Miracle-dz/UniFAR-FTUs huggingface dataset:
Pancreatic Solid Pseudopapillary Neoplasm: Key Pathologic and Genetic Features.

CONTEXT. — Solid pseudopapillary neoplasm of the pancreas is a low-grade malignant tumor generally associated with a good prognosis. Solid pseudopapillary neoplasms show peculiar morphologic features, but sometimes the differential diagnosis with other pancreatic neoplasms (ie, pancreatic neuroendocrine tumors) can be a challenging task, especially in cytologic or biopsy specimens. In these cases immunohistochemistry is a useful tool, but the diagnostic utility of several proposed immunohistochemical markers is questionable. In recent years, despite several attempts to characterize the pathogenetic, molecular, and prognostic features of solid pseudopapillary neoplasms, they still remain unclear. OBJECTIVE. — To give the reader a comprehensive update on this entity. DATA SOURCES. — The PubMed database (US National Library of Medicine) was searched using the following string: pseudopapillary tumor [AND/OR] neoplasm [AND/OR] pancreas. All articles written in English were included. In addition, because a heterogeneous terminology has been used in the past to define solid pseudopapillary neoplasms, the reference lists of each paper selected in the PubMed database were also reviewed. CONCLUSIONS. — This review gives a comprehensive update on the pathologic, clinical, and molecular features of SPNs, particularly addressing issues and challenges related to diagnosis. In addition, we have tried to correlate the molecular alterations with the morphologic and clinical features.
Short-term effects of two deep dry needling techniques on pressure pain thresholds and electromyographic amplitude of the lumbosacral multifidus in patients with low back pain - a randomized clinical trial

ABSTRACT Objectives: The purpose of this study was to compare the effects of deep dry needling (DN) with and without needle manipulation on pressure pain thresholds (PPTs) and electromyographic (EMG) amplitude of the lumbosacral multifidus (LM) in adults with low back pain (LBP). Methods: Participants were randomized into two treatment groups: with needle manipulation (n = 21) and without needle manipulation (n = 21). All participants received a single session of the assigned DN intervention. PPTs and EMG amplitude of the LM muscle were collected three times: before DN, immediately after DN, and one week after DN. Results: The needle manipulation group had a significantly greater increase in PPT immediately after the intervention and at the one-week follow-up as compared to the no needle manipulation group. The increase of PPT in the needle manipulation group was significant immediately after the intervention, and the increase remained significant at the one-week follow-up. However, there was no significant difference in EMG amplitude of the LM muscle between groups across the three time points. Discussion: Deep DN with needle manipulation appeared to reduce mechanical pressure sensitivity more than DN without manipulation for patients with LBP. Although a single session of DN could reduce pressure pain sensitivity, it may not be sufficient to improve LM muscle function. Level of Evidence: 1b. Trial registration numbers: NCT03970486.
Influence of dual‐specificity protein phosphatase 5 on mechanical properties of rat cerebral and renal arterioles

We recently reported that KO of Dual‐specificity protein phosphatase 5 (Dusp5) enhances myogenic reactivity and blood flow autoregulation in the cerebral and renal circulations in association with increased levels of pPKC and pERK1/2 in the cerebral and renal arteries and arterioles. In the kidney, hypertension‐related renal damage was significantly attenuated in Dusp5 KO rats. Elevations in pPKC and pERK1/2 promote calcium influx in VSMC and facilitate vasoconstriction. However, whether DUSP5 plays a role in altering the passive mechanical properties of cerebral and renal arterioles has never been investigated. In this study, we found that KO of Dusp5 did not alter body weights, kidney and brain weights, plasma glucose, and HbA1C levels. The expression of pERK is higher in the nucleus of primary VSMC isolated from Dusp5 KO rats. Dusp5 KO rats exhibited eutrophic vascular hypotrophy with smaller intracerebral parenchymal arterioles and renal interlobular arterioles without changing the wall‐to‐lumen ratios. These arterioles from Dusp5 KO rats displayed higher myogenic tones, better distensibility, greater compliance, and less stiffness compared with arterioles from WT control rats. VSMC of Dusp5 KO rats exhibited a stronger contractile capability. These results demonstrate, for the first time, that DUSP5 contributes to the regulation of the passive mechanical properties of cerebral and renal arterioles and provide new insights into the role of DUSP5 in vascular function, cancer, stroke, and other cardiovascular diseases.
Clozapine and the Course of Bipolar Disorder in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

Objective: The potential of clozapine in severe bipolar disorder is suggested by its efficacy in refractory schizophrenia, but the evidence is limited thus far. This report utilizes data from the standard care pathway of the Systematic Treatment Enhancement Program to examine the clinical impact of clozapine in bipolar disorder, comparing it to two groups, one that received olanzapine and an additional group that received neither drug. Method: A total of 4,032 outpatients were available for this analysis. Groups for longitudinal analyses are based on the medication used at each visit. Outcomes assessed were clinical status, symptoms subscales, hospitalizations, and death. We utilized mixed models and generalized estimating equations to adjust for baseline differences and investigate longitudinal differences in symptoms, clinical status, and hospitalization rates between groups. Results: During the study, 1.1% (n = 43) of the patients used clozapine at any time. Those on clozapine had significantly fewer manic and depressive symptoms during follow-up as compared with those on neither clozapine nor olanzapine, while those on olanzapine had more symptoms. The use of clozapine was not associated with an increased risk of hospitalization. No deaths were recorded for clozapine group during the trial. Conclusions: Although prescribed to very few patients, the impact of clozapine was notable, with fewer symptoms in patients who had more severe illnesses at baseline. Clozapine could prove to be as successful an intervention for late-stage bipolar disorder as it has been in schizophrenia.
Anterior and posterior hippocampus macro‐ and microstructure across the lifespan in relation to memory—A longitudinal study

There is evidence for a hippocampal long axis anterior–posterior (AP) differentiation in memory processing, which may have implications for the changes in episodic memory performance seen across development and aging. The hippocampus shows substantial structural changes with age, but the lifespan trajectories of hippocampal sub‐regions along the AP axis are not established. The aim of the present study was to test whether the micro‐ and macro‐structural age‐trajectories of the anterior (aHC) and posterior (pHC) hippocampus are different. In a single‐center longitudinal study, 1,790 cognitively healthy participants, 4.1–93.4 years of age, underwent a total of 3,367 MRI examinations and 3,033 memory tests sessions over 1–6 time points, spanning an interval up to 11.1 years. T1‐weighted scans were used to estimate the volume of aHC and pHC (macrostructure), and diffusion tensor imaging to measure mean diffusion (MD, microstructure) within each region. We found that the macro‐ and microstructural lifespan‐trajectories of aHC and pHC were clearly distinguishable, with partly common and partly unique variance shared with age. aHC showed a protracted period of microstructural development, while pHC microstructural development as indexed by MD was more or less completed in early childhood. In contrast, pHC showed larger unique aging‐related changes. An aHC–pHC difference was also observed for volume, with pHC changing relatively more with higher age. All regions showed age‐dependent relationships with episodic memory. aHC micro‐ and macrostructure was significantly related to verbal memory independently of age, but the relationships were still strongest among the older participants. We suggest that memory processes supported by each sub‐region improve or decline in concert with volumetric and microstructural changes in the same age‐period. Future research should disentangle the lifespan relationship between changes in these structural properties and different memory processes, encoding versus retrieval in particular, as well as other cognitive functions depending on the hippocampal long‐axis specialization.
Initial validation of the German version of the Attentional Function Index in a sample of haematological cancer survivors.

OBJECTIVE To date, no German instrument exists to assess subjective levels of cancer-related cognitive impairments (CRCI) in cancer survivors. We translated the validated Attentional Function Index (AFI) into German and explored its psychometric properties. METHODS The validation sample consisted of 1,111 haematological cancer survivors mainly recruited from two cancer registries. Factorial structure was explored using principal component analysis, internal consistency via Cronbach's α, construct validity through correlational analyses (Pearson's r) and associations of patient characteristics with the AFI score via regression analyses. RESULTS In line with the original version, we revealed three factors, that is "effective action" (seven items), "attentional lapses" (three items) and "interpersonal effectiveness" (three items). The overall reliability α was . 91. Verifying construct validity, the AFI score correlated positively with cognitive functioning (r = .64, p ≤ .01) and global QoL (r = .44, p ≤ .01), but negatively with fatigue (r = -.60, p ≤ .01) and depressive symptomatology (r = -.6, p ≤ .01). Older age (β = .12, p < .001), higher comorbidity (β = -.07, p = .02) and being male patient (β = .07, p = .01) were significantly associated with the AFI scores, but effect sizes were small. CONCLUSION The German translation of the AFI shows good psychometric properties and thus may be reasonably applied to measure the subjective level of CRCI in German-speaking oncological populations.
A User-Centered Approach to an Evidence-Based Electronic Health Pain Management Intervention for People With Chronic Pain: Design and Development of EPIO

Background Chronic pain conditions are complicated and challenging to live with. Electronic health (eHealth) interventions show promise in helping people cope with chronic illness, including pain. The success of these interventions depends not only on the technology and intervention content but also on the users’ acceptance and adherence. Involving all stakeholders (eg, patients, spouses, health care providers, designers, software developers, and researchers) and exploring their input and preferences in the design and development process is an important step toward developing meaningful interventions and possibly strengthening treatment outcomes. Objective The aim of this study was to design and develop a user-centered, evidence-based eHealth self-management intervention for people with chronic pain. Methods The study employed a multidisciplinary and user-centered design approach. Overall, 20 stakeholders from the project team (ie, 7 researchers, 5 editors, 7 software developers, and 1 user representative), together with 33 external stakeholders (ie, 12 health care providers, 1 health care manger, 1 eHealth research psychologist, and 17 patients with chronic pain and 2 of their spouses) participated in a user-centered development process that included workshops, intervention content development, and usability testing. Intervention content was developed and finalized based on existing evidence, stakeholder input, and user testing. Stakeholder input was examined through qualitative analyses with rapid and in-depth analysis approaches. Results Analyses from stakeholder input identified themes including a need for reliable, trustworthy, and evidence-based content, personalization, options for feedback, behavioral tracking, and self-assessment/registration as factors to include in the intervention. Evidence-based intervention content development resulted in one face-to-face introduction session and 9 app-based educational and exercise-based modules. Usability testing provided further insight into how to optimize the design of the intervention to the user group, identifying accessibility and a simple design to be essential. Conclusions The design and development process of eHealth interventions should strive to combine well-known evidence-based concepts with stakeholder input. This study, designing and developing the pain management intervention EPIO, illustrates how a stakeholder-centered design approach can provide essential input in the development of an eHealth self-management intervention for people with chronic pain. Trial Registration ClinicalTrials.gov NCT03705104; https://clinicaltrials.gov/ct2/show/NCT03705104
Mycobacterial antigens accumulation in foamy macrophages in murine pulmonary tuberculosis lesions: Association with necrosis and making of cavities

Understanding mechanisms of cavitation in tuberculosis (TB) is the missing link that could advance the field towards better control of the infection. Descriptions of human TB suggest that postprimary TB begins as lipid pneumonia of foamy macrophages that undergoes caseating necrosis and fragmentation to produce cavities. This study aimed to investigate the various mycobacterial antigens accumulating in foamy macrophages and their relation to tissue destruction and necrosis. Pulmonary tissues from mice with slowly progressive TB were studied for histopathology, acid‐fast bacilli (AFB) and presence of mycobacterial antigens. Digital quantification using Aperio ImageScope was done. Until week 12 postinfection, mice were healthy, and lesions were small with scarce AFB and mycobacterial antigens. Colony‐forming units (CFUs) increased exponentially. At week 16‐33, mice were sick, macrophages attained foamy appearance with an increase in antigens (P < .05), 1.5 log increase in CFUs and an approximately onefold increase in AFB. At week 37‐41, mice started dying with a shift in morphology towards necrosis. A >20‐fold increase in mycobacterial antigens was observed with only less than one log increase in CFUs and sevenfold increase in AFB. Secreted antigens were significantly (P < .05) higher compared to cell‐wall antigens throughout infection. Focal areas of necrosis were associated with an approximately 40‐fold increase in antigen MPT46, functionally active thioredoxin, and a significant increase in all secreted antigens. In conclusion, mycobacterial antigens accumulate in the foamy macrophages in TB lesions during slowly progressive murine pulmonary TB. Secreted antigens and MPT46 correlated with necrosis, thereby implying that they might trigger the formation of cavities.
Helicobacter pylori infection status as a prognostic indicator for gastric cancer

Objective To observe the infection status of Helicobacter pylori(HP) in gastric cancer patients and to explore its relationship with the clinical characteristics of gastric cancer.Methods Paraffin sections of surgical specimens from 794 patients who underwent gastrectomy in Changzheng Hosptial or Changhai Hosptial were detected with the modified Giemsa staining to identify the status of HP infection.The association of HP infection status with the clinicopathological features was analyzed by Chi-square test.The relationship between HP infection status and prognosis of gastric patients was analyzed by Kaplan-Meier method and proportional hazard regression model.Results HP infection was significantly associated with Lauren classification,differentiation degree,and lymph-node metastases of gastric cancer(P0.05). The median survival time of the HP positive patients(68.5 months) was significantly longer than that of HP negative patients(36.4 months)(P=0.003). For patients undergoing curative surgeries,those with HP infection had a better prognosis compared with those without HP infection(P=0.034). For patients with intestinal-type gastric cancer,those without HP infection had a poorer prognosis compared with those with HP infection(P=0.006);there were no differences in patients with diffuse-type gastric cancer(P=0.922). Conclusion Our results indicate that HP infection status is not an independent factor for prognosis of gastric cancer patients.HP positive patients with intestinal-type gastric cancer may have a better prognosis.
miR‐873‐3p targets HDAC4 to stimulate matrix metalloproteinase‐13 expression upon parathyroid hormone exposure in rat osteoblasts

Matrix metalloproteinase‐13 (MMP‐13) plays a predominant role in endochondral bone formation and bone remodeling. Parathyroid hormone (PTH) stimulates the expression of MMP‐13 via Runx2, a bone transcription factor in rat osteoblastic cells (UMR106‐01), and histone deacetylase 4 (HDAC4) acts as a corepressor of Runx2. Moreover, microRNAs (miRNAs) play an important role in regulating genes posttranscriptionally. Here, we hypothesized that PTH upregulates the miRNAs targeting HDAC4, which could lead to increased Runx2 activity and MMP‐13 expression in rat osteoblastic cells. We identified several miRNAs that putatively target rat HDAC4 using bioinformatics tools. miR‐873‐3p was significantly upregulated by PTH in rat osteoblasts. miR‐873‐3p overexpression downregulated HDAC4 protein expression, increased Runx2 binding at the MMP‐13 promoter, and increased MMP‐13 messenger RNA expression in UMR106‐01 cells. A luciferase reporter assay identified the direct targeting of miR‐873‐3p at the 3′‐untranslated region of HDAC4. Thus, miR‐873‐3p targeted HDAC4 and relieved the corepressor effect of HDAC4 on Runx2 for MMP‐13 expression in rat osteoblasts. This study advances our knowledge of posttranscriptional gene regulation occurring in bone and bone‐related diseases and clarifies the role of miRNAs as diagnostic biomarkers.
Nerve ultrasound improves detection of treatment-responsive chronic inflammatory neuropathies

Objective To examine the diagnostic accuracy of nerve ultrasound in a prospective cohort of consecutive patients with a clinical suspicion of chronic inflammatory neuropathies, including chronic inflammatory demyelinating polyneuropathy, Lewis-Sumner syndrome, and multifocal motor neuropathy, and to determine the added value in the detection of treatment-responsive patients. Methods Between February 2015 and July 2018, we included 100 consecutive incident patients with a clinical suspicion of chronic inflammatory neuropathy. All patients underwent nerve ultrasound, extensive standardized nerve conduction studies (NCS), and other relevant diagnostic investigations. We evaluated treatment response using predefined criteria. A diagnosis of chronic inflammatory neuropathy was established when NCS were abnormal (fulfilling criteria of demyelination of the European Federation of Neurological Societies/Peripheral Nerve Society) or when the degree of nerve enlargement detected by sonography was compatible with chronic inflammatory neuropathy and there was response to treatment. Results A diagnosis of chronic inflammatory neuropathy was established in 38 patients. Sensitivity and specificity of nerve ultrasound and NCS were 97.4% and 69.4% and 78.9% and 93.5%, respectively. The added value of nerve ultrasound in detection of treatment-responsive chronic inflammatory neuropathy was 21.1% compared to NCS alone. Conclusions Nerve ultrasound and NCS are complementary techniques with superior sensitivity in the former and specificity in the latter. Addition of nerve ultrasound significantly improves the detection of chronic inflammatory neuropathies. Therefore, it deserves a prominent place in the diagnostic workup of chronic inflammatory neuropathies. Classification of evidence This study provides Class IV evidence that nerve ultrasound is an accurate diagnostic tool to detect chronic inflammatory neuropathies.
Evaluating the Effect of Family-Centered Intervention Program on Care Burden and Self-Efficacy of Hemodialysis Patient Caregivers Based on Social Cognitive Theory: A Randomized Clinical Trial Study

Background Caregivers of hemodialysis patients spend a large amount of time providing care to these patients while tolerating fatigue and stress. This study evaluated a family-centered empowerment program on the care burden and self-efficacy of hemodialysis patient caregivers based on social cognitive theory. Methods In this randomized clinical trial, 70 family caregivers of hemodialysis patients in Isfahan, Iran, were selected and randomly allocated to intervention and control groups, in 2015–2016. Two questionnaires were used to collect the family caregivers’ characteristics, care burden, and self-efficacy, and patients’ negative and positive outcomes expectancies. Data were analyzed using SPSS before, immediately after, and 2 months after the intervention. Results There was no significant difference in the mean scores of care burden, positive outcomes expectancies, negative outcomes expectancies, and self-efficacy between the two groups before the intervention. However, there were significant differences in the post-test and follow-up data analyses (P<0.05). Conclusion Given the degenerative nature of chronic kidney disease, it can be considered as a source of long-term and chronic stress for caregivers. Therefore, by implementing an empowerment program, caregiving behaviors can be improved, positive outcomes expectancies can be increased, and negative outcomes expectancies can be reduced.
Eye Vergence Responses During an Attention Task in Adults With ADHD and Clinical Controls

Objective: ADHD patients show poor oculomotor control and recent studies show that attention-related eye vergence is weak in ADHD children. We aimed to assess vergence as a potential diagnostic biomarker for ADHD in adults. Method: We assessed the modulation in the angle of vergence while performing an attention task (N = 144), comparing the results for adults previously diagnosed with ADHD (N = 108) with age-matched clinical controls (N = 36). Results: Significant differences in eye vergence response modulation between clinical controls and ADHD patients were documented. Diagnostic test accuracy was 79%. Conclusion: In combination with an attention task, eye vergence responses could be used as an objective marker to support the clinical diagnosis of adult ADHD.