Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma.

PURPOSE We examined the role of DNA copy number variants (CNVs) of known glaucoma genes in relation to primary open angle glaucoma (POAG). METHODS Our study included DNA samples from two studies (NEIGHBOR and GLAUGEN). All the samples were genotyped with the Illumina Human660W_Quad_v1 BeadChip. After removing non-blood-derived and amplified DNA samples, we applied quality control steps based on the mean Log R Ratio and the mean B allele frequency. Subsequently, data from 3057 DNA samples (1599 cases and 1458 controls) were analyzed with PennCNV software. We defined CNVs as those ≥5 kilobases (kb) in size and interrogated by ≥5 consecutive probes. We further limited our investigation to CNVs in known POAG-related genes, including CDKN2B-AS1, TMCO1, SIX1/SIX6, CAV1/CAV2, the LRP12-ZFPM2 region, GAS7, ATOH7, FNDC3B, CYP1B1, MYOC, OPTN, WDR36, SRBD1, TBK1, and GALC. RESULTS Genomic duplications of CDKN2B-AS1 and TMCO1 were each found in a single case. Two cases carried duplications in the GAS7 region. Genomic deletions of SIX6 and ATOH7 were each identified in one case. One case carried a TBK1 deletion and another case carried a TBK1 duplication. No controls had duplications or deletions in these six genes. A single control had a duplication in the MYOC region. Deletions of GALC were observed in five cases and two controls. CONCLUSIONS The CNV analysis of a large set of cases and controls revealed the presence of rare CNVs in known POAG susceptibility genes. Our data suggest that these rare CNVs may contribute to POAG pathogenesis and merit functional evaluation.
Systemic family therapy is not superior to treatment as usual in preventing repeat self-harm in adolescents

Commentary on : Cottrell DJ, Wright-Hughes A, Collinson M, et al . Effectiveness of systemic family therapy versus treatment as usual for young people after self-harm: a pragmatic, phase 3, multicentre, randomised controlled trial. Lancet Psychiatry 2018;5:203–16. Families influence self-harm in adolescents by either contributing towards it or offering protection against it.1 With limited evidence for individually focused interventions for repeat self-harm in adolescents, evaluation of interventions making use of family’s strengths and resources is a potential option.2 Attachment-based family therapy (ABFT) and multisystem family therapy (MST) are specific family therapy (FT) frameworks that have been tested for self-harm in adolescents.3 ABFT decreased suicidal ideation (secondary outcome) at the end of treatment over 3 months and over 12 weeks of follow-up after completion of treatment.3 MST found a reduction in suicide attempts in adolescents in the home-based …
Association of study quality with completeness of reporting: have completeness of reporting and quality of systematic reviews and meta-analyses in major radiology journals changed since publication of the PRISMA statement?

PURPOSE To evaluate whether completeness of reporting of systematic reviews and meta-analyses in major radiology journals has changed since publication of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement; a secondary objective is to evaluate whether completeness of reporting (ie, PRISMA) is associated with study quality (ie, Assessing the Methodological Quality of Systematic Reviews [AMSTAR]). MATERIALS AND METHODS Systematic reviews and meta-analyses published in major radiology journals between January 2007 and December 2011 were identified by searching MEDLINE with the modified Montori method. Studies were reviewed independently by two investigators and assessed for adherence to the AMSTAR and PRISMA checklists. The average results were analyzed to assess for change in mean score before and after PRISMA publication and to assess results over time; a Pearson correlation coefficient was calculated to assess for any association between PRISMA and AMSTAR results. RESULTS Included were 130 studies from 11 journals. Average PRISMA and AMSTAR results were 21.8 of 27 and 7.2 of 11, respectively. The average result was higher after publication of PRISMA, and PRISMA-reported items were 22.6 of 27 after publication of PRISMA versus 20.9 of 27 before publication of PRISMA; AMSTAR results were 7.7 of 11 after publication of PRISMA versus 6.7 of 11 before publication of PRISMA. There was a strong positive correlation (r = 0.86) between the PRISMA and AMSTAR results. There was high variability between journals. Radiology had the highest PRISMA reported items (24.7 of 27), and American Journal of Neuroradiology had the lowest (19.6 of 27). Two major areas for improvement include study protocol registration and assessment of risk of bias across studies (ie, publication bias). CONCLUSION In major radiology journal studies, there was modest improvement in completeness of reporting of systematic reviews and meta-analyses, assessed by PRISMA, which was strongly associated with higher study quality, assessed by AMSTAR. SUPPLEMENTAL MATERIAL http://radiology.rsna. org/lookup/suppl/doi:10.1148/radiol.13130273/-/DC1.
Environmental Factors Affecting the Severity of Alternaria Brown Spot of Citrus and Their Potential Use in Timing Fungicide Applications.

Alternaria brown spot affects many tangerines and their hybrids, causing lesions on leaves, twigs, and fruit resulting in reduced yield and fruit quality. Field studies were conducted in a severely affected Minneola tangelo grove in central Florida from 1996 to 1998 to determine the environmental factors associated with infection of field trees and potted trap plants. Conidial production peaked following large flushes of new leaves, which were heavily infected. Most infections occurred during the summer rainy season, but trap plants became infected nearly every week of the year. When plants were exposed for 1-week periods, linear regression analysis indicated that disease severity on trap plants was positively related to the amount of rainfall, duration of leaf wetness, and average daily temperatures, and negatively related to the number of conidia trapped. Similar relationships occurred with trap plants exposed for 24-h periods on 141 different dates, except that temperature was not a significant factor. Nevertheless, these factors individually or combined in stepwise multiple regressions explained only a low percentage of the variability in disease severity with both weekly and daily trap plant sampling. When daily environmental data were categorized as: (i) rain versus no rain, (ii) <10 h or >10 h leaf wetness duration, and (iii) average temperature <20°C, 20 to 28°C, and >28°C, relationships to disease severity on trap plants were clearer. Disease severity on days with rain was nearly double that of days without rain, but considerable infection occurred on days with >10 h leaf wetness duration and no rain. Infection was greatest on days with temperatures of 20 to 28°C and slightly less at lower or higher temperatures. A point system, called the ALTER-RATER, was designed whereby each day would be assigned a severity value according to the prevailing environmental conditions. A fungicide application would be made after a predetermined number of points had accumulated. Simulated spray programs based on accumulation of 50, 75, 100, and 150 points from historical weather data at several locations indicated that from 8 to 15, 6 to 8, 5 to 6, or 3 to 4 sprays, respectively, would be needed depending on year and location in Florida. Such a weather-based control system could reduce the number of fungicide applications and improve control of Alternaria brown spot of tangerine.
Incidence and relative risk for developing cancers in women with gestational diabetes mellitus: a nationwide cohort study in Taiwan

Objectives To evaluate the risk of developing cancers, particularly site-specific cancers, in women with gestational diabetes mellitus (GDM) in Taiwan. Setting The National Health Insurance Research Database (NHIRD) of Taiwan. Participants This study was conducted using the nationwide data from 2000 to 2013. In total, 1 466 596 pregnant women with admission for delivery were identified. Subjects with GDM consisted of 47 373 women, while the non-exposed group consisted of 943 199 women without GDM. The participants were followed from the delivery date to the diagnosis of cancer, death, the last medical claim or the end of follow-up (31 December 2013), whichever came first. Primary outcome measures Patients with a new diagnosis of cancer (International Classification of Diseases, ninth edition, with clinical modification (ICD-9-CM codes 140–208)) recorded in NHIRD were identified. The risk of 11 major cancer types was assessed, including cancers of head and neck, digestive organs, lung and bronchus, bone and connective tissue, skin, breast, genital organs, urinary system, brain, thyroid gland and haematological system. Results The rates of developing cancers were significantly higher in women with GDM compared with the non-GDM group (2.24% vs 1.96%; p<0.001). After adjusting for maternal age at delivery and comorbidities, women with GDM had increased risk of cancers, including cancers of nasopharynx (adjusted HR, 1.739; 95 % CI, 1.400 to 2.161; p<0.0001), kidney (AHR, 2.169; 95 % CI, 1.428 to 3.293; p=0.0003), lung and bronchus (AHR, 1.372; 95 % CI, 1.044 to 1.803; p=0.0231), breast (AHR, 1.234; 95% CI, 1.093 to 1.393; p=0.007) and thyroid gland (AHR, 1.389; 95 % CI, 1.121 to 1.721; p=0.0026). Conclusion Women with GDM have a higher risk of developing cancers. Cancer screening is warranted in women with GDM. Future research should be aimed at establishing whether this association is causal.
Severe Depressive Episode with Psychotic Symptoms and Type 2 Diabetes: A 2010–2017 Longitudinal Study

Background There have been few studies published on the prevalence of severe depressive episode in people with type 2 diabetes (T2DM) or its role in adherence to dietary recommendations. We examined the Polish National Health Fund (NFZ) database estimates of all medical visits from 2010 to 2017 to determine the trend and the epidemiology of severe depressive episode in T2DM. Material/Methods The NFZ database was used. We defined the T2DM group diagnosed with both T2DM and severe depressive episode according to the ICD-10 codes. The annual prevalence of severe depressive episode was estimated according to the T2DM diagnosis status, and the age groups were stratified into 8 groups. Results Relative risk for depression (regardless of severity of symptoms) in T2DM is 1.347 [95%CI: 1.342–1.353]. The frequency trend of severe depressive episode with or without psychotic symptoms remains relatively stable. In the case of mild and moderate depressive episode, a downward trend was noted, but they are still the most frequent mood disorders diagnosed. Patients with T2DM aged 20 to 40, for whom the peak of coexistence of these illnesses was noted, are the group particularly vulnerable to depression. Depression also remains on a relatively high but stable level for patients over 60 years of age. Conclusions The coexistence of depressive episodes in T2DM is a key challenge for medicine and public health. Measures aimed at early identification of patients with T2DM prone to depression need to be taken. Creating multidisciplinary care teams in diabetes management is also necessary.
Usefulness and Limitations of Comprehensive Characterization of mRNA Splicing Profiles in the Definition of the Clinical Relevance of BRCA1/2 Variants of Uncertain Significance

Highly penetrant variants of BRCA1/2 genes are involved in hereditary predisposition to breast and ovarian cancer. The detection of pathogenic BRCA variants has a considerable clinical impact, allowing appropriate cancer-risk management. However, a major drawback is represented by the identification of variants of uncertain significance (VUS). Many VUS potentially affect mRNA splicing, making transcript analysis an essential step for the definition of their pathogenicity. Here, we characterize the impact on splicing of ten BRCA1/2 variants. Aberrant splicing patterns were demonstrated for eight variants whose alternative transcripts were fully characterized. Different events were observed, including exon skipping, intron retention, and usage of de novo and cryptic splice sites. Transcripts with premature stop codons or in-frame loss of functionally important residues were generated. Partial/complete splicing effect and quantitative contribution of different isoforms were assessed, leading to variant classification according to Evidence-based Network for the Interpretation of Mutant Alleles (ENIGMA) consortium guidelines. Two variants could be classified as pathogenic and two as likely benign, while due to a partial splicing effect, six variants remained of uncertain significance. The association with an undefined tumor risk justifies caution in recommending aggressive risk-reduction treatments, but prevents the possibility of receiving personalized therapies with potential beneficial effect. This indicates the need for applying additional approaches for the analysis of variants resistant to classification by gene transcript analyses.
Mapping cultural tightness and its links to innovation, urbanization, and happiness across 31 provinces in China

Significance This study extends existing theories of cultural tightness by mapping cultural tightness and its relationship to innovation across 31 provinces in China. Consistent with prior research, we find that tighter provinces are associated with increased governmental control, constraints in daily life, religious practices, and exposure to threats. However, prior findings about cultural tightness do not fully apply to China. Departing from prior findings that tighter states are more rural, conservative, less creative, and less happy, cultural tightness in China is associated with urbanization; economic growth; better health; greater happiness; tolerance toward the lesbian, gay, bisexual, and transgender community; and gender equality. Provinces with tight cultures exhibit lower rates of substantive/radical innovation yet higher rates of incremental innovation. We conduct a 3-y study involving 11,662 respondents to map cultural tightness—the degree to which a society is characterized by rules and norms and the extent to which people are punished or sanctioned when they deviate from these rules and norms—across 31 provinces in China. Consistent with prior research, we find that culturally tight provinces are associated with increased governmental control, constraints in daily life, religious practices, and exposure to threats. Departing from previous findings that tighter states are more rural, conservative, less creative, and less happy, cultural tightness in China is associated with urbanization, economic growth, better health, greater tolerance toward the LGBT (lesbian, gay, bisexual, and transgender) community, and gender equality. Further, analyzing about 3.85 million granted patents in China (1990–2013), we find that provinces with tighter cultures have lower rates of substantive/radical innovations yet higher rates of incremental innovations; individuals from culturally tighter provinces reported higher levels of experienced happiness.
Emotions, bodily changes, and the social environment: How did early psychosomatic medicine consider the social dimension in health and disease?

OBJECTIVE Social relationships play an important role in human health and disease processes, and the field of psychosomatic medicine currently integrates social factors in its theoretical models and clinical interventions. This article provides a historical perspective on the field of psychosomatic medicine in the United States and examines the extent to which early American psychosomatic medicine incorporated the impact of social relationships on health and disease outcomes. METHODS We searched pubmed across all issues of Psychosomatic Medicine for key words related to emotions vs. social processes. Article counts are compared for these key words. We then performed a narrative review to analyze how concepts of associations among emotional, interpersonal, and physiological variables evolved in early publications. RESULTS Of 5,023 articles found in Psychosomatic Medicine, 1,453 contained an emotional, 936 a social search term, and 447 contained both. In the qualitative review, influences of the social environment on emotional states and physiology were recognized already in the 1930s but they only played a subordinate role in early Psychosomatic Medicine. Publications often lacked a clear working model how interpersonal events exert their impact on physiology. With increasing understanding of developmental and neural mechanisms, a more differentiated view evolved. CONCLUSION Early publications in psychosomatic medicine mainly focused on associations between emotions and physiology. However, some highlighted the importance of interpersonal and social factors. Later, the understanding of emotions, social relationships and physiology with their developmental and neurobiological correlates have led to a fuller "biopsychosociocultural" understanding of health and disease, although more research on and within these networks is urgently needed.
Limitations and ceiling effects with circumferential minimally invasive correction techniques for adult scoliosis: analysis of radiological outcomes over a 7-year experience.

OBJECT Minimally invasive correction of adult scoliosis is a surgical method increasing in popularity. Limited data exist, however, as to how effective these methodologies are in achieving coronal plane and sagittal plane correction in addition to improving spinopelvic parameters. This study serves to quantify how much correction is possible with present circumferential minimally invasive surgical (cMIS) methods. METHODS Ninety patients were selected from a database of 187 patients who underwent cMIS scoliosis correction. All patients had a Cobb angle greater than 15°, 3 or more levels fused, and availability of preoperative and postoperative 36-inch standing radiographs. The mean duration of follow-up was 37 months. Preoperative and postoperative Cobb angle, sagittal vertical axis (SVA), coronal balance, lumbar lordosis (LL), and pelvic incidence (PI) were measured. Scatter plots were performed comparing the pre- and postoperative radiological parameters to calculate ceiling effects for SVA correction, Cobb angle correction, and PI-LL mismatch correction. RESULTS The mean preoperative SVA value was 60 mm (range 11.5-151 mm); the mean postoperative value was 31 mm (range 0-84 mm). The maximum SVA correction achieved with cMIS techniques in any of the cases was 89 mm. In terms of coronal Cobb angle, a mean correction of 61% was noted, with a mean preoperative value of 35.8° (range 15°-74.7°) and a mean postoperative value of 13.9° (range 0°-32.5°). A ceiling effect for Cobb angle correction was noted at 42°. The ability to correct the PI-LL mismatch to 10° was limited to cases in which the preoperative PI-LL mismatch was 38° or less. CONCLUSIONS Circumferential MIS techniques as currently used for the treatment of adult scoliosis have limitations in terms of their ability to achieve SVA correction and lumbar lordosis. When the preoperative SVA is greater than 100 mm and a substantial amount of lumbar lordosis is needed, as determined by spinopelvic parameter calculations, surgeons should consider osteotomies or other techniques that may achieve more lordosis.
Clinical effect of balloon kyphoplasty in elderly patients with multiple osteoporotic vertebral fracture

Objective: This study aims to discuss the clinical effect of balloon kyphoplasty on elderly patients with multiple osteoporotic vertebral fractures. Methods: The observation group was treated with balloon kyphoplasty, and the control group was managed with conservative treatment. Image indices, pain degree, daily life disturbance, and occurrences of complications were compared between the two groups. Results: In total, 116 elderly patients with multiple osteoporotic vertebral fracture admitted in our hospital from January 2016 to June 2017 were chosen and divided randomly into observation (n = 58) and control groups (n = 58). The observation group showed a significantly higher trailing edge, leading edge, and midcourt line and larger upper thoracic kyphosis compared with the control group (P < 0.05). Before the treatment, no statistically significant differences were observed between the two groups in terms of visual analog scale (VAS) score and daily life disturbance score (P > 0.05). However, the VAS score and the daily life disturbance score of the two groups decreased sharply after the treatment (P < 0.05). Moreover, the VAS score and the daily life disturbance score of the observation group were significantly lower than those of the control group (P < 0.05). The observation group showed lower occurrence rate of complications compared with the control group (P < 0.05). Conclusions: Balloon kyphoplasty can significantly improve the image indices of patients with multiple osteoporotic vertebral fractures and relieve their pain degree and daily life disturbance. Balloon kyphoplasty exhibited a low occurrence rate of complications and high safety and is, thus, worthy of clinical applications.
Loss of Trefoil Factor 2 Sensitizes Rat Pups to Systemic Infection with the Neonatal Pathogen Escherichia coli K1

Gastrointestinal (GI) colonization of 2-day-old (P2) rat pups with Escherichia coli K1 results in translocation of the colonizing bacteria across the small intestine, bacteremia, and invasion of the meninges, with animals frequently succumbing to lethal infection. Infection, but not colonization, is strongly age dependent; pups become progressively less susceptible to infection over the P2-to-P9 period. ABSTRACT Gastrointestinal (GI) colonization of 2-day-old (P2) rat pups with Escherichia coli K1 results in translocation of the colonizing bacteria across the small intestine, bacteremia, and invasion of the meninges, with animals frequently succumbing to lethal infection. Infection, but not colonization, is strongly age dependent; pups become progressively less susceptible to infection over the P2-to-P9 period. Colonization leads to strong downregulation of the gene encoding trefoil factor 2 (Tff2), preventing maturation of the protective mucus barrier in the small intestine. Trefoil factors promote mucosal homeostasis. We investigated the contribution of Tff2 to protection of the neonatal rat from E. coli K1 bacteremia and tissue invasion. Deletion of tff2, using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, sensitized P9 pups to E. coli K1 bacteremia. There were no differences between tff2−/− homozygotes and the wild type with regard to the dynamics of GI colonization. Loss of the capacity to elaborate Tff2 did not impact GI tract integrity or the thickness of the small-intestinal mucus layer but, in contrast to P9 wild-type pups, enabled E. coli K1 bacteria to gain access to epithelial surfaces in the distal region of the small intestine and exploit an intracellular route across the epithelial monolayer to enter the blood circulation via the mesenteric lymphatic system. Although primarily associated with the mammalian gastric mucosa, we conclude that loss of Tff2 in the developing neonatal small intestine enables the opportunistic neonatal pathogen E. coli K1 to enter the compromised mucus layer in the distal small intestine prior to systemic invasion and infection.