Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity

Abstract Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic–pituitary–adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism’s response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic–pituitary–gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.
Effectiveness of patiromer in the treatment of hyperkalemia in chronic kidney disease patients with hypertension on diuretics

Objective: Recurrent hyperkalemia frequently limits use of renin–angiotensin–aldosterone system inhibitors (RAASi) in chronic kidney disease (CKD) patients with hypertension, diabetes, and/or heart failure. Patiromer is a sodium-free, nonabsorbed potassium (K+)-binding polymer approved by the US Food and Drug Administration for the treatment of hyperkalemia. This post-hoc analysis of OPAL-HK examined the effectiveness and safety of patiromer in reducing serum K+ in hyperkalemic CKD patients on RAASi, with hypertension, receiving diuretic therapy versus those not on diuretics. Methods: Depending on the degree of hyperkalemia at baseline, CKD patients with serum K+ from 5.1 to less than 6.5 mmol/l on RAASi (n = 243) were assigned to a patiromer of total dose 8.4 or 16.8 g, divided twice daily. Changes in serum K+, and tolerability and safety were assessed over 4 weeks in patients on and not on diuretics. Results: At baseline, 132 patients used diuretics and 111 were not on diuretics, mean age was 64.3 and 64.0 years, respectively, and 63 and 51% were men. Similar reductions in serum K+ were seen over 4 weeks in both subgroups. At week 4, serum K+ fell by −0.95 ± 0.04 mmol/l with any diuretic and −1.04 ± 0.05 mmol/l with no diuretic. Patiromer was well tolerated, with mild-to-moderate constipation reported as the most common adverse event (7.6 and 14.4% of patients on any diuretic or no diuretic, respectively). Hypokalemia (s-K+ <3.5 mEq/l) was reported in 2.3% of patients on any diuretic and in 3.7% not on diuretics. Conclusion: The serum K+-lowering efficacy and safety profile of patiromer in hyperkalemia patients with CKD was not compromised by diuretic therapy.
SYNTHESIS, EXPERIMENTAL CHARACTERIZATION AND PARAMETRIC IDENTIFICATION OF IONIC-POLYMER METAL COMPOSITE BENDING ACTUATORS

Ionic polymer metal composite (IPMC) actuator is a sandwiched structure with a thin polyelectrolyte strip or membrane plated with metal electrodes on both sides. Under a low applied voltage the IPMC strip bends toward either electrode depending on its polarity, forming a soft actuator for potential diverse applications. We report in details our methodologies for synthesizing IPMC with high quality electrode morphologies. We describe our experimental setup for measuring the physical and mechanical properties of IPMC. In conjunction with the experimental characterization, we finally present a parameter identification scheme to identify two key parameters for establishing relationship between unbalanced charge density and the associated electrostatic eigenstress, a constitutive law widely used in IPMC literature. The experimental and simulation procedures presented herein pave the avenue for fabrication, characterization and development of novel IPMC-based sensors and actuators.
Hippocampus‐associated causal network of structural covariance measuring structural damage progression in temporal lobe epilepsy

In mesial temporal lobe epilepsy (mTLE), the causal relationship of morphometric alterations between hippocampus and the other regions, that is, how the hippocampal atrophy leads to progressive morphometric alterations in the epileptic network regions remains largely unclear. In this study, a causal network of structural covariance (CaSCN) was proposed to map the causal effects of hippocampal atrophy on the network‐based morphometric alterations in mTLE. It was hypothesized that if cross‐sectional morphometric MRI data could be attributed temporal information, for example, by sequencing the data according to disease progression information, GCA would be a feasible approach for constructing a CaSCN. Based on a large cohort of mTLE patients (n = 108), the hippocampus‐associated CaSCN revealed that the hippocampus and the thalamus were prominent nodes exerting causal effects (i.e., GM reduction) on other regions and that the prefrontal cortex and cerebellum were prominent nodes being subject to causal effects. Intriguingly, compensatory increased gray matter volume in the contralateral temporal region and post cingulate cortex were also detected. The method unraveled richer information for mapping network atrophy in mTLE relative to the traditional methods of stage‐specific comparisons and structured covariance network. This study provided new evidence on the network spread mechanism in terms of the causal influence of hippocampal atrophy on progressive brain structural alterations in mTLE. Hum Brain Mapp 38:753–766, 2017. © 2016 Wiley Periodicals, Inc.
Quality upgrading in Ethiopian dairy value chains: dovetailing upstream and downstream perspectives

Abstract In this article, we analyze opportunities and constraints for upgrading product quality in the dairy value chain in Ethiopia. Our analysis is based on an integrated understanding of supply chain performance both from producer and from consumer perspectives. We outline as main drivers for quality upgrading: (a) factors that influence producers’ willingness to invest toward intensification by smallholder dairy farmers and cooperatives and (b) factors that induce consumer’s willingness to pay for healthy and nutritious dairy products delivered at specific retail outlets. Since there are large gaps between upstream producers incentives and downstream consumers motives, possibilities for dairy quality upgrading remain fairly limited. Given this market structure, decisive policy support is required for better tailoring producer’s investments with consumer preferences.
Detection of False Negative Pap Smears by Rapid Reviewing

OBJECTIVE To explore the diagnostic validity of rapid reviewing (RR) as a quality control method in cytologic laboratories. STUDY DESIGN Fourteen studies dealing with the detection of false negative Pap smears by RR were included in a metaanalysis. RESULTS The overall additional yield of positive slides, expressed as the percentage of all reviewed slides, is: 0.18% (95% confidence interval [CI]: .14-.21) for all cytologic abnormalities; 0.07% (CI: .05-.09) for squamous intraepithelial lesions (SIL) and 0.02% (CI: .01-.03) for high grade SIL. The false negative rate of primary screening, evaluated by RR, was 2.0% (CI: 1.5-2.6) for all cytologic abnormalities and 1.4% (CI: .8-2.1) for high grade SIL. The specificity of rapid rescreening was estimated as 97.2% (CI: 96.4-98.1). The positive predictive value of suspicion at RR is about 8.8%. Seven references contained historical data on full rescreening of a random sample of slides reported originally as negative. The results were also pooled and compared with RR. Complete rescreening is more sensitive, but if applied on only 10% of the negative workload, it would yield, on average, 4.7 times fewer extra positives, 5.6 times fewer SIL and 7.9 times fewer high grade SIL in comparison with RR of all sides. CONCLUSION RR of all smears initially reported as nonpositive is a more effective and a fortiori a more cost effective quality control method in comparison with full rescreening of a 10% random sample.
Modeling suicide in bipolar disorders

Suicide is a multicausal human behavior, with devastating and immensely distressing consequences. Its prevalence is estimated to be 20–30 times greater in patients with bipolar disorders than in the general population. The burden of suicide and its high prevalence in bipolar disorders make it imperative that our current understanding be improved to facilitate prediction of suicide and its prevention. In this review, we provide a new perspective on the process of suicide in bipolar disorder, in the form of a novel integrated model that is derived from extant knowledge and recent evidence.
Changes in lamellar microstructure by parallel twinning during creep in soft PST crystal of TiAl alloy

Compression creep tests of a Ti-48%Al (mole fraction) alloy were carried out at 1150K with soft-orientated PST crystal. Parallel twinning took placed uring the creep. Changes in lamellar microstructure caused by the parallel twinning were investigated, and their effects on creep deformation behavior were disc ussed. The results show that the parallel twinning occurs in an early stage of creep, and makes significant contribution to creep strain in the domains favorably oriented for the twinning. The nucleation of parallel twins finishes at a strain of about 3%. There is a critical resolved shear stress for parallel twinning, and it is about 50 Mpa in the Ti-48%Al PST crystals at 1150K. The activity of parallel twinning increases with increasing applied stress or in a coarse lamellar mater ial. The addition of parallel twins reduces the average value of lamellar spacin g. In general, the refinement of lamellar structure should improve creep resistance. However the strengthening by parallel twinning is not evident in creep of the soft PST crystals because the soft deformation modes are the dominant deformation mode in the crystals.
Targeted Temperature Management: Effects of Initial Protocol Implementation on Patient Outcomes

Background:Targeted temperature management (TTM) is a strategy used by critical care nurses to mitigate negative effects of out-of-hospital cardiac arrest (OHCA); however, integration and compliance of TTM protocols into routine clinical practice can be challenging. Objectives:The aims of this study are to (1) investigate the effects of initial TTM protocol implementation on patient mortality, length of stay, and discharge disposition among patients who experience OHCA and (2) evaluate initial compliance and potential barriers to newly implemented TTM protocol. Methods:A retrospective cohort design was used. Data were gathered on adult patients experiencing OHCA before and after immediate implementation of a TTM protocol within a large academic public hospital. Demographic and clinical data were abstracted from medical records of both TTM and non-TTM groups. Additional compliance data were gathered on the TTM group. Outcome variables included hospital mortality, length of stay, and discharge disposition. Results:Total accrual was 259. Mortality decreased after protocol implementation (89.4%, 75%, P < .05), which was supported in the regression analyses (P = .05; odds ratio, 2.8). A higher proportion of subjects were discharged home after the TTM protocol (21.5% discharged home after protocol implementation vs 5.1% discharged home before protocol implementation; P < .05). Full protocol compliance was 30%. Protocol documentation was inconsistent across units and personnel. Conclusions:Findings suggest that even initial implementation of TTM protocols can result in positive patient outcomes. Full compliance with protocols remains difficult. Critical care nurses are integral to initiation of and adherence to therapeutic hypothermia protocols and are in a key position to develop strategies for improved compliance across departments.
Comprehensive analysis of the clinical immuno-oncology landscape

Advances from immuno-oncology (IO) are changing the standard of care of many types of cancer, and the paradigm of cancer treatments and drug development is being rewritten on a regular basis. Moreover, an unprecedented number of new investigational agents and companies are entering the field of IO. As such, it has become challenging for oncology physicians conducting clinical trials, industry veterans developing IO drugs, and even regulators reviewing novel IO agents to keep track of the rapidly evolving landscape. To help the key stake holders in the field understand the latest IO landscape, we sought to present an unbiased, neutral, scientifically curated, and timely updated analysis of all the current IO agents in clinical development and the clinical trials testing these agents. We based our analyses on information collected from numerous trusted and publicly available sources. We have developed two databases. One database tracks 2004 IO agents (940 in clinical stage and 1064 in preclinical stage) against 303 targets, from 864 companies; the other tracks 3042 active clinical trials of these agents with a target enrollment of 577 076 patients. This report provides key analyses of these data. Furthermore, we will discuss a number of important and actionable trends in the current IO landscape: a large number of companies developing agents against the same IO targets; a rapid increase in the number of anti-PD-1/L1 combination studies, many of which are testing the same combinations and following inefficient patterns; and a significant increase in the number of small, investigator-initiated studies. For each of the findings, we speculate the causes and discuss a few initiatives that aim to address some of these challenges. Finally, by making these landscape analyses available, we aspire to inform the cancer community as they seek to strive for efficiencies and innovation while avoiding duplication.
In vivo imaging of the internal nasal valve during different conditions using optical coherence tomography

Previously, we proposed long‐range optical coherence tomography (LR‐OCT) to be an effective method for the quantitative evaluation of the nasal valve geometry. Here, the objective was to quantify the reduction in the internal nasal valve angle and cross‐sectional area that results in subjective nasal airway obstruction and to evaluate the dynamic behavior of the valve during respiration using LR‐OCT.
Fine needle aspiration

Objective: To identify cytological differences between mucosa-associated lymphoid tissue lymphoma (MALT-L) and nonneoplastic lymphocytes using thyroid liquid-based cytology (LBC). Study Design: We observed LBC and conventional specimens from 35 MALT-L cases, 3 diffuse large B-cell cell lymphoma (DLBCL) cases, and 44 prominent nonneoplastic lymphocytic infiltration cases. Results: In MALT-L cases, the incidence of lymphoglandular bodies in the LBC specimens was lower than that in the conventional specimens (p < 0.001). Moreover, the nuclear sizes in LBC specimens were larger than those in conventional specimens. In 62.9% of the MALT-L and all DLBCL specimens, large nuclei were present in > 10% of the lymphoid cells in LBC specimens. Two cases with prominent nonneoplastic lymphocytic infiltration also exhibited these findings. In LBC specimens, swollen naked nuclei with less punctate chromatin patterns and thin nuclear margins were observed in 92.1% of lymphoma and 20.5% of prominent nonneoplastic lymphocytic infiltration. Elongated nuclei were significantly more apparent in thyroid lymphoma than in prominent nonneoplastic lymphocytic infiltration (p < 0.001), with a significantly higher incidence in LBC specimens than in conventional specimens (p < 0.001). Conclusions: Lymphoglandular bodies are not reliable markers for lymphoma diagnosis using LBC specimens. Large, swollen naked, and elongated nuclei are useful in distinguishing thyroid lymphoma from nonneoplastic lymphocytes in LBC specimens. © 2018 The Author(s) Published by S. Karger AG, Basel
Recent Progress in Research on the Pathogenesis of Pulmonary Thromboembolism: An Old Story with New Perspectives

Pulmonary thromboembolism (PTE) is part of a larger clinicopathological entity, venous thromboembolism. It is also a complex, multifactorial disorder divided into four major disease processes including venous thrombosis, thrombus in transit, acute pulmonary embolism, and pulmonary circulation reconstruction. Even when treated, some patients develop chronic thromboembolic pulmonary hypertension. PTE is also a common fatal type of pulmonary vascular disease worldwide, but earlier studies primarily focused on the pathological changes in the blood component of the disease. With contemporary advances in molecular and cellular biology, people are becoming increasingly aware of coagulation pathways, the function of vascular smooth muscle cells, microparticles, and the inflammatory pathways that play key roles in PTE. Combined hypoxia and immune research has revealed that PTE should be regarded as a class of complex diseases caused by multiple factors involving the vascular microenvironment and vascular cell dysfunction.
Neck Pain Following Cervical Laminoplasty: Does Preservation of the C2 Muscle Attachments and/or C7 Matter?

Abstract Study Design Systematic review. Objective In patients aged 18 years or older, with cervical spondylotic myelopathy or ossification of the posterior longitudinal ligament (OPLL), does sparing the C2 muscle attachments and/or C7-preserving cervical laminoplasty lead to reduced postoperative axial pain compared with conventional C3 to C7 laminoplasty? Do these results vary based on early active postoperative cervical motion? Methods A systematic review of the English-language literature was undertaken for articles published between 1970 and August 17, 2012. Electronic databases and reference lists of key articles were searched to identify studies evaluating C2/C3- or C7-preserving cervical laminoplasty for the treatment of cervical spondylotic myelopathy (CSM) or OPLL in adults. Studies involving traumatic onset, cervical fracture, infection, deformity, or neoplasms were excluded, as were noncomparative studies. Two independent reviewers assessed the level of evidence quality using the grading of recommendations assessment, development and evaluation (GRADE) system, and disagreements were resolved by consensus. Results We identified 11 articles meeting our inclusion criteria. Only the randomized controlled trial (RCT) showed no significant difference in late axial pain (at 12 months) when C7 spinous muscle preservation was compared with no preservation. However, seven other retrospective cohort studies showed significant pain relief in the preserved group compared with the nonpreserved group. The preservation group included those with preservation of the C7 spinous process and/or attached muscles, the deep extensor muscles, or C2 muscle attachment and/or C3 laminectomy (as opposed to laminoplasty). One study that included preservation of either the C2 or C7 posterior paraspinal muscles found that only preservation of the muscles attached to C2 resulted in reduced postoperative pain. Another study that included preservation of either the C7 spinous process or the deep extensor muscles found that only preservation of C7 resulted in reduced postoperative pain. Conclusion Although there is conflicting data regarding the importance of preserving C7 and/or the semispinalis cervicis muscle attachments to C2, there is enough evidence to suggest that surgeons should make every attempt to preserve these structures whenever possible since there appears to be little downside to doing so, unless it compromises the neurologic decompression.
Modelling the impact of altered axonal morphometry on the response of regenerative nervous tissue to electrical stimulation through macro-sieve electrodes

Objective. Regenerated peripheral nervous tissue possesses different morphometric properties compared to undisrupted nerve. It is poorly understood how these morphometric differences alter the response of the regenerated nerve to electrical stimulation. In this work, we use computational modeling to explore the electrophysiological response of regenerated and undisrupted nerve axons to electrical stimulation delivered by macro-sieve electrodes (MSEs). Approach. A 3D finite element model of a peripheral nerve segment populated with mammalian myelinated axons and implanted with a macro-sieve electrode has been developed. Fiber diameters and morphometric characteristics representative of undisrupted or regenerated peripheral nervous tissue were assigned to core conductor models to simulate the two tissue types. Simulations were carried out to quantify differences in thresholds and chronaxie between undisrupted and regenerated fiber populations. The model was also used to determine the influence of axonal caliber on recruitment thresholds for the two tissue types. Model accuracy was assessed through comparisons with in vivo recruitment data from chronically implanted MSEs. Main results. Recruitment thresholds of individual regenerated fibers with diameters >2 µm were found to be lower compared to same caliber undisrupted fibers at electrode to fiber distances of less than about 90–140 µm but roughly equal or higher for larger distances. Caliber redistributions observed in regenerated nerve resulted in an overall increase in average recruitment thresholds and chronaxie during whole nerve stimulation. Modeling results also suggest that large diameter undisrupted fibers located close to a longitudinally restricted current source such as the MSE have higher average recruitment thresholds compared to small diameter fibers. In contrast, large diameter regenerated nerve fibers located in close proximity of MSE sites have, on average, lower recruitment thresholds compared to small fibers. Utilizing regenerated fiber morphometry and caliber distributions resulted in accurate predictions of in vivo recruitment data. Significance. Our work uses computational modeling to show how morphometric differences between regenerated and undisrupted tissue results in recruitment threshold discrepancies, quantifies these differences, and illustrates how large undisrupted nerve fibers close to longitudinally restricted current sources have higher recruitment thresholds compared to adjacently positioned smaller fibers while the opposite is true for large regenerated fibers.