Miracle-dz/UniFAR-FTUs huggingface dataset:
Magnitude and Associated Factors of Suicidal Ideation Among Cancer Patients at Ayder Comprehensive Specialized Hospital, Mekelle, Ethiopia, 2019: Cross-sectional Study

Background Suicide is a worldwide public health issue and considered as a psychiatric emergency. The majority of all completed suicides occur in low- and middle-income countries. A diagnosis of cancer has been associated with an increased risk of suicidal ideation and suicide is one of the leading causes of non-cancer-related mortality among cancer patients in recent years. Suicidal ideation is four times higher in cancer patients than in the general population. There is limited evidence on suicidal ideation on patients diagnosed with cancer in Ethiopia as well as in African countries. Objective To assess the magnitude and associated factors of suicide ideation among cancer patients at Ayder Comprehensive Specialized Hospital, Mekelle, Ethiopia, 2019. Methods An institution-based cross-sectional study was conducted from May 1 to 30, 2019. Systematic random sampling technique was used and a total of 410 of cancer patients participated in the study. Data were collected using the Suicide Manual of Composite International Diagnostic Interview (CIDI) questionnaire. Data were coded, entered into EpiData manager version 4.4 and analyzed using SPSS version 20. Descriptive, analytical statistical procedures, bivariable, multivariable logistic regression with odds ratio, 95% confidence interval were employed. The statistical significance was declared at P-value <0.05. Results The finding of the present study on magnitude of suicidal ideation among cancer patients were 28.5% with 95%CI: 24.1–33.2, respectively. In multivariable logistic regression analysis being female advanced stage, perceived stigma and anxiety was significantly associated with suicidal ideation. Conclusion and Recommendation The magnitude of suicidal ideation among cancer patients was higher than in the general population. It also reported that, advanced stage, perceived stigma, anxiety and being female were factors significantly associated with suicidal ideation. This study gives us clues that cancer patients are prone to suicide ideation. Therefore, cancer patients need special attention to reduce these problems.
Marital Experiences and Depression in an Arranged Marriage Setting1

Understanding the consequences of marital experiences for individual mental health provides insight into how social relationships shape individual well-being. Using newly available, clinically validated diagnostic interviews with more than 10,000 respondents, the authors assess the associations between marital experiences, intimate partner violence (IPV), and mental health, investigating how they differ by gender in a setting of universal marriage. Integrating measures of arranged marriage, IPV, and marital quality into a single comprehensive analysis of the marital experiences reveals that becoming married can be positively associated with subsequent major depressive disorder for women. IPV is a strong and independent risk factor for depression, but it only mediates a small portion of the consequences of marriage and arranged marriage on depression. The authors also investigate the associations between the positive and negative dimensions of marital quality and depression. Overall, the associations between marital experiences and mental health should be understood as contingent on both gender and the social contexts of marriage. Depending on these factors, specific marital experiences have the potential to increase transitions to depression.
Brief exposure to warm temperatures reduces intron retention in Kdm6b in a species with temperature-dependent sex determination

Animals with temperature-dependent sex determination (TSD) respond to thermal cues during early embryonic development to trigger gonadal differentiation. TSD has primarily been studied using constant temperature incubations, where embryos are exposed to constant male- or female-producing temperatures, and these studies have identified genes that display sex-specific expression in response to incubation temperature. Kdm6b, a histone demethylase gene, has received specific attention as it is among the initial genes to respond to incubation temperature and is necessary for testis development. Interestingly, Kdm6b retains an intron when eggs are incubated at a constant male-producing temperature, but the role of thermal variability in this developmental process is relatively understudied. Species with TSD regularly experience thermal cues that fluctuate between male- and female-producing temperatures throughout development but it is unclear how Kdm6b responds to such variable temperatures. In this study, we investigate temperature-sensitive splicing in Kdm6b by exposing embryos to male- and female-producing thermal conditions. We show a rapid decrease in levels of the intron retaining transcript of Kdm6b upon exposure to female-producing conditions. These results demonstrate that, under ecologically relevant conditions, temperature-sensitive splicing can differentially regulate genes critical to TSD.
The avian compass can be sensitive even without sustained electron spin coherence

Theoretical studies indicating the presence of long-lived coherence in the radical pair system have engendered questions about its utilitarian role in the avian compass. In this paper, we investigate the role of electron spin coherence in a multinuclear radical pair system including its impact on compass sensitivity. We find that sustenance of long-lived electron spin coherence is unlikely in a multinuclear hyperfine environment. After probing the role of the hyperfine interactions in the compass, we affirm the hyperfine anisotropy to be an essential parameter for the necessary sensitivity required for the compass action. Thereby, we identify a parameter regime where the compass would exhibit good sensitivity even without sustained electron spin coherence.
Adaptive, caste-specific changes to recombination rates in a thelytokous honeybee population

The ability to clone oneself has clear benefits—no need for mate hunting or dilution of one's genome in offspring. It is therefore unsurprising that some populations of haplo-diploid social insects have evolved thelytokous parthenogenesis—the virgin birth of a female. But thelytokous parthenogenesis has a downside: the loss of heterozygosity (LoH) as a consequence of genetic recombination. LoH in haplo-diploid insects can be highly deleterious because female sex determination often relies on heterozygosity at sex-determining loci. The two female castes of the Cape honeybee, Apis mellifera capensis, differ in their mode of reproduction. While workers always reproduce thelytokously, queens always mate and reproduce sexually. For workers, it is important to reduce the frequency of recombination so as to not produce offspring that are homozygous. Here, we ask whether recombination rates differ between Cape workers and Cape queens that we experimentally manipulated to reproduce thelytokously. We tested our hypothesis that Cape workers have evolved mechanisms that restrain genetic recombination, whereas queens have no need for such mechanisms because they reproduce sexually. Using a combination of microsatellite genotyping and whole-genome sequencing we find that a reduction in recombination is confined to workers only.
The three-component helicase/primase complex of herpes simplex virus-1

Herpes simplex virus type 1 (HSV-1) is one of the nine herpesviruses that infect humans. HSV-1 encodes seven proteins to replicate its genome in the hijacked human cell. Among these are the herpes virus DNA helicase and primase that are essential components of its replication machinery. In the HSV-1 replisome, the helicase–primase complex is composed of three components including UL5 (helicase), UL52 (primase) and UL8 (non-catalytic subunit). UL5 and UL52 subunits are functionally interdependent, and the UL8 component is required for the coordination of UL5 and UL52 activities proceeding in opposite directions with respect to the viral replication fork. Anti-viral compounds currently under development target the functions of UL5 and UL52. Here, we review the structural and functional properties of the UL5/UL8/UL52 complex and highlight the gaps in knowledge to be filled to facilitate molecular characterization of the structure and function of the helicase–primase complex for development of alternative anti-viral treatments.
Intensive human contact correlates with smaller brains: differential brain size reduction in cattle types

Cattle are one of the most intensively bred domestic animals, providing humans with a multitude of products and uses. Using data from the fossil record, we test if their domestication, as for other taxa, has resulted in a reduction of their brain size. We not only conclude that Bos taurus (domestic cattle) have smaller brains than their wild ancestor, Bos primigenius (aurochs), but that brain size varies significantly by breed, with some having much smaller brains than others. Differences in husbandry practices between several breed categories align with a range of human engagement, which also aligns with the degree of selection for docility. Sampling 317 domestics from 71 breeds, we investigate if differences in brain size correlate with the intensity of human contact. A clear pattern emerges whereby a brain reduction gradient parallels a gradient in behavioural selection. Bullfighting cattle, which are bred for fighting and aggressive temperament, have much larger brains than dairy breeds, which are intensively selected for docility. Our results add to a fundamental aspect of animal domestication theory: the interplay between basic features of the domestic environment—selection for docility, absence of predators and human provision of resources—seems to explain differences in brain size.
Kindlin-3 disrupts an intersubunit association in the integrin LFA1 to trigger positive feedback activation by Rap1 and talin1

Kindlin-3 stimulates ligand-induced activation of the integrin LFA1 by promoting a high-affinity conformation. Linking inside-out and outside-in signaling Integrins link the cytoskeleton to the extracellular matrix and mediate both outside-in signaling, which transduces cellular responses to ligands, and inside-out signaling, which controls ligand affinity. Talins and kindlins associate with the intracellular domains of integrins and coordinate bidirectional signaling. Using single-molecule imaging of lymphocytes, Kondo et al. found that ligand binding to the integrin LFA1 induced transient interactions with talin1, which recruited kindlin-3, led to a conformational change in LFA1, and stabilized talin1 binding. These effects stimulated the inside-out signaling mediator Rap1, causing LFA1 to adopt an open, high-affinity conformation. In migrating lymphocytes, the association of talin1 and kindlin-3 with LFA1 corresponded to LFA1 adopting the high-affinity conformation in the body of the cell but remaining in a low-affinity conformation at the leading edge. Thus, kindlin-3 mediates positive feedback in the ligand-induced conversion of LFA1 from a low-affinity conformation to a high-affinity conformation. Integrin activation by the intracellular adaptor proteins talin1 and kindlin-3 is essential for lymphocyte adhesion. These adaptors cooperatively control integrin activation through bidirectional (inside-out and outside-in) activation signals. Using single-molecule measurements, we revealed the distinct dynamics of talin1 and kindlin-3 interactions with the integrin LFA1 (αLβ2) and their functions in LFA1 activation and LFA1-mediated adhesion. The kinetics of talin1 binding to the tail of the β2 subunit corresponded to those of LFA1 binding to its ligand ICAM1. ICAM1 binding induced transient interactions between the membrane-proximal cytoplasmic region of the β2 subunit with an N-terminal domain of kindlin-3, leading to disruption of the association between the integrin subunits (the α/β clasp) and unbending of the ectodomains of the α/β heterodimer. These conformational changes promoted high-affinity talin1 binding to the β2 tail that required the talin rod domain and the actomyosin cytoskeleton. Inside-out signaling induced by the GTPase Rap1 did not markedly stabilize the binding of talin1 and kindlin-3 to LFA1. In contrast, ligand-induced outside-in signaling, the stabilization of open LFA1 conformers, or shear force substantially altered the dynamics of talin1 and kindlin-3 association with LFA1 and enhanced both Rap1 and LFA1 activation. In migrating lymphocytes, asymmetrical distribution of talin1 and kindlin-3 correlated with the maturation of LFA1 from a low-affinity conformation at the leading edge to a high-affinity conformation in the adherent mid-body. Our results suggest that kindlin-3 spatiotemporally mediates a positive feedback circuit of LFA1 activation to control dynamic adhesion and migration of lymphocytes.
Factors influencing complementary feeding practices in rural and semi-urban Rwanda: a qualitative study

Abstract The aim of the present study was to identify and describe the factors influencing feeding practices of children aged 6–23 months in Rwanda. This is a cross-sectional descriptive qualitative study. A total of ten focus group discussions were conducted separately with mothers, fathers, grandmothers and community health workers (CHWs) from five different districts in Rwanda. The discussions were recorded, transcribed verbatim, and thematically analysed using qualitative data analysis software, Atlas.ti. The study participants were mothers, fathers and grandmothers of children aged 6–23 months and CHWs in charge of child health. Caregivers’ knowledge and beliefs about the benefits of breast-feeding and timely introduction of complementary food were found to be the primary individual factors facilitating good infant and young child feeding practices. The common belief of caregivers that infants should be given liquids (thin gruel, fruit juices and meat broth) as first foods instead of semi-solid foods was a barrier to good feeding practices. The community-based nutrition education and counselling programmes were facilitators of good complementary practices at the group level. At the society level, poverty in rural agrarian households was a barrier to optimal feeding practices. The study shows that there is a need to empower caregivers with more specific guidelines, especially on complementary feeding.
High‐risk follicular lymphoma: Treatment options

Follicular lymphoma (FL) is the most common indolent non‐Hodgkin lymphoma in the Western hemisphere. The natural history of FL appears to have been favorably impacted by the introduction of rituximab. Randomized clinical trials have demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival. Maintenance rituximab strategies can improve progression‐free survival (PFS). Obinutuzumab was superior to rituximab for PFS in the GALLIUM study, although the benefit was small and required more drug. Chemotherapy platforms have changed in the past decade, as bendamustine combined with rituximab has become commonly utilized frontline strategy in North America and parts of Europe, although there is certainly no one standard treatment. However, several unmet needs remain, including a better ability to identify high‐risk patients at diagnosis, the development of predictive biomarkers for targeted agents, the development of novel combinations, and strategies to reduce the risk of transformation. A multitude of novel therapies are under investigation in both the frontline and relapsed/refractory settings. It will be critical to identify the most appropriate populations for new agents and to develop validated surrogate endpoints, so that novel agents can be tested (and adopted, if appropriate) efficiently.
Personalized medicine for Hodgkin lymphoma: Mitigating toxicity while preserving cure

The treatment of classical Hodgkin lymphoma in young patients is one of the success stories of modern medicine. The use of risk‐ and response‐adapted approaches to guide treatment decisions has led to impressive cure rates while reducing the long‐term toxicity associated with more intensive therapies. Tissue biomarkers have not yet proven more effective than clinical characteristics for risk stratification of patients at presentation, but functional imaging features such as metabolic tumor volume may be used to predict response, if early observations can be validated. The success of treatment in younger patients has unfortunately not been mirrored in those over 60, where complex decision‐making is often required, with a paucity of data from clinical trials. The use of PD1 blocking antibodies and brentuximab vedotin in this cohort, either alone or in combination with chemotherapy, may provide attractive options. The incorporation of frailty assessment, quality‐of‐life outcomes, and specialist geriatric input is also important to ensure the best outcomes for this diverse group.
Current and future state of clinical pharmacist‐led precision medicine initiatives

This white paper evaluates the current and future state of clinical pharmacist‐led precision medicine initiatives, focusing on an overview of pharmacogenomics (PGx) in three key areas: clinical practice, education, and research. These key facets are described in detail, followed by a review of potential and perceived barriers concerning PGx and recommendations for the clinical pharmacist's role in overcoming these barriers. This paper reviews the current state of clinical pharmacist‐led precision medicine and presents a vision for the future of pharmacy practice in this quickly evolving field.
Allogeneic stem cell transplant in non‐Hodgkin lymphomas: Still an indication?

Allogeneic hematopoietic cell transplantation (alloHCT) used to play a defined role in the treatment of non‐Hodgkin lymphoma (NHL). With the advent of modern targeted molecular therapies and immunotherapies, treatment standards at least for B‐cell lymphoma have undergone significant changes, thereby questioning the traditional role of alloHCT in these diseases. This paper attempts to describe the current place and the perspectives of alloHCT in the rapidly evolving treatment landscape of NHL.
What's new in peripheral T‐cell lymphomas

Peripheral T‐cell lymphomas (PTCLs) are a rare, heterogeneous group of hematological malignancies with extremely poor prognosis for almost all subtypes. The diverse clinicopathological features of PTCLs make accurate diagnosis, prognosis, and choice of optimal treatment strategies difficult. Moreover, the best therapeutic algorithms are still under debate due to the extrapolated approaches developed for B‐cell lymphomas and to the absence of few treatment protocol specifically developed for PTCLs. Some advances have been made with CD30 monoclonal antibody, mainly for anaplastic large‐cell lymphomas, with improvements in progression‐free survival and overall survival. Several new drugs are under evaluation in clinical trials, although not all the results are as encouraging as expected. In this review, we briefly present the most updated information on diagnosis, prognostication, and treatment strategies in PTCLs.
A marginal habitat, but not a sink: Ecological genetics reveal a diversification hotspot for marine invertebrates in the brackish Baltic Sea

Aim Environmental gradients have emerged as important barriers structuring populations and species distributions. We set out to test whether a strong salinity gradient from marine to brackish, represented in a marginal northern European sea, should be considered a diversification hotspot or a population sink, and to identify life history traits that correlate with either evolutionary trajectory. Location The Baltic Sea, the North Sea and their transition zone. Methods We accumulated mitochondrial cytochrome oxidase subunit 1 sequence data and data on the distribution, salinity tolerance and life history for 28 species belonging to the Cnidaria, Crustacea, Echinodermata, Mollusca, Polychaeta and Gastrotricha, including seven non-native species. We calculated measures of genetic diversity and differentiation across the environmental gradient, coalescent times and migration rates between North and Baltic Sea populations, and analysed correlations between genetic and life history data. Results The majority of investigated species is either genetically differentiated and/or is adapted to the lower salinity conditions of the Baltic Sea. Moreover, the species exhibiting population structure have a range of patterns of genetic diversity in comparison to the North Sea, from lower in the Baltic Sea to higher in the Baltic Sea, or equally diverse in North and Baltic Sea. Main conclusions Our results indicate that the Baltic Sea should be considered a diversification hotspot: The diversity of genetic patterns points towards independent trajectories in the Baltic compared to the North Sea. At the same time, we found limited evidence for the traditional scenario of the Baltic Sea as a population sink with lower diversity and strong gene flow. The North Sea - Baltic Sea region provides a unique setting to study evolutionary adaptation during colonization processes at different stages by jointly considering native and non-native species.
Single-cell RNA-sequencing reveals widespread personalized, context-specific gene expression regulation in immune cells

Gene expression and its regulation can be context-dependent. To dissect this, using samples from 120 individuals, we single-cell RNA-sequenced 1.3M peripheral blood mononuclear cells exposed to three different pathogens at two time points or left unexposed. This revealed thousands of cell type-specific expression changes (eQTLs) and pathogen-induced expression changes (response QTLs) that are influenced by genetic variation. In monocytes, the strongest responder to pathogen stimulations, genetics also affected co-expression of 71.4% of these eQTL genes. For example, the pathogen recognition receptor CLEC12A showed many such co-expression interactions, but only in monocytes after 3h pathogen stimulation. Further analysis linked this to interferon-regulating transcription factors, a finding that we recapitulated in an independent cohort of patients with systemic lupus erythematosus, a condition characterized by increased interferon activity. Altogether, this study highlights the importance of context for gaining a better understanding of the mechanisms of gene regulation in health and disease.