance by the end-user patients. Objective This study aimed to gain a holistic understanding of the knowledge, attitudes, and barriers of the end-user patients (ie, research participants) toward the utility of telemedicine services in the Kingdom of Saudi Arabia. Methods A cross-sectional, survey-based study was conducted from June 1 to July 31, 2022, in the Kingdom of Saudi Arabia. The questionnaire was developed based on a literature review and was examined for validity and reliability. Knowledge questions used a yes-or-no format, whereas attitude and barrier questions used a 5-point Likert-scale format. Data were reported descriptively and analyzed using SPSS (IBM Corp) software. To evaluate the differences in mean scores and identify sociodemographic factors associated with knowledge and attitudes toward the adoption of telemedicine, the data were analyzed using univariate and multivariable regression analyses, respectively. Results Overall, 1024 participants participated in the survey. The percentages of participants who attended a telemedicine service before, during, and after COVID-19 were 49.61% (508/1024), 61.91% (634/1024), and 50.1% (513/1024), respectively. The mean score for knowledge was 3.52 (SD 1.486; range 0-5), reflecting a high level of knowledge. The mean score for attitudes was 37.08 (SD 8.526; range 11-55), reflecting optimistic (positive) attitudes. Regarding barriers, the participants voiced some concerns regarding patient and physician resistance and attributed some cultural and technology-related limitations as potential hindrances to the full adoption of telemedicine services. The place of residence (rural vs nonrural) had a significant impact on the scores of knowledge, attitudes, and barriers, whereas gender had no significant impact. The multivariable regression analysis showed that several sociodemographic factors significantly correlated with knowledge and attitudes toward the adoption of telemedicine services. Conclusions The participants showed good knowledge and positive attitudes toward telemedicine services. The perceived barriers were in line with the published literature. This research calls for the need to strengthen the positive attitudes and rectify the barriers, so that the utility of telemedicine services can be maximized in the community.
The effect of circulating adiponectin levels on incident gestational diabetes mellitus: systematic review and meta‑analysis

Abstract Background To quantitatively synthesize evidence from prospective observational studies regarding the mean levels of circulating adiponectin in patients with gestational diabetes mellitus (GDM) and the association between adiponectin levels and GDM risk. Methods PubMed, EMBASE and Web of Science were searched from their inception until November 8th, 2022, for nested case-control studies and cohort studies. Random-effect models were applied to the synthesized effect sizes. The difference in circulating adiponectin levels between the GDM and control groups was measured using the pooled standardized mean difference (SMD) and 95% confidence interval (CI). The relationship between circulating adiponectin levels and GDM risk was examined using the combined odds ratio (OR) and 95% CI. Subgroup analyses were performed according to the study continent, GDM risk in the study population, study design, gestational weeks of circulating adiponectin detection, GDM diagnostic criteria, and study quality. Sensitivity and cumulative analyses were performed to evaluate the stability of the meta-analysis. Publication bias was assessed by funnel plots and Egger’s test. Results The 28 studies included 13 cohort studies and 15 nested case-control studies, containing 12,256 pregnant women in total. The mean adiponectin level in GDM patients was significantly lower than in controls (SMD = −1.514, 95% CI = −2.400 to −0.628, p = .001, I2 = 99%). The risk of GDM was significantly decreased among pregnant women with increasing levels of circulating adiponectin (OR = 0.368, 95% CI = 0.271–0.500, p < .001, I2=83%). There were no significant differences between the subgroups. Conclusions Our findings indicate that increasing circulating adiponectin levels were inversely associated with the risk of GDM. Given the inherent heterogeneity and publication bias of the included studies, further well-designed large-scale prospective cohort or intervention studies are needed to confirm our finding. KEY MESSAGES Increasing circulating adiponectin levels in the first to the second trimester could decrease the risk of incident GDM.