Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular causes of an evolutionary shift along the parasitism–mutualism continuum in a bacterial symbiont

Significance Symbiotic relationships with microbes are ubiquitous among living beings and can be parasitic, such as in bacterial pathogens, or mutualistic, as in beneficial microbiomes. Among other factors, the outcome of microbe–host relationships is determined by the mode of symbiont transmission from host to host. Here we describe how bacterial symbionts increased in infectivity and virulence toward their amoeba host when transmission to a new host was essential for survival. The enhanced parasitism is a result of genomic changes and a pronounced switch of gene expression altering the symbionts’ mechanisms for host interaction. Our study provides both a molecular explanation as well as a blueprint for how changes in gene expression are sufficient to confer enhanced parasitism in microbes. Symbiosis with microbes is a ubiquitous phenomenon with a massive impact on all living organisms, shaping the world around us today. Theoretical and experimental studies show that vertical transmission of symbionts leads to the evolution of mutualistic traits, whereas horizontal transmission facilitates the emergence of parasitic features. However, these studies focused on phenotypic data, and we know little about underlying molecular changes at the genomic level. Here, we combined an experimental evolution approach with infection assays, genome resequencing, and global gene expression analysis to study the effect of transmission mode on an obligate intracellular bacterial symbiont. We show that a dramatic shift in the frequency of genetic variants, coupled with major changes in gene expression, allow the symbiont to alter its position in the parasitism–mutualism continuum depending on the mode of between-host transmission. We found that increased parasitism in horizontally transmitted chlamydiae residing in amoebae was a result of processes occurring at the infectious stage of the symbiont’s developmental cycle. Specifically, genes involved in energy production required for extracellular survival and the type III secretion system—the symbiont’s primary virulence mechanism—were significantly up-regulated. Our results identify the genomic and transcriptional dynamics sufficient to favor parasitic or mutualistic strategies.
Physician–patient racial concordance and disparities in birthing mortality for newborns

Significance A large body of work highlights disparities in survival rates across Black and White newborns during childbirth. We posit that these differences may be ameliorated by racial concordance between the physician and newborn patient. Findings suggest that when Black newborns are cared for by Black physicians, the mortality penalty they suffer, as compared with White infants, is halved. Strikingly, these effects appear to manifest more strongly in more complicated cases, and when hospitals deliver more Black newborns. No such concordance effect is found among birthing mothers. Recent work has emphasized the benefits of patient–physician concordance on clinical care outcomes for underrepresented minorities, arguing it can ameliorate outgroup biases, boost communication, and increase trust. We explore concordance in a setting where racial disparities are particularly severe: childbirth. In the United States, Black newborns die at three times the rate of White newborns. Results examining 1.8 million hospital births in the state of Florida between 1992 and 2015 suggest that newborn–physician racial concordance is associated with a significant improvement in mortality for Black infants. Results further suggest that these benefits manifest during more challenging births and in hospitals that deliver more Black babies. We find no significant improvement in maternal mortality when birthing mothers share race with their physician.
Reference Values for Pulmonary Single-Breath Diffusing Capacity – Results of the “Study of Health in Pomerania”

Abstract Objectives The assessment of pulmonary single-breath diffusing capacity is a frequently performed diagnostic procedure and considered as an important tool in medical surveillance examinations of pulmonary diseases. The aim of this study was to establish reference equations for pulmonary single-breath diffusing capacity parameters in a representative adult-population across a wide age range and to compare the normative values from this sample with previous ones. Methods Diffusing capacity measurement was carried out in 3566 participants (1811 males) of a cross-sectional, population-based survey (“Study of Health in Pomerania – SHIP”). Results Individuals with cardiopulmonary disorders and current smoking habits were excluded, resulting in 1786 healthy individuals (923 males), aged 20 – 84 years. Prediction equations for both sexes were established by quantile regression analyses, taking into consideration the influence of age, height, weight and former smoking. Conclusion The study provides a novel set of prediction equations for pulmonary single-breath diffusing capacity in an adult Caucasian population. The results are comparable to previously reported equations, underline their importance and draw attention to the need for up-to-date reference equations that adequately take into account both the subjects’ origin, age, anthropometric characteristics and the equipment used.
Assessment of Bone Lesions with 18F-FDG PET Compared with 99mTc Bone Scintigraphy Leads to Clinically Relevant Differences in Metastatic Breast Cancer Management

It is unknown whether assessment of potential bone lesions in metastatic breast cancer (MBC) by 18F-FDG PET instead of 99mTc bone scintigraphy (BS) supports clinically relevant changes in MBC management. Therefore, we retrospectively compared management recommendations based on bone lesion assessment by 18F-FDG PET plus contrast-enhanced CT (ceCT) or BS plus ceCT, for patients with newly diagnosed MBC. Methods: Baseline ceCT, BS, and 18F-FDG PET for all patients included in the IMPACT-MBC study (NCT01957332) at the University Medical Center Groningen were reviewed for bone lesions. If bone lesions were found by any imaging modality, virtual MBC management recommendations were made by a multidisciplinary expert panel, based on either 18F-FDG PET plus ceCT or BS plus ceCT. The panel had access to standard clinicopathologic information and baseline imaging findings outside the skeleton. Clinically relevant management differences between the 2 recommendations were defined either as different treatment intent (curative, noncurative, or unable to determine) or as different systemic or local treatment. If no bone lesions were found by any imaging modality, the patients were included in the analyses without expert review. Results: In total, 3,473 unequivocal bone lesions were identified in 102 evaluated patients (39% by ceCT, 26% by BS, and 87% by 18F-FDG PET). Additional bone lesions on 18F-FDG PET plus ceCT compared with BS plus ceCT led to change in MBC management recommendations in 16% of patients (95% CI, 10%–24%). BS also changed management compared with 18F-FDG PET in 1 patient (1%; 95% CI, 0%–5%). In 26% (95% CI, 19%–36%) of patients, an additional 18F-FDG PET exam was requested, because BS provided insufficient information. Conclusion: In this exploratory analysis of newly diagnosed MBC patients, 18F-FDG PET versus BS to assess bone lesions resulted in clinically relevant management differences in 16% of patients. BS delivered insufficient information in over one fourth of patients, resulting in an additional request for 18F-FDG PET. On the basis of these data, 18F-FDG PET should be considered a primary imaging modality for assessment of bone lesions in newly diagnosed MBC.
The longitudinal trend of hypertension prevalence in Chinese adults from 1959 to 2018: a systematic review and meta-analysis.

BACKGROUND Hypertension is one of the most prevalent non-communicable diseases (NCDs). However, unbalanced regional development and different research designs lead to greater heterogeneity of hypertension data in China, and lack of a summary of long-term variation trends. The aim was to estimate the pooled prevalence of hypertension and to describe the secular trend in hypertension. METHODS Literatures, related to the prevalence of hypertension among Chinese adults, were searched through both English and Chinese databases. The pooled prevalence was estimated with random effects. Subgroup analysis and meta-regression was conducted to address heterogeneity. Continuous fractional polynomial regression model and compound model were used to estimate the trend of hypertension prevalence with time. RESULTS A total of 18 studies were included and the whole population was 9, 191, 121. The pooled prevalence of hypertension among Chinese adults was 24.3% (95% CI: 18.8-29.8%), increasing from the west to the east. Hypertension was more common in male than in female (27.8% vs. 25.1%) and in urban population than in rural population (27.0% vs. 26.0%). The annual increase of prevalence was about 0.29% nonlinearly before 2004 and maintained approximately 2.45% per year between 2004 and 2010. After a significant decline in 2011, there was a slight incline. CONCLUSIONS The prevalence of hypertension in Chinese adults has been increasing, indicating that more efforts should be strengthened for hypertension management in China.
Fixed-Luminance and Multi-Luminance Flicker Electroretinography Parameters in Patients with Early Active Birdshot Chorioretinopathy

ABSTRACT Purpose To evaluate the parameters of the Fixed-Luminance and Multi-Luminance flicker electroretinography protocol among patients with early active birdshot chorioretinopathy. Methods Fixed-Luminance magnitude, Fixed-Luminance phase, Multi-Luminance magnitude area under the curve, and Multi-Luminance phase area under the curve parameters were compared between early active birdshot chorioretinopathy patients and an age-matched control group. Results There was no statistically significant difference between the Fixed-Luminance flicker magnitude (P = .6), the Fixed-Luminance flicker phase (P = .9), and the Multi-Luminance flicker phase area under the curve (P = .55) when each was compared to the normal population; however, the difference between the mean Multi-Luminance flicker magnitude area under the curve in our patients and the healthy control group was statistically significant. (P = .003) Conclusions Multi-Luminance flicker magnitude area under the curve has been shown to be significantly different from the normal population in the early active course of the disease. Abbreviations BSCR: birdshot chorioretinopathy; cd: Cadmium; ERG: Electroretinography; FA: Fluorescein angiography; FL-: Fixed-luminance; HVF: Humphrey visual field; Hz: Hertz; ICG: Indocyanine green; m2: Square meter; ML-: Multi-luminance; ms: millisecond; SITA: Swedish interactive thresholding algorithm; SWAP: Short wave-length automated perimetry
Suicidal Ideation and Behaviors Among High School Students — Youth Risk Behavior Survey, United States, 2019

Suicide is the second leading cause of death among high school-aged youths 14–18 years after unintentional injuries. This report summarizes data regarding suicidal ideation (i.e., seriously considered suicide) and behaviors (i.e., made a suicide plan, attempted suicide, and made a suicide attempt requiring medical treatment) from CDC’s 2019 Youth Risk Behavior Survey. Results are reported overall and by sex, grade, race/ethnicity, sexual identity, and sex of sexual contacts, overall and within sex groups. Trends in suicide attempts during 2009–2019 are also reported by sex, race/ethnicity, and grade. During 2009–2019, prevalence of suicide attempts increased overall and among female, non-Hispanic white, non-Hispanic black, and 12th-grade students. Data from 2019 reflect substantial differences by demographics regarding suicidal ideation and behaviors. For example, during 2019, a total of 18.8% of students reported having seriously considered suicide, with prevalence estimates highest among females (24.1%); white non-Hispanic students (19.1%); students who reported having sex with persons of the same sex or with both sexes (54.2%); and students who identified as lesbian, gay, or bisexual (46.8%). Among all students, 8.9% reported having attempted suicide, with prevalence estimates highest among females (11.0%); black non-Hispanic students (11.8%); students who reported having sex with persons of the same sex or with both sexes (30.3%); and students who identified as lesbian, gay, or bisexual (23.4%). Comprehensive suicide prevention can address these differences and reduce prevalence of suicidal ideation and behaviors by implementing programs, practices, and policies that prevent suicide (e.g., parenting programs), supporting persons currently at risk (e.g., psychotherapy), preventing reattempts (e.g., emergency department follow-up), and attending to persons who have lost a friend or loved one to suicide.
Genetics and geography of leukocyte telomere length in sub-Saharan Africans

Abstract Leukocyte telomere length (LTL) might be causal in cardiovascular disease and major cancers. To elucidate the roles of genetics and geography in LTL variability across humans, we compared LTL measured in 1295 sub-Saharan Africans (SSAs) with 559 African–Americans (AAms) and 2464 European–Americans (EAms). LTL differed significantly across SSAs (P = 0.003), with the San from Botswana (with the oldest genomic ancestry) having the longest LTL and populations from Ethiopia having the shortest LTL. SSAs had significantly longer LTL than AAms [P = 6.5(e-16)] whose LTL was significantly longer than EAms [P = 2.5(e-7)]. Genetic variation in SSAs explained 52% of LTL variance versus 27% in AAms and 34% in EAms. Adjustment for genetic variation removed the LTL differences among SSAs. LTL genetic variation among SSAs, with the longest LTL in the San, supports the hypothesis that longer LTL was ancestral in humans. Identifying factors driving LTL variation in Africa may have important ramifications for LTL-associated diseases.
Multiomic blood correlates of genetic risk identify presymptomatic disease alterations

Significance Most diseases do not develop suddenly, but rather involve the gradual malfunction of physiological processes due to genetic and environmental influences. Here, we study blood measurements from 4,905 individuals and find that people at elevated genetic risk for various diseases have hundreds of detectable changes in blood protein and metabolite levels as well as clinical laboratory tests. These changes tend to also be present in people with the disease, suggesting that they represent early signs of physiological dysfunction occurring before the onset of disease symptoms. Transitions from health to disease are characterized by dysregulation of biological networks under the influence of genetic and environmental factors, often over the course of years to decades before clinical symptoms appear. Understanding these dynamics has important implications for preventive medicine. However, progress has been hindered both by the difficulty of identifying individuals who will eventually go on to develop a particular disease and by the inaccessibility of most disease-relevant tissues in living individuals. Here we developed an alternative approach using polygenic risk scores (PRSs) based on genome-wide association studies (GWAS) for 54 diseases and complex traits coupled with multiomic profiling and found that these PRSs were associated with 766 detectable alterations in proteomic, metabolomic, and standard clinical laboratory measurements (clinical labs) from blood plasma across several thousand mostly healthy individuals. We recapitulated a variety of known relationships (e.g., glutamatergic neurotransmission and inflammation with depression, IL-33 with asthma) and found associations directly suggesting therapeutic strategies (e.g., Ω-6 supplementation and IL-13 inhibition for amyotrophic lateral sclerosis) and influences on longevity (leukemia inhibitory factor, ceramides). Analytes altered in high-genetic-risk individuals showed concordant changes in disease cases, supporting the notion that PRS-associated analytes represent presymptomatic disease alterations. Our results provide insights into the molecular pathophysiology of a range of traits and suggest avenues for the prevention of health-to-disease transitions.
Communication in Pediatric Oncology: A Qualitative Study

In this multicenter study, interviews with parents of children with cancer revealed evidence for 8 communication functions; these communication functions manifested in the context of building relationships. BrightcoveDefaultPlayer10.1542/6166443743001PEDS-VA_2020-1193 Video Abstract BACKGROUND: When children are seriously ill, parents rely on communication with their clinicians. However, in previous research, researchers have not defined how this communication should function in pediatric oncology. We aimed to identify these communication functions from parental perspectives. METHODS: Semistructured interviews with 78 parents of children with cancer from 3 academic medical centers at 1 of 3 time points: treatment, survivorship, or bereavement. We analyzed interview transcripts using inductive and deductive coding. RESULTS: We identified 8 distinct functions of communication in pediatric oncology. Six of these functions are similar to previous findings from adult oncology: (1) building relationships, (2) exchanging information, (3) enabling family self-management, (4) making decisions, (5) managing uncertainty, and (6) responding to emotions. We also identified 2 functions not previously described in the adult literature: (7) providing validation and (8) supporting hope. Supporting hope manifested as emphasizing the positives, avoiding false hopes, demonstrating the intent to cure, and redirecting toward hope beyond survival. Validation manifested as reinforcing “good parenting” beliefs, empowering parents as partners and advocates, and validating concerns. Although all functions seemed to interact, building relationships appeared to provide a relational context in which all other interpersonal communication occurred. CONCLUSIONS: Parent interviews provided evidence for 8 distinct communication functions in pediatric oncology. Clinicians can use this framework to better understand and fulfill the communication needs of parents whose children have serious illness. Future work should be focused on measuring whether clinical teams are fulfilling these functions in various settings and developing interventions targeting these functions.
‘She is like my mother’: Community-based care of drug-resistant tuberculosis in rural Eswatini

ABSTRACT Patients with drug-resistant tuberculosis (DR-TB) have received community-based care in Eswatini since 2009. Trained and compensated community treatment supporters (CTSs) provide directly observed therapy (DOT), injectables and psychological support. We examined the acceptability of this model of care among DR-TB patients, including the perspective of family members of DR-TB patients and their CTSs in relation to the patient’s experience of care and quality of life. This qualitative research was conducted in rural Eswatini in February 2018. DR-TB patients, CTSs and family members participated in in-depth interviews, paired interviews, focus group discussions and PhotoVoice. Data were thematically analysed and coded, and themes were extracted. Methodological triangulation enhanced the interpretation. All patients and CTSs and most family members considered community-based DR-TB care to be supportive. Positive aspects were emotional support, trust and dedicated individual care, including enabling practical, financial and social factors. Concerns were related to social and economic problems within the family and fears about infection risks for the family and the CTSs. Community-based DR-TB care was acceptable to patients, family members and CTSs. To reduce family members’ fears of TB infection, information and sensitisation within the family and constant follow-up appear crucial.
Increased lipid metabolism impairs NK cell function and mediates adaptation to the lymphoma environment.

NK cells play critical roles in protection against haematological malignancies but can acquire a dysfunctional state, which limits anti-tumour immunity. However, the underlying reasons for this impaired NK cell function remain to be uncovered. We found that NK cells in aggressive B cell lymphoma underwent substantial transcriptional reprogramming associated with increased lipid metabolism, including elevated expression of the transcriptional regulator PPAR-g. Exposure to fatty acids in the lymphoma environment potently suppressed NK cell effector response and cellular metabolism. NK cells from both diffuse large B cell lymphoma patients and Eµ-myc B cell lymphoma-bearing mice displayed reduced IFN-g production. Activation of PPAR-g partially restored mitochondrial membrane potential and IFN-g production. Overall our data indicate that increased lipid metabolism, while impairing their function, is a functional adaptation of NK cells to the fatty-acid rich lymphoma environment.
Outcomes of Endoscopic Management among Patients with Bile Leak of Various Etiologies at a Tertiary Care Center

Background/Aims Bile leak is a common complication of cholecystectomy, and it is also observed in other conditions such as ruptured liver abscess, hydatid cyst, and trauma. Endoscopic retrograde cholangiopancreatography (ERCP) is the first-line management for such conditions. However, studies on the outcomes of endoscopic management for bile leaks with etiologies other than post-cholecystectomy injury are extremely limited. Methods We conducted a retrospective review of patients with symptomatic bile leak who were referred to a tertiary care center and who underwent ERCP between April 2016 and April 2019. The primary outcome was complete symptomatic resolution without extravasation of the contrast medium during the second ERCP conducted after 6 weeks. Results In total, 71 patients presented with symptomatic bile leak. The etiologies of bile leak were post-cholecystectomy injury in 34 (47.8%), liver abscess in 20 (28.1%), and post-hydatid cyst surgery in 11 (15.4%) patients. All patients were managed with ERCP, sphincterotomy, and stent placement for 6 weeks, except for one who underwent surgery. The primary outcome was achieved in 65 (91.5%) of 71 patients. There was no significant difference in terms of outcome in relation to the interval between the diagnosis of bile leak and ERCP. Conclusions Most patients with bile leak can be successfully managed with ERCP even when performed on an elective basis.