Miracle-dz/UniFAR-FTUs huggingface dataset:
The Glycan-Binding Trait of the Sarbecovirus Spike N-Terminal Domain Reveals an Evolutionary Footprint

Spike N-terminal domains (S-NTD) of sarbecoviruses are highly diverse; however, their function remains largely understudied compared with the receptor-binding domains (RBD). Here, we show that sarbecovirus S-NTD can be phylogenetically clustered into five clades and exhibit various levels of glycan binding in vitro. ABSTRACT The spike protein on sarbecovirus virions contains two external, protruding domains: an N-terminal domain (NTD) with unclear function and a C-terminal domain (CTD) that binds the host receptor, allowing for viral entry and infection. While the CTD is well studied for therapeutic interventions, the role of the NTD is far less well understood for many coronaviruses. Here, we demonstrate that the spike NTD from SARS-CoV-2 and other sarbecoviruses binds to unidentified glycans in vitro similarly to other members of the Coronaviridae family. We also show that these spike NTD (S-NTD) proteins adhere to Calu3 cells, a human lung cell line, although the biological relevance of this is unclear. In contrast to what has been shown for Middle East respiratory syndrome coronavirus (MERS-CoV), which attaches sialic acids during cell entry, sialic acids present on Calu3 cells inhibited sarbecovirus infection. Therefore, while sarbecoviruses can interact with cell surface glycans similarly to other coronaviruses, their reliance on glycans for entry is different from that of other respiratory coronaviruses, suggesting sarbecoviruses and MERS-CoV have adapted to different cell types, tissues, or hosts during their divergent evolution. Our findings provide important clues for further exploring the biological functions of sarbecovirus glycan binding and adds to our growing understanding of the complex forces that shape coronavirus spike evolution. IMPORTANCE Spike N-terminal domains (S-NTD) of sarbecoviruses are highly diverse; however, their function remains largely understudied compared with the receptor-binding domains (RBD). Here, we show that sarbecovirus S-NTD can be phylogenetically clustered into five clades and exhibit various levels of glycan binding in vitro. We also show that, unlike some coronaviruses, including MERS-CoV, sialic acids present on the surface of Calu3, a human lung cell culture, inhibit SARS-CoV-2 and other sarbecoviruses. These results suggest that while glycan binding might be an ancestral trait conserved across different coronavirus families, the functional outcome during infection can vary, reflecting divergent viral evolution. Our results expand our knowledge on the biological functions of the S-NTD across diverse sarbecoviruses and provide insight on the evolutionary history of coronavirus spike.
Further Dimensions for Sensing in Biofluids: Distinguishing Bioorganic Analytes by the Salt-Induced Adaptation of a Cucurbit[7]uril-Based Chemosensor

Insufficient binding selectivity of chemosensors often renders biorelevant metabolites indistinguishable by the widely used indicator displacement assay. Array-based chemosensing methods are a common workaround but require additional effort for synthesizing a chemosensor library and setting up a sensing array. Moreover, it can be very challenging to tune the inherent binding preference of macrocyclic systems such as cucurbit[n]urils (CBn) by synthetic means. Using a novel cucurbit[7]uril-dye conjugate that undergoes salt-induced adaptation, we now succeeded in distinguishing 14 bioorganic analytes from each other through the facile stepwise addition of salts. The salt-specific concentration-resolved emission provides additional information about the system at a low synthetic effort. We present a data-driven approach to translate the human-visible curve differences into intuitive pairwise difference measures. Ion mobility experiments combined with density functional theory calculations gave further insights into the binding mechanism and uncovered an unprecedented ternary complex geometry for CB7. TThis work introduces the non-selectively binding, salt-adaptive cucurbit[n]uril system for sensing applications in biofluids such as urine, saliva, and blood serum.
The influence of food environments on dietary behaviour and nutrition in Southeast Asia: A systematic scoping review

Background: Food environments are crucial spaces within the food system for understanding and addressing many of the shared drivers of malnutrition. In recent years, food environment research has grown rapidly, however, definitions, measures, and methods remain highly inconsistent, leading to a body of literature that is notably heterogeneous and poorly understood, particularly within regions of the Asia-Pacific. Aim: This scoping review aims to synthesize the nature, extent, and range of published literature surrounding the role of the food environment on influencing dietary behaviour and nutrition in Southeast Asia. Methods: A systematic search of 5 databases was conducted following PRISMA guidelines for scoping reviews. Eligible studies included peer-reviewed research with adult participants living in Southeast Asia that examined the food environment as a determinant of dietary behaviour or nutrition. Results: A total of 45 articles were included. Overall, studies indicated that dietary behaviours in Southeast Asia were primarily driven by social, cultural, and economic factors rather than physical (e.g. geographical) features of food environments. Food price and affordability were most consistently identified as key barriers to achieving healthy diets. Conclusion: This work contributes to the establishment of more robust conceptualizations of food environments within diverse settings which may aid future policymakers and researchers identify and address the barriers or obstacles impacting nutrition and food security in their communities. Further research is needed to strengthen this knowledge, particularly research that explicitly explores the macro-level mechanisms and pathways that influence diet and nutrition outcomes.
Insulin Resistance and Cognitive Impairment: Evidence From Neuroimaging

Insulin is a peptide well known for its role in regulating glucose metabolism in peripheral tissues. Emerging evidence from human and animal studies indicate the multifactorial role of insulin in the brain, such as neuronal and glial metabolism, glucose regulation, and cognitive processes. Insulin resistance (IR), defined as reduced sensitivity to the action of insulin, has been consistently proposed as an important risk factor for developing neurodegeneration and cognitive impairment. Although the exact mechanism of IR‐related cognitive impairment still awaits further elucidation, neuroimaging offers a versatile set of novel contrasts to reveal the subtle cerebral abnormalities in IR. These imaging contrasts, including but not limited to brain volume, white matter (WM) microstructure, neural function and brain metabolism, are expected to unravel the nature of the link between IR, cognitive decline, and brain abnormalities, and their changes over time. This review summarizes the current neuroimaging studies with multiparametric techniques, focusing on the cerebral abnormalities related to IR and therapeutic effects of IR‐targeting treatments. According to the results, brain regions associated with IR pathophysiology include the medial temporal lobe, hippocampus, prefrontal lobe, cingulate cortex, precuneus, occipital lobe, and the WM tracts across the globe. Of these, alterations in the temporal lobe are highly reproducible across different imaging modalities. These structures have been known to be vulnerable to Alzheimer's disease (AD) pathology and are critical in cognitive processes such as memory and executive functioning. Comparing to asymptomatic subjects, results are more mixed in patients with metabolic disorders such as type 2 diabetes and obesity, which might be attributed to a multifactorial mechanism. Taken together, neuroimaging, especially MRI, is beneficial to reveal early abnormalities in cerebral structure and function in insulin‐resistant brain, providing important evidence to unravel the underlying neuronal substrate that reflects the cognitive decline in IR.
Sexual stature difference fluctuations in pre‐ and post‐Black Death London as an indicator of living standards

The degree of sexual stature difference (SSD), the ratio of male to female height, is argued to be an indicator of living standards based on evidence that physical growth for males is more sensitive to environmental fluctuations. In a resource‐poor environment, the degree of SSD is expected to be relatively low. The aim of this study is to comparatively assess SSD in medieval London in the context of repeated famine events and other environmental stressors before the Black Death (BD) and the improved living conditions that characterized the post‐Black Death period.
Fast generation of planar graphs

The program plantri is the fastest isomorph-free generator of many classes of planar graphs, including triangulations, quadrangulations, and convex polytopes. Many applications in the natural sciences as well as in mathematics have appeared. This paper describes plantri's principles of operation, the basis for its efficiency, and the recursive algorithms behind many of its capabilities. In addition, we give many counts of isomorphism classes of planar graphs compiled using plantri. These include triangulations, quadrangulations, convex polytopes, several classes of cubic and quartic graphs, and triangulations of disks.
Intimate partner violence and the situation of women experiencing intimate partner violence during the COVID‐19 pandemic: A qualitative study of Japanese clinician views

Abstract Aim Intimate partner violence (IPV) is a major global threat to women's health. Stay‐at‐home orders during the coronavirus disease 2019 (COVID‐19) pandemic were associated with an increase in IPV. The purpose of this study was to clarify IPV and the situation of women experiencing IPV during the COVID‐19 pandemic in Japan. Methods A semi‐structured interview was conducted with five healthcare providers who gave support to women experiencing IPV during the COVID‐19 pandemic. All interviews were audio‐recorded, transcribed and analyzed in accordance with thematic analysis methodology. Results Two categories concerning IPV and the situation of women experiencing IPV during the COVID‐19 pandemic emerged from analysis of interviews: (1) the possibility that IPV might change during the pandemic; and (2) barriers that prevent women getting support. “Possibility that IPV might change during the pandemic” consisted of three subcategories: “Male partner takes his stress out on her”; “Male partner forced her out of the home”; and “Conflict occurred more easily at home”. “Barriers that prevent women getting support” had four subcategories: “Difficulty in accessing outside support”; “Restricted access to get care due to financial difficulties”; “Lack of support from her family”; and “Women experience a loss of energy”. Conclusions During the COVID‐19 pandemic, there were barriers to provide support for women despite increased IPV. Healthcare providers should support women using effective methods to protect women's health and safety.
Women’s experiences of a pregnancy whilst attending a specialist antenatal service for pregnancies after stillbirth or neonatal death: a qualitative interview study

Abstract Aim: Pregnancy after the death of a baby is associated with numerous, varied psychological challenges for pregnant women. This study aimed to explore women’s experiences of pregnancy whilst attending a specialist antenatal service for pregnancies after a perinatal death. Methods: Semi-structured interviews with twenty women in a subsequent pregnancy after a perinatal death were conducted and analyzed taking an inductive thematic analysis approach. Results: All women expressed a heightened “awareness of risk”. Two subthemes demonstrated how increased awareness of risk affected their experience and their desire regarding antenatal and postnatal support. Women talked about stillbirth being a “quiet, unspoken subject” causing them internal conflict as they had an awareness of pregnancy complications that other people did not. Navigating subsequent pregnancies relied on them “expecting the worst and hoping for the best” in terms of pregnancy outcomes. Women viewed specialist antenatal care in pregnancy after perinatal loss favorably, as it enabled them to receive tailored care that met their needs stemming from their increased awareness of and personal expectations of risk. Conclusion: Women’s experiences can be used to develop models of care but further studies are required to determine to identify which components are most valued.
Lipid Transport Across Bacterial Membranes.

The movement of lipids within and between membranes in bacteria is essential for building and maintaining the bacterial cell envelope. Moving lipids to their final destination is often energetically unfavorable and does not readily occur spontaneously. Bacteria have evolved several protein-mediated transport systems that bind specific lipid substrates and catalyze the transport of lipids across membranes and from one membrane to another. Specific protein flippases act in translocating lipids across the plasma membrane, overcoming the obstacle of moving relatively large and chemically diverse lipids between leaflets of the bilayer. Active transporters found in double-membraned bacteria have evolved sophisticated mechanisms to traffic lipids between the two membranes, including assembling to form large, multiprotein complexes that resemble bridges, shuttles, and tunnels, shielding lipids from the hydrophilic environment of the periplasm during transport. In this review, we explore our current understanding of the mechanisms thought to drive bacterial lipid transport. Expected final online publication date for the Annual Review of Cell and Developmental Biology Volume 38 is October 2022. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
NR1H3 (LXRα) is associated with pro‐inflammatory macrophages, predicts survival and suggests potential therapeutic rationales in diffuse large b‐cell lymphoma

The role of macrophages (Mo) and their prognostic impact in diffuse large B‐cell lymphomas (DLBCL) remain controversial. By regulating the lipid metabolism, Liver‐X‐Receptors (LXRs) control Mo polarization/inflammatory response, and their pharmacological modulation is under clinical investigation to treat human cancers, including lymphomas. Herein, we surveyed the role of LXRs in DLBCL for prognostic purposes. Comparing bulk tumors with purified malignant and normal B‐cells, we found an intriguing association of NR1H3, encoding for the LXR‐α isoform, with the tumor microenvironment (TME). CIBERSORTx‐based purification on large DLBCL datasets revealed a high expression of the receptor transcript in M1‐like pro‐inflammatory Mo. By determining an expression cut‐off of NR1H3, we used digital measurement to validate its prognostic capacity on two large independent on‐trial and real‐world cohorts. Independently of classical prognosticators, NR1H3high patients displayed longer survival compared with NR1H3low cases and a high‐resolution Mo GEP dissection suggested a remarkable transcriptional divergence between subgroups. Overall, our findings indicate NR1H3 as a Mo‐related biomarker identifying patients at higher risk and prompt future preclinical studies investigating its mouldability for therapeutic purposes.
PIWI‐interacting RNAs and human testicular function

Abstract Small noncoding RNAs (sncRNAs) are pieces of RNA with a length below 200 bp and represent a diverse group of RNAs having many different biological functions. The best described subtype is the microRNAs which primarily function in posttranscriptional gene regulation and appear essential for most physiological processes. Of particular interest for the germline is the PIWI‐interacting RNAs (piRNAs) which are a class of sncRNA of 21–35 bp in length that are almost exclusively found in germ cells. Recently, it has become clear that piRNAs are essential for testicular function, and in this perspective, we outline the current knowledge of piRNAs in humans. Although piRNAs appear unique to germ cells, they have also been described in various somatic cancers and biofluids. Here, we discuss the potential function of piRNAs in somatic tissues and whether detection in biofluids may be used as a biomarker for testicular function. This article is categorized under: Reproductive System Diseases > Genetics/Genomics/Epigenetics Reproductive System Diseases > Molecular and Cellular Physiology
Fatigue and quality of life in patients with neuroendocrine neoplasia

Abstract Introduction Neuroendocrine Neoplasms (NEN) are rare tumours arising in the gastro-intestinal tract or lungs. Poor health related quality of life (HRQoL) is associated with the carcinoid syndrome (CS), but fatigue is also important. We aimed to quantify HRQoL and fatigue in out-patients with NEN. Methods In a cross-sectional study, we included 231 patients with NEN (G1-G3). We used pre-validated questionnaires MFI-20, EQ-5D-5L and 85% responded. We collected clinical, biochemical, imaging, and pathology data from Electronic Patient files. Normative values for fatigue and HRQoL were derived from background populations. Results Median age was 68 years (range 21–91) and 52% were male. Patients with NEN reported more fatigue and worse HRQoL compared to the background population (p < .05). Cured patients reported higher HRQoL than patients with current disease, and patients with high grade neoplasms (G2–G3) reported more anxiety and depression compared to patients with low grade G1 disease (p < .05). The CS resulted in a 9% relative loss in Quality Adjusted Life Years compared to patients without CS. (p < .05). More than 50% of patients with CS reported problems with usual activities, pain/discomfort, and anxiety/depression. Overall, 36% of patients with NEN were fatigued and 92% of these had psychological fatigue. Younger patients (<65 years) experienced more fatigue than older patients (p < .05). Conclusion Patients with NEN report significantly lower HRQoL and more fatigue compared to the background population. Especially, patients with CS had pain, discomfort, anxiety, and depression and a relative reduction in HRQoL. However, compared to other cancer types, patients with NEN experience less fatigue.
Application and modification of bone cement in vertebroplasty: A literature review

Vertebral compression fractures are more common in the elderly, particularly in postmenopausal women. Most of these people are accompanied by osteoporosis, which can easily lead to spinal deformities and fractures. Once a fracture occurs, the patient would have severe pain response, limited spinal movement, and need to stay in bed for a long time, resulting in a significant decrease in their quality of life. Percutaneous vertebroplasty (PVP) is a minimally invasive spinal surgery that injects bone cement into the diseased vertebrae for therapeutic purposes. It can quickly relieve pain and stabilize the spine. It is widely used in the treatment of vertebral compression fractures and is currently an ideal treatment method. There are many materials of bone cement used in clinical treatment, and each material has unique characteristics. Many scholars would modify the bone cement according to the advantages and disadvantages to make it more suitable for clinical use. In this review, we discuss the clinical application and modification of bone cement.
Ambivalence experienced by infertile couples undergoing IVF: a qualitative study

Abstract The emotional consequences of infertility are well documented. However, relatively few studies have emphasized the dyadic emotional interaction within couples, despite infertility being a shared life event. This study adopted a dyadic (between two people) approach to explore the emotional complexity that infertile couples face. A descriptive qualitative study was conducted with 24 participants, including eight infertile couples and eight wives undergoing infertility treatments. Conjoint and individual interviews were conducted through purposive sampling in a large fertility centre in Tianjin, China, between June and August 2015. Thematic analysis identified two main themes: (i) ‘decisional ambivalence’, with subthemes of ‘ambivalent attitudes towards treatment’, ‘uncertainty about treatment outcomes’, and ‘treatment-related lifestyle changes’; and (ii) ‘relational ambivalence’ which included subthemes of ‘intergenerational ambivalence’ and ‘partner ambivalence’. Complex emotions of ambivalence among infertile couples were common as infertility clearly shattered their assumptive world on family formation. With complex entanglement of mixed emotions, ambivalence was intimately associated with cultural norms, social expectations, and active or over engagement of family members in Chinese societies. Since ambivalence could threaten mental and physical health during pregnancy, healthcare professionals should be prepared to assist infertile couples with identifying, articulating, and normalizing decisional and relational ambivalence during the treatment process.
Defer no more: advances in the treatment and prevention of chronic hepatitis C virus infection in children

Purpose of review Direct-acting antiviral (DAA) regimens targeting hepatitis C virus (HCV) are now approved for young children. This review examines recent DAA experience in children, current treatment recommendations and challenges, and potential treatment-as-prevention strategies. Recent findings In 2021, the US FDA extended approval of two pan-genotypic DAA regimens, glecaprevir/pibrentasvir and sofosbuvir/velpatasvir, to children as young as age 3 years based on high success rates and reassuring safety profiles in registry trials. Similar performance has been replicated with real-world DAA use in thousands of adolescents and in limited reports of children with high-risk conditions, including cirrhosis, cancer, thalassemia and HIV-coinfection. Treatment without delay is now recommended in the USA for viremic children aged 3 years and up to prevent disease progression and future spread. To date, treatment expansion is limited by high rates of undiagnosed paediatric infection. Universal prenatal screening will aid identification of perinatally exposed newborns, but new strategies are needed to boost testing of exposed infants and at-risk adolescents. Postpartum treatment programmes can prevent subsequent vertical transmission but are hampered by low rates of linkage to care and treatment completion. These challenges may be avoided by DAA use in pregnancy, and this warrants continued study. Summary Paediatric HCV is now readily curable. Substantial clinical and public health effort is required to ensure widespread uptake of this therapeutic breakthrough.
Supplemental Materials: GA-MADRID: Design and validation of a machine learning tool for the diagnosis of neugodegenerative disorders using genetic algorithms

This supplementary material contains information about the structure of the database designed for the proposed framework. The MySQL database schema is shown in the main document, and Figure 1 details the number of features in each table, the type of data and its description. Tables brodmann qualitative / quantitative and aal qualitative / quantitative, corresponding to the brain metabolism. References Bitam and Mellouk (2006); Tzourio-Mazoyer et al. (2002) presented the two different atlases considered in this framework, the Brodmann’s atlas (47 regions) and the Automated Anatomical Labelling (AAL) atlas (90 regions), respectively.