Miracle-dz/UniFAR-FTUs huggingface dataset:
Osteoanabolic Agents for Osteoporosis

Abstract Medications for osteoporosis are classified as either antiresorptive or anabolic. Whereas antiresorptive agents prevent bone resorption, anabolic agents promote new bone formation. Anabolics should be considered in individuals with severe osteoporosis, failure of alternative osteoporosis agents, intolerability or contraindications to other osteoporosis agents, and glucocorticoid-induced osteoporosis. There are currently two approved anabolic therapies, teriparatide and abaloparatide, and a third anabolic agent, romozosumab, is under review by the US Food and Drug Administration. Teriparatide and abaloparatide are administered as daily subcutaneous injections and have been shown to reduce vertebral and nonvertebral fractures significantly. The most common side effects are headache and nausea, but teriparatide and abaloparatide are generally well tolerated. The sequence of administration of anabolic therapy is important. Benefits of anabolics are attenuated in individuals with prior antiresorptive exposure; however, antiresorptive agents administered after anabolics consolidate bone mineral density gains.
Beyond Telnet: Prevalence of IoT Protocols in Telescope and Honeypot Measurements

With the arrival of the Internet of Things (IoT), more devices appear online with default credentials or lacking proper security protocols. Consequently, we have seen a rise of powerful DDoS attacks originating from IoT devices in the last years. In most cases the devices were infected by bot malware through the telnet protocol. This has lead to several honeypot studies on telnet-based attacks. However, IoT installations also involve other protocols, for example for Machine-to-Machine communication. Those protocols often provide by default only little security. In this paper, we present a measurement study on attacks against or based on those protocols. To this end, we use data obtained from a /15 network telescope and three honey-pots with 15 IPv4 addresses. We find that telnet-based malware is still widely used and that infected devices are employed not only for DDoS attacks but also for crypto-currency mining. We also see, although at a much lesser frequency, that attackers are looking for IoT-specific services using MQTT, CoAP, UPnP, and HNAP, and that they target vulnerabilities of routers and cameras with HTTP.
3D modeling for augmented reality systems in novel vascular models

Endovascular surgery is a continually developing branch of vascular surgery where the therapeutic intervention is performed from within the lumen of the vessel, usually under X-ray guidance. When the major artery of the body (aorta) becomes swollen (aneurysm), there is a danger of rupture, leading to catastrophic blood loss and death. An essential part of the procedure is preoperative planning, taking accurate measurements of both the diameter and the length of the area to be excluded. There is no freely available, reliable, realistic simulator on which either the trainee can practice index cases or where trained surgeons can simulate more complex cases before they are performed on the patient. VR is developing and becoming more and more accessible. To be able to make the most of these tools we will explore the feasibility of using them for creating a 3D model of the aorta on which training can be carried out.
Association Between Purpose in Life and Glucose Control Among Older Adults.

Background Greater purpose in life is associated with lower rates of certain chronic diseases. Whether purpose in life can protect against development of prediabetes or type 2 diabetes is unknown. Purpose To examine the association between purpose in life and blood glucose control among adults ≥50 years. Methods We conducted a longitudinal cohort study of 3,907 participants of the Health and Retirement Study who at baseline did not have type 2 diabetes or prediabetes. Baseline purpose in life was measured using the Ryff and Keyes' Scales of Psychological Well-Being and grouped into tertiles (high, medium, and low). We used multivariable linear regression to examine the association between baseline purpose in life and HbA1c over 4 years. Multivariable logistic regression was used to examine the association between baseline purpose and incident prediabetes or type 2 diabetes over the same period. Results After adjusting for sociodemographic factors, body mass index, physical activity, and physical and mental health factors, HbA1c was 0.07 percentage points lower among participants with high purpose than those with low purpose (95% confidence interval [CI] -0.12 to -0.02; p = .011). Participants with high purpose had lower odds of developing prediabetes or type 2 diabetes than those with low purpose (adjusted odds ratio 0.78; 95% CI 0.62 to 0.98; p = .037). Conclusions Among older adults, greater purpose in life is associated with a lower incidence of prediabetes or type 2 diabetes. Strategies to promote greater purpose in life should be tested as a part of type 2 diabetes prevention efforts.
The role of OPRM1 polymorphism in the etiology of alcoholism.

BACKGROUND Numerous studies have investigated the association between the OPRM1 A118G polymorphism (rs1799971) and alcohol dependence, but the results have been inconsistent. The endogenous opioid system has been implicated in the development of alcohol dependence for its prominent role in the central rewarding mechanism. OBJECTIVES The aim of this study was to evaluate the role of the A118G polymorphism of the OPRM1 gene in the pathogenesis of alcohol dependence syndrome (ADS). MATERIAL AND METHODS The OPRM1 (rs1799971) polymorphism was investigated in an association study of a group of ADS patients (n = 177) and in subgroups (delirium tremens and/or seizures, age at onset <26 years, dissocial alcoholics, positive familial history of alcoholism, delirium tremens, and seizures). The control group consisted of healthy volunteers, with matched gender and age, and with psychiatric disorders excluded (n = 162). RESULTS Our research shows that there are differences in the genotypes and alleles of the OPRM1 polymorphism in the case-control study. Furthermore, we observed associations in our homogeneous subgroups - in the group of patients with ADS and accompanying delirium tremens and/or seizures at the genotype level, as well as in the subgroup of patients under 26 years of age with an early onset of dependence. CONCLUSIONS It is strongly possible that the G allele described in numerous studies can be associated with a response to treatment, but not typology, or the very predisposition toward alcoholism. It is necessary to carry out further research which would embrace a larger group of patients; it should be divided into other homogeneous subgroups, including, e.g., naltrexone pharmacotherapy.
The role of grouping in sketched diagram recognition

An early step in bottom-up diagram recognition systems is grouping ink strokes into shapes. This paper gives an overview of the key literature on automatic grouping techniques in sketch recognition. In addition, we identify the major challenges in grouping ink into identifiable shapes, discuss the common solutions to these challenges based on current research, and highlight areas for future work.
Association Between Primary Hypothyroidism and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

BACKGROUND It is currently uncertain whether primary hypothyroidism is associated with nonalcoholic fatty liver disease (NAFLD). We performed a meta-analysis of relevant studies to quantify the magnitude of association between primary hypothyroidism and risk of NAFLD. METHODS We searched PubMed, Web of Science and Scopus databases from January 2000 to March 2018 using predefined keywords to identify observational cross-sectional, case-control, and longitudinal studies in which NAFLD was diagnosed by imaging or biopsy. Data from selected studies were extracted and meta-analysis was performed using random-effects modeling. RESULTS A total of 12 cross-sectional and 3 longitudinal studies enrolling 44,140 individuals were included in the final analysis. Hypothyroidism (defined either by self-reported history of hypothyroidism with use of levothyroxine replacement therapy or by presence of abnormal thyroid function tests) was associated with an increased risk of prevalent NAFLD (n = 12 studies; random-effects odds ratio 1.42 [95% confidence interval (CI) 1.15-1.77]; I2 = 51.2%), independently of age, sex, body mass index and other common metabolic risk factors. The magnitude of risk paralleled the underlying severity of NAFLD histology (n = 3 studies; random-effects odds ratio 2.73 [CI 1.90-3.93]; I2 = 0%), and tended to increase across the different definitions used for diagnosing hypothyroidism. Meta-analysis of data from the three longitudinal studies showed that subclinical hypothyroidism was not independently associated with risk of incident ultrasound-defined NAFLD over a median of 5 years (random-effects hazard ratio 1.29 [CI 0.89-1.86]; I2 = 83.9%). Sensitivity analyses did not alter these findings. Funnel plot did not reveal significant publication bias. CONCLUSIONS This large and updated meta-analysis shows that the presence of variably defined hypothyroidism is significantly associated with the presence and severity of NAFLD. However, the observational design of the eligible studies does not allow for proving causality.
Set4 is a chromatin-associated protein, promotes survival during oxidative stress, and regulates stress response genes in yeast

The Set4 protein in the yeast Saccharomyces cerevisiae contains both a PHD finger and a SET domain, a common signature of chromatin-associated proteins, and shares sequence homology with the yeast protein Set3, the fly protein UpSET, and the human protein mixed-lineage leukemia 5 (MLL5). However, the biological role for Set4 and its potential function in chromatin regulation has not been well defined. Here, we analyzed yeast cell phenotypes associated with loss of Set4 or its overexpression, which revealed that Set4 protects against oxidative stress induced by hydrogen peroxide. Gene expression analysis indicated that Set4 promotes the activation of stress response genes in the presence of oxidative insults. Using ChIP analysis and other biochemical assays, we also found that Set4 interacts with chromatin and directly localizes to stress response genes upon oxidative stress. However, recombinant Set4 did not show detectable methyltransferase activity on histones. Our findings also suggest that Set4 abundance in the cell is balanced under normal and stress conditions to promote survival. Overall, these results suggest a model in which Set4 is a stress-responsive, chromatin-associated protein that activates gene expression programs required for cellular protection against oxidative stress. This work advances our understanding of mechanisms that protect cells during oxidative stress and further defines the role of the Set3–Set4 subfamily of SET domain–containing proteins in controlling gene expression in response to adverse environmental conditions.
Jones Fractures Identified at the National Football League Scouting Combine: Assessment of Prognostic Factors, Computed Tomography Findings, and Initial Career Performance

Background: Jones fractures result in subsequent dysfunction and remain an issue for athletes. Purpose: To (1) describe the epidemiology, treatment, and impact of Jones fractures identified at the National Football League (NFL) Scouting Combine on players’ early careers and (2) establish the value of computed tomography (CT) to determine bony healing after a fracture in prospective players. Study Design: Cohort study; Level of evidence, 3. Methods: All players who attended the combine between 2009 and 2015 were retrospectively reviewed to identify their history of Jones fractures. The playing position, treatment method, and number of missed collegiate games were recorded. The mean overall draft pick number, number of games started and played, snap percentage, and position-specific performance scores (fantasy score) over the first 2 years in the NFL were compared between players with fractures and controls. An imaging classification system was applied based on grading of each quadrant of the fifth metatarsal (plantar, dorsal, medial, lateral), with a score of 0 for not healed or 1 for healed. Results: Overall, the number of Jones fractures identified was 72 in 2285 athletes (3.2%), with all treated via intramedullary screw fixation. The mean overall draft pick number for players with fractures was 111.2 ± 67.9 compared with 99.0 ± 65.9 for controls (P = .12). Performance scores for players with fractures were lower than those for controls across all positions, with a significant difference in running backs (2.6 vs 4.0, respectively; P < .001) and defensive linemen (1.4 vs 2.3, respectively; P = .02). The mean CT score was 2.5 ± 1.3. Of the 32 athletes who underwent imaging, 16 Jones fractures (50.0%) were healed or nearly healed, 12 (37.5%) were partially healed, and 4 (12.5%) showed little or no healing. The plantar cortex demonstrated the least healing (18/32; 56.3%), followed by the lateral cortex (15/32; 46.9%). Players with a mean score <1 were found to have fewer games started (2.7 ± 2.5) than those with 1 to 3 cortices healed (17.4 ± 10.4) or all cortices healed (8.7 ± 11.2). Conclusion: Based on CT, 50% of all players with a previous Jones fracture demonstrated incomplete healing. Moreover, position-specific performance scores over the first 2 years of a player’s career were lower across all positions for those with fractures compared with controls. Players with CT scores <1 were found to start fewer games and were drafted later than controls.
Combination of Suicide and Cytokine Gene Therapies as Surgery Adjuvant for Canine Mammary Carcinoma

The incidence of canine mammary carcinoma varies with age, breed, and spay status, being among the main tumors appearing in intact female dogs. Thirty-six canine mammary carcinoma patients received injections of canine interferon-β (cIFN-β) and HSV-thymidine kinase/ganciclovir (HSV-tk/GCV) carrying lipoplexes, into the tumor bed, immediately after surgery. Next, they started periodic subcutaneous injections of lipoplexes carrying a human granulocyte-macrophage colony stimulating factor and interleukin-2 mixed with allogeneic mammary carcinoma extracts. This combined strategy was safe and well tolerated. In addition, only two out of 26 patients treated with complete surgery developed a local relapse, and 0 out of 29 stage II and III patients displayed distant metastases, suggesting both local and systemic antitumor activities. The most encouraging result was the long survival times: 22 > 1 year (where 13 > 2 and 4 > 3 years), while maintaining a good quality of life. The preliminary results in five patients presenting with local disease, an additional HSV-tk/GCV plus cIFN-β gene treatment induced local antitumor activity, evidenced by four objective responses (one complete, three partial) and one stable disease. This successful outcome supports further studies to validate this approach not only for canine veterinary patients, but also for translation to human patients.
Hospital purchasing alliances: Ten years after.

BACKGROUND Most hospitals outsource supply procurement to purchasing alliances, or group purchasing organizations (GPOs). Despite their early 20th century origin, we lack both national and trend data on alliance utilization, services, and performance. The topic is important as alliances help hospitals control costs, enjoy tailwinds from affiliated regional/local alliances, and face headwinds from hospital self-contracting and criticism of certain business practices. PURPOSE We compare the utilization, services, and performance of alliances in 2004 and 2014. APPROACH We analyze alliances using two comparable surveys of hospitals. We use significance tests to assess changes in alliance utilization, services, and performance (e.g., cost savings). We also assess the use of regional/local alliances affiliated with national GPOs. RESULTS Purchasing through national alliances has somewhat diminished. Over 10 years, hospitals have diversified GPO memberships to include regional/local alliances (many affiliated with their national GPO) and engaged in self-contracting. At the same time, hospitals have increased purchases of many categories of supplies/services through national GPOs and endorsed their value-added functions and increasingly important role. Hospitals report greater satisfaction with several GPO functions; performance on most dimensions has not changed. CONCLUSIONS National alliances still play important roles that hospitals find valuable. PRACTICE IMPLICATIONS Purchasing alliances continue to play an important role in helping hospitals with both cost savings and new services. Their growing complexity, along with growing use of self-contracting, poses managerial challenges for hospital purchasing staff that may require greater hospital investment.
Joint Rate and FoV adaptation in immersive video streaming

The responsiveness of the network is critical when the application is immersive video streaming or 360 degree video streaming. The users look at the video stream on a display that can only show a fraction of the full video stream, and the time that the information spend in transit dramatically impacts the QoE of the end user. Further, transmitting a 360 degree video stream significantly increases the bandwidth usage and the impact on the already strained network. We propose a mechanism to use the responsiveness of the network to perform a Field of View (FoV) adaptation, so as to reduce the bandwidth consumption while at the same time enhancing the QoE of the user. In our simulation, such mechanism significantly improves the resolution seen by the end user, by selecting a higher bit rate. This translates to an improvement of up to 1.34 x better resolution when compared with the full spherical 360 degree video stream. Further, when rate adaption is used, it ensures the QoE of end users evolves according to the changes in the network conditions. This means that our proposed rate and FoV adaptation based upon the network responsiveness achieves both the apprently contradictory goals of increasing the end-user QoE and reducing the overall bandwidth consumption at the network layer.
Robustness of Spike Deconvolution for Neuronal Calcium Imaging

Calcium imaging is a powerful method to record the activity of neural populations in many species, but inferring spike times from calcium signals is a challenging problem. We compared multiple approaches using multiple datasets with ground truth electrophysiology and found that simple non-negative deconvolution (NND) outperformed all other algorithms on out-of-sample test data. We introduce a novel benchmark applicable to recordings without electrophysiological ground truth, based on the correlation of responses to two stimulus repeats, and used this to show that unconstrained NND also outperformed the other algorithms when run on “zoomed out” datasets of ∼10,000 cell recordings from the visual cortex of mice of either sex. Finally, we show that NND-based methods match the performance of a supervised method based on convolutional neural networks while avoiding some of the biases of such methods, and at much faster running times. We therefore recommend that spikes be inferred from calcium traces using simple NND because of its simplicity, efficiency, and accuracy. SIGNIFICANCE STATEMENT The experimental method that currently allows for recordings of the largest numbers of cells simultaneously is two-photon calcium imaging. However, use of this powerful method requires that neuronal firing times be inferred correctly from the large resulting datasets. Previous studies have claimed that complex supervised learning algorithms outperform simple deconvolution methods at this task. Unfortunately, these studies suffered from several problems and biases. When we repeated the analysis, using the same data and correcting these problems, we found that simpler spike inference methods perform better. Even more importantly, we found that supervised learning methods can introduce artifactual structure into spike trains, which can in turn lead to erroneous scientific conclusions. Of the algorithms we evaluated, we found that an extremely simple method performed best in all circumstances tested, was much faster to run, and was insensitive to parameter choices, making incorrect scientific conclusions much less likely.
Towards a More Reliable Store-and-forward Protocol for Mobile Text Messages

Businesses often use mobile text messages (SMS) as a cost effective and universal way of communicating concise information to their customers. Today, these messages are usually sent via SMS brokers, which forward them further to the next stakeholder, typically the various mobile operators, and then the messages eventually reach the intended recipients. Infoflex Connect AB delivers an SMS gateway application to the brokers with the main responsibility of reliable message delivery within set quality thresholds. However, the protocols used for SMS communication are not designed for reliability and thus messages may be lost. In this position paper we deduce requirements for a new protocol for routing messages through the SMS gateway application running at a set of broker nodes, in order to increase the reliability. The requirements cover important topics for the required communication protocol such as event ordering, message handling and system membership. The specification of such requirements sets the foundation for the forthcoming design and implementation of such a protocol and its evaluation.
The Potential of CRISPR/Cas9 Gene Editing as a Treatment Strategy for Alzheimer’s Disease

Despite a wealth of knowledge gained in the past three decades concerning the molecular underpinnings of Alzheimer’s disease (AD), progress towards obtaining effective, disease modifying therapies has proven to be challenging. In this manner, numerous clinical trials targeting the production, aggregation, and toxicity of beta-amyloid, have failed to meet efficacy standards. This puts into question the beta-amyloid hypothesis and suggests that additional treatment strategies should be explored. The recent emergence of CRISPR/Cas9 gene editing as a relatively straightforward, inexpensive, and precise system has led to an increased interest of applying this technique in AD. CRISPR/Cas9 gene editing can be used as a direct treatment approach or to help establish better animal models that more faithfully mimic human neurodegenerative diseases. In this manner, this technique has already shown promise in other neurological disorders, such as Huntington’s disease. The purpose of this review is to examine the potential utility of CRISPR/Cas9 as a treatment option for AD by targeting specific genes including those that cause early-onset AD, as well as those that are significant risk factors for late-onset AD such as the apolipoprotein E4 (APOE4) gene.
Improving TCP Congestion Control with Machine Intelligence

In a TCP/IP network, a key to ensure efficient and fair sharing of network resources among its users is the TCP congestion control (CC) scheme. Previously, the design of TCP CC schemes is based on hard-wiring of predefined actions to specific feedback signals from the network. However, as networks become more complex and dynamic, it becomes harder to design the optimal feedback-action mapping. Recently, learning-based TCP CC schemes have attracted much attention due to their strong capabilities to learn the actions from interacting with the network. In this paper, we design two learning-based TCP CC schemes for wired networks with under-buffered bottleneck links, a loss predictor (LP) based TCP CC (LP-TCP), and a reinforcement learning (RL) based TCP CC (RL-TCP). We implement both LP-TCP and RL-TCP in NS2. Compared to the existing NewReno and Q-learning based TCP, LP-TCP and RL-TCP both achieve a better tradeoff between throughput and delay, under various simulated network scenarios.