Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinicopathologic features and prognostic significance of CD30 expression in de novo diffuse large B-cell lymphoma (DLBCL): results in a homogeneous series from a single institution

Abstract Introduction: The present study evaluates CD30 expression by immunohistochemistry (IHQ) in 216 patients with de novo DLBCL. Methods: CD30 expression was assessed retrospectively in all cases by IHQ. More than >0% and >20% of CD30 expression in the malignant cells were used as a cut-off for positivity. Survival was analysed in 176 patients treated with R-CHOP/R-CHOP-like regimens. Results: CD30 expression >0% was found in 66 (31%) patients, and >20% in 41 (19%). Younger patients <60 years (p = 0.03), good performance status (p = 0.04), and non-GCB subtype (p = 0.004) correlated with CD30 expression. No significant differences were found in overall survival and progression-free survival (PFS), although there was a trend towards better PFS in CD30-positive patients (p = 0.07). Among 7 patients with Epstein-Barr virus (EBV)-positive-DLBCL, CD30 was expressed in 71%, and 2-year PFS significantly inferior compared with CD30-positive EBV-negative-DLBCL patients (p = 0.01). Conclusion: CD30 is expressed in 30% of DLBCL patients, in whom targeted therapy with an anti-CD30 monoclonal antibody could be explored. CD30 is expressed more frequently younger patients, with better performance status and in the non-GCB subtype and its expression trends towards a better PFS. No significant differences regarding characteristics at diagnosis or prognosis were found between groups with different cut-off for positivity.
The impact of interpregnancy weight change on perinatal outcomes in women and their children: A systematic review and meta‐analysis

Prepregnancy overweight and obesity are associated with higher risk of perinatal complications. However, the effect of weight change prior to pregnancy on perinatal outcome is largely unknown. Therefore, it is aimed to examine the impact on perinatal outcomes of interpregnancy BMI change in women of different BMI categories. The MEDLINE, EMBASE, LILACS, and CINAHL databases were searched (1990‐August 2019). Observational studies on interpregnancy BMI change were selected. Outcomes evaluated were gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension (GH), cesarean section, preterm birth, and newborns being large (LGA) or small (SGA) for gestational age. Meta‐analyses and meta‐regression analyses were executed. Thirty studies were included (n > 1 million). Interpregnancy BMI gain was associated with a higher risk of GDM (for BMI gain ≥3 kg/m2: OR 2.21; [95%CI 1.53‐3.19]), preeclampsia (1.77 [1.53‐2.04]), GH (1.78 [1.61‐1.97]), cesarean section (1.32 [1.24‐1.39]), and LGA (1.54 [1.28‐1.86]). The effects of BMI gain were most pronounced in women with BMI <25 kg/m2 before the first pregnancy regarding GDM, GH, and cesarean section. Except for LGA, interpregnancy BMI loss did not result in a decreased risk of perinatal complications. In this study, women of normal weight who gain weight before pregnancy were identified as a high‐risk population for perinatal complications. This emphasizes that weight management is important for women of all BMI categories and a pregnancy wish.
Coding and Non-Coding RNA Abnormalities in Bipolar Disorder

The molecular mechanisms underlying bipolar disorder (BPD) have remained largely unknown. Postmortem brain tissue studies comparing BPD patients with healthy controls have produced a heterogeneous array of potentially implicated protein-coding RNAs. We hypothesized that dysregulation of not only coding, but multiple classes of RNA (coding RNA, long non-coding (lnc) RNA, circular (circ) RNA, and/or alternative splicing) underlie the pathogenesis of BPD. Using non-polyadenylated libraries we performed RNA sequencing in postmortem human medial frontal gyrus tissue from BPD patients and healthy controls. Twenty genes, some of which not previously implicated in BPD, were differentially expressed (DE). PCR validation and replication confirmed the implication of these DE genes. Functional in silico analyses identified enrichment of angiogenesis, vascular system development and histone H3-K4 demethylation. In addition, ten lncRNA transcripts were differentially expressed. Furthermore, an overall increased number of alternative splicing events in BPD was detected, as well as an increase in the number of genes carrying alternative splicing events. Finally, a large reservoir of circRNAs populating brain tissue not affected by BPD is described, while in BPD altered levels of two circular transcripts, cNEBL and cEPHA3, are reported. cEPHA3, hitherto unlinked to BPD, is implicated in developmental processes in the central nervous system. Although we did not perform replication analyses of non-coding RNA findings, our findings hint that RNA dysregulation in BPD is not limited to coding regions, opening avenues for future pharmacological investigations and biomarker research.
일 대학병원 소아중환자실에서 Modified Glasgow Coma Scale 적용의 객관성 검증

Purpose: Rapid and accurate assessment of impaired consciousness is very important, especially for critically ill patients. Therefore, the Glasgow coma scale (GCS) has been widely adopted in the assessment of adult and pediatric comas. But the GCS should not be used for small children who show various normal responses according to their developmental stage. Therefore, the objectivity of pediatric coma measurements was verified by applying the modified GCS to patients in a pediatric intensive care unit (PICU) at a university hospital in Korea. Methods: The level of consciousness was evaluated for 200 cases who were admitted to a PICU from July 4, 2009 to September 18, 2009 and could show a verbal response, with our modified GCS for children. In addition, and we confirmed the frequency analysis and Kappa statistics with SPSS/WIN 17.0. Results: Kappa statistics which show inter-observer reliability were very good for all components (eye opening, verbal, and motor score) and was good for total GCS scores. Conclusion: It is concluded that our modified GCS is reliable. Therefore, reliable assessment for the level of consciousness is clinically practicable if enough training is supported.
Advanced-stage anaplastic large-cell lymphoma in children and adolescents: Results of ANHL0131, a randomized phase III trial with standard APO (doxorubicin, prednisone, vincristine) versus consolidation with a regimen including vinblastine: A report from the Children's Oncology Group.

9511 Background: Anaplastic large cell lymphomas (ALCL) comprise 10-15% of childhood non-Hodgkin lymphomas. Children with advanced-stage (Murphy III and IV) ALCL have a 2-year survival in the range of 70-80%. Vinblastine (VBL) as a single agent has resulted in durable responses in children with relapsed ALCL. Methods: ANHL0131 examined whether a consolidation regimen adding VBL to the standard APO (doxorubicin, prednisone and vincristine) regimen would result in superior event-free survival (EFS). The study was open to Murphy stage III/IV with CD30+ ALCL under age 21. Induction was identical for both arms. Patients were randomized to either receive standard APO therapy with vincristine every 3 weeks during consolidation or a regimen substituting weekly VBL for vincristine (APV). Total length of therapy was 1 year. Stringent criteria were followed to monitor and reduce VBL if increased toxicity was observed. The initial starting dose was 6 mg/m2 and was subsequently reduced to 4 mg/m2. Results: 118 eligibl.
Does source credibility matter for point-of-decision prompts? A quasi-experimental field study to increase stair use

A quasi-experimental field study was undertaken to examine whether the source credibility of point-of-decision (POD) prompts would affect their effectiveness in increasing stair use. POD prompts attributed either to a more credible source, a less credible source, or nothing were randomly installed in three student halls of residence at a public university in Hong Kong (plus a control). The stair and elevator use of residents were recorded by view-from-top surveillance cameras and counted using motion-detection software, resulting in 14,189 observations. The findings show that all the POD prompts can yield, as hypothesized, a significant positive effect on stair use. The relative increase in stair use was 2.49% on average. However, contrary to our second hypothesis, the POD prompt attributed to the more credible source was not the most effective intervention. The implications of these findings are discussed in conclusion.
In vivo force–length and activation dynamics of two distal rat hindlimb muscles in relation to gait and grade

ABSTRACT Muscle function changes to meet the varying mechanical demands of locomotion across different gait and grade conditions. A muscle's work output is determined by time-varying patterns of neuromuscular activation, muscle force and muscle length change, but how these patterns change under different conditions in small animals is not well defined. Here, we report the first integrated in vivo force–length and activation patterns in rats, a commonly used small animal model, to evaluate the dynamics of two distal hindlimb muscles (medial gastrocnemius and plantaris) across a range of gait (walk, trot and gallop) and grade (level and incline) conditions. We use these data to explore how the pattern of force production, muscle activation and muscle length changes across conditions in a small quadrupedal mammal. As hypothesized, we found that the rat muscles show limited fascicle strains during active force generation in stance across gaits and grades, indicating that these distal rat muscles generate force economically but perform little work, similar to patterns observed in larger animals during level locomotion. Additionally, given differences in fiber type composition and variation in motor unit recruitment across the gait and grade conditions examined here for these muscles, the in vivo force–length behavior and neuromuscular activation data reported here can be used to validate improved two-element Hill-type muscle models. Summary: Similar to the patterns observed in larger animals, distal rat muscles favor economy and show limited fascicle strains across gaits and grades.
Suppression of enteroendocrine cell glucagon-like peptide (GLP)-1 release by fat-induced small intestinal ketogenesis: a mechanism targeted by Roux-en-Y gastric bypass surgery but not by preoperative very-low-calorie diet

Objective Food intake normally stimulates release of satiety and insulin-stimulating intestinal hormones, such as glucagon-like peptide (GLP)-1. This response is blunted in obese insulin resistant subjects, but is rapidly restored following Roux-en-Y gastric bypass (RYGB) surgery. We hypothesised this to be a result of the metabolic changes taking place in the small intestinal mucosa following the anatomical rearrangement after RYGB surgery, and aimed at identifying such mechanisms. Design Jejunal mucosa biopsies from patients undergoing RYGB surgery were retrieved before and after very-low calorie diet, at time of surgery and 6 months postoperatively. Samples were analysed by global protein expression analysis and Western blotting. Biological functionality of these findings was explored in mice and enteroendocrine cells (EECs) primary mouse jejunal cell cultures. Results The most prominent change found after RYGB was decreased jejunal expression of the rate-limiting ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHMGCS), corroborated by decreased ketone body levels. In mice, prolonged high-fat feeding induced the expression of mHMGCS and functional ketogenesis in jejunum. The effect of ketone bodies on gut peptide secretion in EECs showed a ∼40% inhibition of GLP-1 release compared with baseline. Conclusion Intestinal ketogenesis is induced by high-fat diet and inhibited by RYGB surgery. In cell culture, ketone bodies inhibited GLP-1 release from EECs. Thus, we suggest that this may be a mechanism by which RYGB can remove the inhibitory effect of ketone bodies on EECs, thereby restituting the responsiveness of EECs resulting in increased meal-stimulated levels of GLP-1 after surgery.
Burden of Disease Estimates of Seven Pathogens Commonly Transmitted Through Foods in Denmark, 2017.

Burden of disease metrics is increasingly established to prioritize food safety interventions. We estimated the burden of disease caused by seven foodborne pathogens in Denmark in 2017: Campylobacter, Salmonella, Shiga toxin-producing Escherichia coli, norovirus, Yersinia enterocolitica, Listeria monocytogenes, and Toxoplasma gondii. We used public health surveillance data and scientific literature to estimate incidence, mortality, and total disability-adjusted life year (DALY) of each, and linked results with estimates of the proportion of disease burden that is attributable to foods. Our estimates showed that Campylobacter caused the highest burden of disease, leading to a total burden of 1709 DALYs (95% uncertainty interval [UI] 1665-1755), more than threefold higher than the second highest ranked pathogen (Salmonella: 492 DALYs; 95% UI 481-504). Campylobacter still led the ranking when excluding DALYs attributable to nonfoodborne routes of exposure. The total estimated incidence was highest for norovirus, but this agent ranked sixth when focusing on foodborne burden. Salmonella ranked second in terms of foodborne burden of disease, followed by Listeria and Yersinia. Foodborne congenital toxoplasmosis was estimated to cause the loss of ∼100 years of healthy life, a burden that was borne by a low number of cases in the population. The ranking of foodborne pathogens varied substantially when based on reported cases, estimated incidence, and burden of disease estimates. Our results reinforce the need to continue food safety efforts throughout the food chain in Denmark, with a particular focus on reducing the incidence of Campylobacter infections.
Motor Cortex Inputs at the Optimum Phase of Beta Cortical Oscillations Undergo More Rapid and Less Variable Corticospinal Propagation

Brain oscillations involve rhythmic fluctuations of neuronal excitability and may play a crucial role in neural communication. The human corticomuscular system is characterized by beta activity and is readily probed by transcranial magnetic stimulation (TMS). TMS inputs arriving at the excitable phase of beta oscillations in the motor cortex are known to lead to muscle responses of greater amplitude. Here we explore two other possible manifestations of rhythmic excitability in the beta band; windows of reduced response variability and shortened latency. We delivered single-pulse TMS to the motor cortex of healthy human volunteers (10 females and 7 males) during electroencephalography recordings made at rest. TMS delivered at a particular phase of the beta oscillation benefited from not only stronger, but also less variable and more rapid transmission, as evidenced by the greater amplitude, lower coefficient of variation, and shorter latency of motor evoked potentials. Thus, inputs aligned to the optimal phase of the beta EEG in the motor cortex enjoy transmission amplitude gain, but may also benefit from less variability and shortened latencies at subsequent synapses. Neuronal phase may therefore impact corticospinal communication. SIGNIFICANCE STATEMENT Brain oscillations involve rhythmic fluctuations of neuronal excitability. Therefore, motor responses to transcranial magnetic stimulation are larger when a cortical input arrives at a particular phase of the beta activity in the motor cortex. Here, we demonstrate that inputs to corticospinal neurons which coincide with windows of higher excitability also benefit from more rapid and less variable corticospinal transmission. This shortening of latency and increased reproducibility may confer additional advantage to inputs at specific phases. Moreover, these benefits are conserved despite appreciable corticospinal conduction delays.
Unimodal and Bimodal Access to Sensory Working Memories by Auditory and Visual Impulses

It is unclear to what extent sensory processing areas are involved in the maintenance of sensory information in working memory (WM). Previous studies have thus far relied on finding neural activity in the corresponding sensory cortices, neglecting potential activity-silent mechanisms, such as connectivity-dependent encoding. It has recently been found that visual stimulation during visual WM maintenance reveals WM-dependent changes through a bottom-up neural response. Here, we test whether this impulse response is uniquely visual and sensory-specific. Human participants (both sexes) completed visual and auditory WM tasks while electroencephalography was recorded. During the maintenance period, the WM network was perturbed serially with fixed and task-neutral auditory and visual stimuli. We show that a neutral auditory impulse-stimulus presented during the maintenance of a pure tone resulted in a WM-dependent neural response, providing evidence for the auditory counterpart to the visual WM findings reported previously. Interestingly, visual stimulation also resulted in an auditory WM-dependent impulse response, implicating the visual cortex in the maintenance of auditory information, either directly or indirectly, as a pathway to the neural auditory WM representations elsewhere. In contrast, during visual WM maintenance, only the impulse response to visual stimulation was content-specific, suggesting that visual information is maintained in a sensory-specific neural network, separated from auditory processing areas. SIGNIFICANCE STATEMENT Working memory is a crucial component of intelligent, adaptive behavior. Our understanding of the neural mechanisms that support it has recently shifted: rather than being dependent on an unbroken chain of neural activity, working memory may rely on transient changes in neuronal connectivity, which can be maintained efficiently in activity-silent brain states. Previous work using a visual impulse stimulus to perturb the memory network has implicated such silent states in the retention of line orientations in visual working memory. Here, we show that auditory working memory similarly retains auditory information. We also observed a sensory-specific impulse response in visual working memory, while auditory memory responded bimodally to both visual and auditory impulses, possibly reflecting visual dominance of working memory.
Measuring Faecal Glucocorticoid Metabolites to Assess Adrenocortical Activity in Reindeer

Simple Summary We validated an 11-oxoaetiocholanolone enzyme immunoassay for measuring faecal cortisol metabolites (FCMs) in reindeer. Samples were collected from eight male reindeer following adrenocorticotrophic hormone (ACTH) stimulation and from another group of reindeer during handling and calf marking. The overall FCM levels peaked after seven to eight hours in both locations, proving that the assay is suited to evaluate the adrenocortical activity in reindeer. Abstract Several non-invasive methods for assessing stress responses have been developed and validated for many animal species. Due to species-specific differences in metabolism and excretion of stress hormones, methods should be validated for each species. The aim of this study was to conduct a physiological validation of an 11-oxoaetiocholanolone enzyme immunoassay (EIA) for measuring faecal cortisol metabolites (FCMs) in male reindeer by administration of adrenocorticotrophic hormone (ACTH; intramuscular, 0.25 mg per animal). A total of 317 samples were collected from eight male reindeer over a 44 h period at Tverrvatnet in Norway in mid-winter. In addition, 114 samples were collected from a group of reindeer during normal handling and calf marking at Stjernevatn in Norway. Following ACTH injection, FCM levels (median and range) were 568 (268–2415) ng/g after two hours, 2718 (414–8550) ng/g after seven hours and 918 (500–6931) ng/g after 24 h. Levels were significantly higher from seven hours onwards compared to earlier hours (p < 0.001). The FCM levels at Stjernevatn were significantly (p < 0.001) different before (samples collected zero to two hours; median: 479 ng/g) and after calf marking (eight to ten hours; median: 1469 ng/g). Identification of the faecal samples belonging to individual animals was conducted using DNA analysis across time. This study reports a successful validation of a non-invasive technique for measuring stress in reindeer, which can be applied in future studies in the fields of biology, ethology, ecology, animal conservation and welfare.
Anal squamous intraepithelial lesions (aSIL) in HIV-positive MSM: incidence and risk factors of aSIL, and of progression and clearance of low-grade aSIL.

BACKGROUND HIV-positive men who have sex with men (MSM) are at risk for developing anal squamous cell carcinoma. Data on the natural history of the precursor, anal squamous intraepithelial lesions (SIL), are limited. METHODS HIV-positive MSM were screened for histopathological SIL by high resolution anoscopy. For participants without SIL at baseline we estimated the cumulative incidence and risk factors of SIL. For participants with low-grade SIL (LSIL) at baseline, risk of progression to high-grade SIL (HSIL) and the clearance rate were estimated at lesion level. RESULTS Of 807 men without SIL at baseline, 107 had a second HRA between 1-4.5 years. At the second visit 18 men (16.8%) showed LSIL, and 25 (23.4%) HSIL. Age was associated with incident LSIL (adjusted odds ratio (aOR) 2.10 per 10 year older, p=0.012). Of 393 men with LSIL at baseline, 114 had a second HRA between 0.5-2.5 years. Eighty-seven (49.2%) of the 177 LSIL lesions found at baseline had cleared at the second visit; 29 (16.4%) had progressed to HSIL. CONCLUSION Incident LSIL and HSIL were common during follow-up among HIV-positive MSM without dysplasia at baseline. Among men with LSIL at baseline, nearly half of these lesions cleared, while a small portion progressed.
Lived experiences of health problems of elderly residing in urban areas, Kathmandu: Pilot Study

Introduction: Globally, number of old age population is increasing with advancement of biomedical technology. Old age is the time associated with biological, psychological and social changes which situate elderly to acquire different health related problems. Objectives: To find out lived experiences of elderly regarding their health problems residing in homes of Kathmandu city. Methods: Qualitative hermeneutic phenomenology approach was adopted. Researcher selected purposively four elderly residing in an urban area of Kathmandu Valley as the study participants. In-depth interview was conducted by using in-depth interview guideline, as well as medical records, field notes and observation clues were recorded. Interview was conducted in Nepali Language and was audio taped. The recording was transcribed by the researcher herself, and the data were analyzed thematically. Finally, different sources of data were triangulated. Results: The four main themes identified were physical health problems, impaired functional abilities, psychological and social problems. Experienced physical health problems were joint pain, hearing and vision deficit, chronic obstructive pulmonary disease, diabetes, gastritis and fall injury. Impaired Functional abilities in performing activities of daily living was commonly experienced problems. Loneliness and decreased recent memory power were the psychological problems. Being neglected by family members, financial constraints for treatment and improper care during illness were the discerned social problems. Conclusion: Elderly are suffering from different physical health problems, impaired functional abilities, as well as various psycho-social problems. Thus, health promotional activities need to be promoted for decreasing morbidity of elderly. Family members need to be focused in the care of elderly through national policy.