Miracle-dz/UniFAR-FTUs huggingface dataset:
Clustering and Partitioning of Functional Data for Understanding the Heterogeneity in Psychiatric Diagnosis

In the past two centuries progress has been made in many medical areas with the development of objective tests and understanding of the cause (etiology) and mechanism of diseases (pathophysiology) . Unfortunately, the attempts to understand causes of psychiatric illness by studying genetic or brain functions did not yield the hoped for results and psychiatry still depends on non-objective descriptions of syndromes. Some psychotropic drugs can specifically induce remission, suggesting an experimental approach to understanding the pathophysiological processes. This approach requires evidence that the medication directly affects the disease mechanism, rather than exerting benefit by non-specific compensation. For each particular patient who remits during drug treatment, it is unknown if s/he benefited from a specific pharmacological action or from a non-specific placebo effect or spontaneous remission. If psychiatric illness consists of distinct diagnostic categories (e.g., subjects who’s illness has a mechanism that can be affected by a specific pharmacologic agent, vs. those illness is not affected by this pharmacologic agent), then we should be able to cluster responders to the treatment into distinct classes based on, for example, course of the severity of symptoms over time, medical history and other measures. This would allow to isolate a purer subset of the subjects with more homogeneous response to the drug and, possibly, with similar mechanism of the disease. Importantly, even if there are no distinct diagnostic categories, we will still want to isolate subjects with similar response to the drug, i.e. similar course of symptom decrease over time, in the hopes that homogeneity in the effect of drug on the symptoms reflects analogous pathophysiology. In this paper we describe a strategy for studying the heterogeneity of functional (over time) response to treatment. B-splines are employed to model symptoms’ course over time for dimension reduction of the functional data. Latent mixed effects model [1] is used to test for presence of distinct clusters (diagnostic categories); covariates are used both in the model for the functional measurements and in the latent class model. When there is no evidence for more than one cluster, a parametric k-means and a parametric principal points algorithms are offered for optimal partitioning of the homogeneous distribution of the functional response into K parts [2]. The strategy is applied to functional outcomes from a depression treatment study with the goal of identifying subjects with specific response to the experimental pharmacologic agent.
Vocal Music Therapy for Chronic Pain: A Mixed Methods Feasibility Study

Objective: The purpose of this study was to determine the feasibility and preliminary effects of a vocal music therapy (VMT) program on chronic pain management. Design: A mixed methods intervention design was used in which qualitative data were embedded within a randomized controlled trial. Setting: An urban nurse-management health center on the East Coast of the United States. Subjects: Participants (N = 43) were predominantly Black (79%) and female (76.7%) with an average pain duration of 10 years. Intervention: Participants were randomly allocated to a 12-week VMT program or a waitlist control. Outcome measures: We tracked consent rate (percentage of participants enrolled out of total number screened), attrition rate, and treatment adherence. We used PROMIS® (Patient Reported Outcomes Measurement Information System) tools to measure pain interference, pain-related self-efficacy, pain intensity, depression, anxiety, positive effect, and well-being, ability to participate in social activities, and satisfaction with social roles at baseline and week 12. VMT participants also completed the Patient Global Impression of Change Scale. We conducted semistructured interviews to better understand participants' experience of the intervention. Results: The consent rate was 56%. The attrition rate was 23%. Large treatment effects (partial eta squared) were obtained for self-efficacy (0.20), depression (0.26), and ability to participate in social activities (0.24). Medium effects were found for pain intensity (0.10), anxiety (0.06), positive effect, and well-being (0.06), and small effects for pain interference (0.03) and satisfaction with social roles (0.03). On average, participants felt moderately better after completion of the VMT program (M = 4.93, standard deviation = 1.98). Qualitative findings suggest that VMT resulted in better self-management of pain, enhanced psychological well-being, and stronger social and spiritual connections. Conclusions: Recruitment into the 12-week program was challenging, but quantitative and qualitative findings suggest significant benefits of VMT for chronic pain management.
Automated content analysis across six languages

Corpus selection bias in international relations research presents an epistemological problem: How do we know what we know? Most social science research in the field of text analytics relies on English language corpora, biasing our ability to understand international phenomena. To address the issue of corpus selection bias, we introduce results that suggest that machine translation may be used to address non-English sources. We use human translation and machine translation (Google Translate) on a collection of aligned sentences from United Nations documents extracted from the Multi-UN corpus, analyzed with a “bag of words” analysis tool, Linguistic Inquiry Word Count (LIWC). Overall, the LIWC indices proved relatively stable across machine and human translated sentences. We find that while there are statistically significant differences between the original and translated documents, the effect sizes are relatively small, especially when looking at psychological processes.
Proposed Dynamics of CDB3 Activation in Human Erythrocytes by Nifedipine Studied with Scanning Flow Cytometry

Nifedipine is calcium channels and pumps blocker widely used in medicine. However, mechanisms of nifedipine action in blood are not clear. In particular, the influence of nifedipine on erythrocytes is far from completely understood. In this work, applying scanning flow cytometry, we observed experimentally for the first time the dynamics behind a significant increase of HCO3−/Cl− transmembrane exchange rate of CDB3 (main anion exchanger, AE1, Band 3, SLC4A1) of human erythrocytes in the presence of nifedipine in blood. It was found that the rate of CDB3 activation is not limited by the rate of nifedipine binding and/or Ca2+ transport. In order to explain the experimental data, we suggested a kinetic model assuming that the rate of CDB3 activation is limited by the dynamics of the balance between two intracellular processes (1) the activation of CDB3 limited by its interaction with intracellular Ca2+, and (2) the spontaneous deactivation of CDB3. Thus the use of scanning flow cytometry allowed to clarify quantitatively the molecular kinetic mechanism of nifedipine action on human erythrocytes. In particular, the efficiency (~30) and rates of activation (~0.3 min−1) and deactivation (~10−3 min−1) of CDB3 in human erythrocytes was evaluated for two donors. © 2019 International Society for Advancement of Cytometry
Cytoplasmic Parvovirus Capsids Recruit Importin Beta for Nuclear Delivery

Parvoviruses are small DNA viruses that deliver their DNA into the postmitotic nuclei, which is an important step for parvoviral gene and cancer therapies. Limitations in virus-receptor interactions or endocytic entry do not fully explain the low transduction/infection efficiency, indicating a bottleneck after virus entry into the cytoplasm. We thus investigated the transfer of parvovirus capsids from the cytoplasm to the nucleus, showing that the nuclear import of the parvovirus capsid follows a unique strategy, which differs from classical nuclear import and those of other viruses. ABSTRACT Parvoviruses are an important platform for gene and cancer therapy. Their cell entry and the following steps, including nuclear import, are inefficient, limiting their use in therapeutic applications. Two models exist on parvoviral nuclear entry: the classical import of the viral capsid using nuclear transport receptors of the importin (karyopherin) family or the direct attachment of the capsid to the nuclear pore complex leading to the local disintegration of the nuclear envelope. Here, by laser scanning confocal microscopy and in situ proximity ligation analyses combined with coimmunoprecipitation, we show that infection requires importin β-mediated access to the nuclear pore complex and nucleoporin 153-mediated interactions on the nuclear side. The importin β-capsid interaction continued within the nucleoplasm, which suggests a mixed model of nuclear entry in which the classical nuclear import across the nuclear pore complex is accompanied by transient ruptures of the nuclear envelope, also allowing the passive entry of importin β-capsid complexes into the nucleus. IMPORTANCE Parvoviruses are small DNA viruses that deliver their DNA into the postmitotic nuclei, which is an important step for parvoviral gene and cancer therapies. Limitations in virus-receptor interactions or endocytic entry do not fully explain the low transduction/infection efficiency, indicating a bottleneck after virus entry into the cytoplasm. We thus investigated the transfer of parvovirus capsids from the cytoplasm to the nucleus, showing that the nuclear import of the parvovirus capsid follows a unique strategy, which differs from classical nuclear import and those of other viruses.
The ox atrioventricular conduction axis compared to human in relation to the original investigation of sunao tawara

It was Sunao Tawara who, in 1906, established the foundations for knowledge of the arrangement of the atrioventricular conduction axis in man and other mammals. Study of the hearts of ungulates was a central part in his investigation, which assessed other species, including man. He described several subtle differences between the mammals. We have now ourselves studied the cardiac conduction tissue of the ox heart, comparing our findings with our knowledge of the arrangement in man, and providing new insights into the differences illustrated by Tawara. It is, perhaps, surprising that these differences, although subtle, have not attracted more attention. We show that the major difference is the fact that the noncoronary aortic sinus in the ox heart is mainly supported by the myocardium of the ventricular septum, whereas in the human heart the sinus, and its leaflet, are in fibrous contiguity with the aortic leaflet of the mitral valve. It is this feature that determines the difference in the arrangement of the conduction axis between the species. We also show that the emergence of the left bundle branch on the left ventricular aspect of the muscular septum is more variable than previously described. Clin. Anat. 33:383–393, 2020. © 2019 Wiley Periodicals, Inc.
Anatomy and White Matter Connections of the Superior Frontal Gyrus.

INTRODUCTION The superior frontal gyrus (SFG) is an important region implicated in a variety of tasks including motor movement, working memory, resting-state and cognitive control. A detailed understanding of the subcortical white matter of the SFG could improve post-operative morbidity related to surgery around this gyrus. Through DSI-based fiber tractography validated by gross anatomical dissection, we characterized the fiber tracts of the SFG based on their relationships to other well-known neuroanatomic structures. MATERIALS AND METHODS Diffusion imaging from the Human Connectome Project from ten healthy adult subjects was used for fiber tractography. We evaluated the SFG as a whole based on its connectivity with other regions. All tracts were mapped in both hemispheres, and a lateralization index was calculated based on resultant tract volumes. Ten cadaveric dissections were then performed using a modified Klingler technique to delineate the location of major tracts integrated within the SFG. RESULTS We identified four major SFG connections: the frontal aslant tract connecting to the inferior frontal gyrus; the inferior fronto-occipital fasciculus connecting to the cuneus, lingual gyrus, and superior parietal lobule; the cingulum connecting to the precuneus and parahippocampal gyrus/uncus; and a callosal fiber bundle connecting the SFG bilaterally. CONCLUSIONS The functional networks of the SFG involve a complex series of white matter tracts integrated within the gyrus, including the FAT, IFOF, cingulum, and callosal fibers. Post-surgical outcomes related to this region may be better understood in the context of the fiber-bundle anatomy highlighted in this study This article is protected by copyright. All rights reserved.
The exercise cytokine interleukin-15 rescues slow wound healing in aged mice

Impaired wound healing in elderly individuals increases infection risk and prolongs surgical recovery, but current treatment options are limited. Low doses of interleukin-15 (IL-15) that mimic exercise responses in the circulation improve skin structure and increase mitochondria in uninjured aged skin, suggesting that IL-15 is an essential mitochondrial signal for healing that is lost during aging. Here we used gene microarray analysis of old and young murine epidermal stem cells and demonstrate that aging results in a gene signature characteristic of bioenergetic dysfunction. Intravenous IL-15 treatment rescued chronological aging-induced healing defects and restored youthful wound closure in old, sedentary mice. Additionally, exercise-mediated improvements in the healing of aged skin depend upon circulating IL-15. We show that IL-15 induces signal transducer and activator of transcription 3 (STAT3) signaling characteristic of young animals, reduces markers of growth arrest, and increases keratinocyte and fibroblast growth. Moreover, exercise or exercise-mimicking IL-15 treatment rescued the age-associated decrease in epidermal mitochondrial complex IV activity. Overall, these results indicate that IL-15 or its analogs represent promising therapies for treating impaired wound healing in elderly patients.
Processivity in Bacterial Glycosyltransferases

Extracellular polysaccharides and glycoproteins of pathogenic bacteria assist in adherence, autoaggregation, biofilm formation, and host immune system evasion. As a result, considerable research in the field of glycobiology is dedicated to study the composition and function of glycans associated with virulence, as well as the enzymes involved in their biosynthesis with the aim to identify novel antibiotic targets. Especially, insights into the enzyme mechanism, substrate binding, and transition-state structures are valuable as a starting point for rational inhibitor design. An intriguing aspect of enzymes that generate or process polysaccharides and glycoproteins is the level of processivity. The existence of enzymatic processivity reflects the need for regulation of the final glycan/glycoprotein length and structure, depending on the role they perform. In this Review, we describe the currently reported examples of various processive enzymes involved in polymerization and transfer of sugar moieties, predominantly in bacterial pathogens, with a focus on the biochemical methods, to showcase the importance of studying processivity for understanding the mechanism.
Down-regulation of ATAD2 restrains cancer stem cell properties in esophageal squamous cell carcinoma via blockade of the Hedgehog signaling pathway.

Esophageal squamous cell carcinoma (ESCC) ranks among the five most common cancers in China, and has a five-year survival rate of less than 15%. The transcription factor ATAD2 has potential as a therapeutic target in various tumors, and microarray-based gene expression profiling reveals dysregulation of ATAD2 specifically in ESCC. Here we investigated whether ATAD2 could mediate a regulation of cancer stem cell (CSC) biological functions in ESCC. Immunohistochemical staining, reverse transcription quantitative polymerase chain reaction, and Western blot assays all revealed up-regulation of ATAD2 in ESCC tissues and cell lines, which furthermore correlated with progression of ESCC. In loss-of-function experiments, silencing of ATAD2 inhibited activation of the Hedgehog signaling pathway, as indicated by reduced expression of Gli1, SMO, and PTCH1. Investigations with EdU, Transwell assay, scratch test, flow cytometry and colony formation assay showed that silencing of ATAD2 or inhibiting the Hedgehog signaling decreased the proliferation, invasion and migration abilities along with colony formation, but elevated the apoptosis rate of CSCs. Further, in vivo experiments validated the suppressive effect of siRNA-mediated ATAD2 silencing on tumor growth in nude mice. Thus, down-regulation of ATAD2 can seemingly restrain the malignant phenotypes of ESCC cells through inhibition of the Hedgehog signaling pathway.
On the ethics of algorithmic decision-making in healthcare

In recent years, a plethora of high-profile scientific publications has been reporting about machine learning algorithms outperforming clinicians in medical diagnosis or treatment recommendations. This has spiked interest in deploying relevant algorithms with the aim of enhancing decision-making in healthcare. In this paper, we argue that instead of straightforwardly enhancing the decision-making capabilities of clinicians and healthcare institutions, deploying machines learning algorithms entails trade-offs at the epistemic and the normative level. Whereas involving machine learning might improve the accuracy of medical diagnosis, it comes at the expense of opacity when trying to assess the reliability of given diagnosis. Drawing on literature in social epistemology and moral responsibility, we argue that the uncertainty in question potentially undermines the epistemic authority of clinicians. Furthermore, we elucidate potential pitfalls of involving machine learning in healthcare with respect to paternalism, moral responsibility and fairness. At last, we discuss how the deployment of machine learning algorithms might shift the evidentiary norms of medical diagnosis. In this regard, we hope to lay the grounds for further ethical reflection of the opportunities and pitfalls of machine learning for enhancing decision-making in healthcare.
in Human Lung Cancer Cells

Previously, we have shown that opioids ading via specific receptors inhibit the growth of human lung cancer cells while nicotine, ading through nicotinic acetylcholine receptors, reverses this inhibition. Therefore, we studied the role of apoptosis in these processes. Treatment of human lung cancer cells with 0.1-1 �M morphine or methadone resulted in morphological changes and cleavage of DNA into
A Pioneer in Psychotherapy Research: Aaron Beck

SB: I gather you grew up in a Jewish family, your parents having migrated to the United States from Russia. What was it like for you? Did that experience influence you in choosing to study medicine? AB: I grew up with loving parents, which was a problem when I was in psychoanalysis; I could not recall any unpleasant experiences in growing up. I was the youngest of three siblings. My parents actually lost two children before I was born. A sister died in the influenza epidemic of 1920, and in a way I was a replacement for her. If anything, my mother was very over-protective. The most traumatic episode in my childhood was when I broke my arm and developed septicaemia. At one point they were thinking of amputating my arm, but then thought that it wouldn’t work. I learnt years later that it was a staphylococcus infection which had about 95% mortality in those days. Obviously I recovered and still retained my arm but the impact on me psychologically was that I developed an intense fear of surgery and a blood injury phobia. For many years if I saw anything related to surgery or to injury, I would become faint and occasionally I almost toppled over. One of my ambitions was to overcome this fear. I did so eventually through exposure and willpower. When I went to medical school I often experienced feelings of faintness but I would go to the operating room to desensitize myself. Eventually I was able to overcome the problem. This may have been one of the roots of my later thinking that it was possible to overcome very disabling symptoms. SB: You could have gone another route and concluded: ‘Medicine is not for me; I am one of the faint-hearted’. Did you think this through or was it an unconsciously determined decision? AB: Everything is retrospective. I tended to face and meet challenges throughout my childhood and adolescence. The greatest learning experience I ever had probably though was as a Boy Scout. I had to learn things that were quite difficult for me – lifesaving, swimming half a mile, and things of that nature. I think that if there was any pattern in my life it was going out and meeting challenges that lay before me. I think I was conscious of that and I would galvanize myself. I had a strong need to conquer whatever problems I faced.
Site Quality, Disturbance, and Vegetation Effects on Carbon Storage and Accumulation in Old, Mixed-Species Stands in Central Maine, USA

ABSTRACT Carbon (C) storage and accumulation in forests is of growing importance as climate change focuses our attention on rising greenhouse gas emissions. In 2012, we measured total ecosystem C pools (including live vegetation, dead wood, and soils) in two unmanaged, mixed-species stands in central Maine, USA. The stands are adjacent to one another and serve as references against which silvicultural treatments can be compared. The soil parent material of the stands was different (marine sediments versus glacial till), which provided an ideal opportunity to compare C stocks between these stands. We used tree ring analysis and repeated forest inventories to estimate tree and dead wood recruitment patterns and past disturbance severity. Site quality influenced C trajectories through its influence on tree species composition, which in turn strongly determined stand susceptibility to insect outbreaks. In 2012, total ecosystem C stocks were 196.3 ± 9.6 Mg ha–1 (mean ± SD) in the stand on soils derived from marine sediments and 247.0 ± 17.7 Mg ha–1 in the stand on soils derived from glacial till. Differences in average total ecosystem C stocks were primarily driven by the live tree C pool. Despite the occurrence of several partial disturbance events from 1954 to 2012, live tree C stocks increased over time in both stands. Average C accumulation in recruited dead wood was also positive, indicating that aboveground biomass served as a C sink. Our results can be used to inform decisions related to C objectives in unmanaged stands of similar species composition and soils.
Total hip arthroplasty planning

Preoperative planning is mandatory to achieve the restoration of a correct and personalized biomechanics of the hip. The radiographic review is the first and fundamental step in the planning. Limb or pelvis malpositioning during the review results in mislead planning. Correct templating is possible using three different methods: acetate templating on digital X-ray, digital 2D templating on digital X-ray and 3D digital templating on CT scan. Time efficiency, costs, reproducibility and accuracy must be considered when comparing different templating methods. Based on these parameters, acetate templating should not be abandoned; digital templating allows a permanent record of planning and can be electronically viewed by different members of surgical team; 3D templating is intrinsically more accurate. There is no evidence in the few recently published studies that 3D templating impacts positively on clinical outcomes except in difficult cases. The transverse acetabular ligament (TAL) is a reliable intraoperative soft tissue reference to set cup position. Spine–hip relations in osteoarthritic patients undergoing hip joint replacement must be considered. Cite this article: EFORT Open Rev 2019;4:626-632. DOI: 10.1302/2058-5241.4. 180075