Miracle-dz/UniFAR-FTUs huggingface dataset:
Common physiologic and proteomic biomarkers in pulmonary and coronary artery disease

Objective Chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) are leading causes of global morbidity and mortality. There is a well-known comorbidity between COPD and CAD, which is only partly explained by smoking and other known common risk factors. In order to better understand the relationship between COPD and CAD, we analyzed myocardial perfusion, pulmonary function and novel cardiovascular biomarkers in patients with symptoms suggesting myocardial ischemia. Methods A total of 396 subjects from the Swedish Biomarkers and Genetics CardioPulmonary Physiology Study (BiG CaPPS) were included, all of whom had been referred to myocardial perfusion imaging due to suspected myocardial ischemia. Subjects performed myocardial perfusion imaging (MPI), pulmonary function tests (PFT) and analysis of 92 proteomic biomarkers, previously associated with cardiovascular disease. Linear regression was used to study the relationship between MPI and PFT results and proteomic biomarkers. Results Subjects with CAD (n = 159) had lower diffusing capacity (DLCO) than patients without CAD (6.64 versus 7.17 mmol/(min*kPa*l); p = 0.004) in models adjusted for common covariates such as smoking, but also diabetes and brain natriuretic peptide (BNP). The association remained significant after additional adjustment for forced expiratory volume in one second (FEV1) (p = 0.009). Subjects with CAD, compared with subjects without CAD, had higher total airway resistance (0.37 vs 0.36 kPa/(l/s); p = 0.036). Among 92 protein biomarkers, nine were associated with a combined diagnosis of CAD and airflow obstruction: VSIG2, KIM1, FGF-23, REN, XCL1, GIF, ADM, TRAIL-R2 and PRSS8. Significance Diffusing capacity for carbon monoxide is decreased in patients with CAD, independently of decreased FEV1, diabetes, and elevated BNP. Several cardiovascular biomarkers are associated with co-existent CAD and airflow obstruction, but none with airflow obstruction only. The current findings indicate that the interaction between CAD and lung function is complex, including mechanisms beyond the known association between CAD and reduced ventilation.
Current concepts in fracture healing: temporal dynamization and applications for additive manufacturing

Abstract Objectives: Current surgical fracture treatment paradigms, which use rigid metallic constructs to heal bones, provide reasonable clinical outcomes; however, they do not leverage recent advances in our understanding of bone healing and mechanotransduction throughout bone healing. The objective of this review was to investigate the efficacy and potential clinical applicability of surgical techniques and implants that deliberately introduce interfragmentary motion throughout the healing process. Methods: The authors searched PubMed and Google Scholar databases for articles reporting on fracture repair using dynamic locking plates, dynamized surgical techniques, and reverse dynamization. Data collection also included assessment of additively manufactured (AM) implants that provide dynamic mechanical behaviors. Results: Forty articles were included for final review. It was found that accelerated rates of fracture healing can be achieved with staged 2-part surgeries or dynamic implant designs. Temporal dynamization, where static fixation of bones is followed by the introduction of micromotion and controlled loading, has been shown to improve callus volume and accelerate the healing response. Reverse dynamization, where micromotion is encouraged during early callus formation and arrested later, may represent a significant advance for the treatment of critical defect injuries. Advances in AM techniques will likely provide the ability to create high-resolution implants capable of dynamized and reverse dynamized modalities. Conclusions: There is no one-size-fits-all approach to optimization of fracture healing. However, it has been clearly demonstrated that fracture treatment can be enhanced by systematically altering the construct stiffness throughout the different phases of healing, which may be achieved with AM implant designs.
Nonfatal opioid overdoses before and after Covid-19: Regional variation in rates of change

Background The Covid-19 pandemic and its accompanying public-health orders (PHOs) have led to (potentially countervailing) changes in various risk factors for overdose. To assess whether the net effects of these factors varied geographically, we examined regional variation in the impact of the PHOs on counts of nonfatal overdoses, which have received less attention than fatal overdoses, despite their public health significance. Methods Data were collected from the Overdose Detection Mapping Application Program (ODMAP), which recorded suspected overdoses between July 1, 2018 and October 25, 2020. We used segmented regression models to assess the impact of PHOs on nonfatal-overdose trends in Washington DC and the five geographical regions of Maryland, using a historical control time series to adjust for normative changes in overdoses that occurred around mid-March (when the PHOs were issued). Results The mean level change in nonfatal opioid overdoses immediately after mid-March was not reliably different in the Covid-19 year versus the preceding control time series for any region. However, the rate of increase in nonfatal overdose was steeper after mid-March in the Covid-19 year versus the preceding year for Maryland as a whole (B = 2.36; 95% CI, 0.65 to 4.06; p = .007) and for certain subregions. No differences were observed for Washington DC. Conclusions The pandemic and its accompanying PHOs were associated with steeper increases in nonfatal opioid overdoses in most but not all of the regions we assessed, with a net effect that was deleterious for the Maryland region as a whole.
Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach

Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. The insight into the detailed biochemical composition of TNBC would help develop dedicated treatments. Thus, in this study Fourier Transform Infrared microspectroscopy combined with chemometrics and absorbance ratios investigation was employed to compare healthy controls with TNBC tissue before and after chemotherapy within the same patient. The primary spectral differences between control and cancer tissues were found in proteins, polysaccharides, and nucleic acids. Amide I/Amide II ratio decrease before and increase after chemotherapy, whereas DNA, RNA, and glycogen contents increase before and decrease after the treatment. The chemometric results revealed discriminatory features reflecting a clinical response scheme and proved the chemotherapy efficacy assessment with infrared spectroscopy is possible.
Determination of an optimum sampling unit of Ricania shantungensis (Hemiptera: Ricaniidae) eggs in persimmons

Even though the optimum sampling methods for invasive pests are very important in newly invaded areas, the standard sampling unit of Ricania shantungensis is still undeveloped in persimmons. Among all developmental stages of R. shantungensis, the egg has close relationship between its density and subsequent tree damage. Thus, this study was conducted to suggest an optimum sampling unit for R. shantungensis eggs in persimmons based on characteristics of its within-tree distribution pattern. The within-tree distribution pattern was characterized with 60 persimmon trees by cutting 12 branches at three vertical levels (low, middle, and high) in four horizontal criteria (east, west, south, and north) per tree. The sampling units were determined based on coefficient of variation (CV) and coefficient of determination (r2) calculated from egg mass numbers per 10 cm from the tip within a branch. In numbers of R. shantungensis egg masses, there was no significant difference (P > 0.05) horizontally, but significant (P < 0.05) difference vertically. More R. shantungensis eggs were found on terminal branches of each trunk. The 60 cm from the tip of branches in the terminal positions of each trunk was selected as the optimum sampling unit for R. shantungensis in persimmons because this unit has the lowest CV value and more than 0.9 of r2 value. Even though the optimum sample number per tree should be determined field-specifically, it would be acceptable to sample two or three branches by considering this pests’ recognizable damage level. This small sampling unit could make the sampling of R. shantungensis become more economical, precise, and consistent in persimmon fields.
Phase IB study of ziv-aflibercept plus pembrolizumab in patients with advanced solid tumors

Background The combination of antiangiogenic agents with immune checkpoint inhibitors could potentially overcome immune suppression driven by tumor angiogenesis. We report results from a phase IB study of ziv-aflibercept plus pembrolizumab in patients with advanced solid tumors. Methods This is a multicenter phase IB dose-escalation study of the combination of ziv-aflibercept (at 2–4 mg/kg) plus pembrolizumab (at 2 mg/kg) administered intravenously every 2 weeks with expansion cohorts in programmed cell death protein 1 (PD-1)/programmed death-ligand 1(PD-L1)-naïve melanoma, renal cell carcinoma (RCC), microsatellite stable colorectal cancer (CRC), and ovarian cancer. The primary objective was to determine maximum tolerated dose (MTD) and recommended dose of the combination. Secondary endpoints included overall response rate (ORR) and overall survival (OS). Exploratory objectives included correlation of clinical efficacy with tumor and peripheral immune population densities. Results Overall, 33 patients were enrolled during dose escalation (n=3) and dose expansion (n=30). No dose-limiting toxicities were reported in the initial dose level. Ziv-aflibercept 4 mg/kg plus pembrolizumab 2 mg/kg every 2 weeks was established as the MTD. Grade ≥3 adverse events occurred in 19/33 patients (58%), the most common being hypertension (36%) and proteinuria (18%). ORR in the dose-expansion cohort was 16.7% (5/30, 90% CI 7% to 32%). Complete responses occurred in melanoma (n=2); partial responses occurred in RCC (n=1), mesothelioma (n=1), and melanoma (n=1). Median OS was as follows: melanoma, not reached (NR); RCC, 15.7 months (90% CI 2.5 to 15.7); CRC, 3.3 months (90% CI 0.6 to 3.4); ovarian, 12.5 months (90% CI 3.8 to 13.6); other solid tumors, NR. Activated tumor-infiltrating CD8 T cells at baseline (CD8+PD1+), high CD40L expression, and increased peripheral memory CD8 T cells correlated with clinical response. Conclusion The combination of ziv-aflibercept and pembrolizumab demonstrated an acceptable safety profile with antitumor activity in solid tumors. The combination is currently being studied in sarcoma and anti-PD-1-resistant melanoma. Trial registration number NCT02298959.
Morphological aspects of the vasculogenesis and angiogenesis during prenatal edification of the circle of Willis: a review

In the literature, there are many articles reporting anatomical variations of circle of Willis (CoW), defined as those changes that lead to the inability of this anastomotic structure to maintain adequate brain flow. Because there is such a wide variation in the configuration of the CoW, its anatomical variations affect the hemodynamics of blood flow, thus contributing to the development of aneurysms or stroke. As such, we consider that a good knowledge of the embryological development of the constituent arteries of the CoW can shed some light on the causes of the appearance of its anatomical variants. Reviewing literature, we will present the embryological development of the constituting arteries of the CoW and will begin with vasculogenesis and angiogenesis of the vascular system as a whole. Then, we will focus on the embryological development of the internal carotid artery (ICA) and its branches because, starting with the embryological day 24, these arteries are the first vessels that begin to develop to provide the necessary blood for the primitive brain. As the hindbrain increases its volume, a larger amount of nutrients is needed. Because a larger amount of blood is required to be provided by the primitive ICAs, there is a need for arterial capacity development and thus the posterior circulation begin to take shape. At this stage, the posterior circulation consists of a plexiform arterial network that receives blood from the carotid artery through the carotid–vertebrobasilar anastomoses. At the 5–8 mm embryonic stage, these anastomoses begin to regress, and the basilar artery and vertebral arteries become independent of the ICA. We are pointing out on the process of regression of these primitive vessels, emphasizing the fact that their persistence represents the starting point for the appearance of anatomic anomalies of the CoW, which are identified in the adult individuals. In this review, we also present and illustrate some developmental abnormalities of the anterior and posterior parts of the CoW.
Shank promotes action potential repolarization by recruiting BK channels to calcium microdomains

Mutations altering the scaffolding protein Shank are linked to several psychiatric disorders, and to synaptic and behavioral defects in mice. Among its many binding partners, Shank directly binds CaV1 voltage activated calcium channels. Here, we show that the Caenorhabditis elegans SHN-1/Shank promotes CaV1 coupling to calcium activated potassium channels. Mutations inactivating SHN-1, and those preventing SHN-1 binding to EGL-19/CaV1 all increase action potential durations in body muscles. Action potential repolarization is mediated by two classes of potassium channels: SHK-1/KCNA and SLO-1 and SLO-2 BK channels. BK channels are calcium-dependent, and their activation requires tight coupling to EGL-19/CaV1 channels. SHN-1’s effects on AP duration are mediated by changes in BK channels. In shn-1 mutants, SLO-2 currents and channel clustering are significantly decreased in both body muscles and neurons. Finally, increased and decreased shn-1 gene copy number produce similar changes in AP width and SLO-2 current. Collectively, these results suggest that an important function of Shank is to promote microdomain coupling of BK with CaV1.
What predicts suicidality among psychologists? An examination of risk and resilience

Abstract Psychologists may have a uniquely high risk for suicide. We examined whether, among 172 psychologists, factors predicting suicide risk among the general population (e.g., gender and mental illness), occupational factors (e.g., burnout and secondary traumatic stress), and past trauma predicted suicidality. We also tested whether resilience and meaning in life were negatively related to suicidality and whether resilience buffered relationships between risk factors and suicidality. Family history of mental illness, number of traumas, and lifetime depression/anxiety predicted higher suicidality, whereas resilience predicted lower suicidality. At higher levels of resilience, the relationship between family history of suicide and suicidality was stronger.
Benzoxazolone‐arylpiperazinyl scaffold‐based PET ligand for 5‐HT7: Synthesis and biological evaluation

Efforts are underway to improve the diagnosis and treatment for neurological disorders like depression, anxiety, epilepsy, and schizophrenia. The G‐protein‐coupled receptors (GPCRs) 5‐HT7 receptor, the most recently identified member of 5‐HT receptor family dysregulation has an association with various central nervous system (CNS) disorders and its ligands have an edge as potential therapeutics. Here, we report the synthesis, characterization, and biological evaluation of diversely substituted methoxy derivatives of 2‐benzoxazolone arylpiperazine for targeting 5‐HT7 receptors. Out of all derivatives, only C‐2 substituted derivative, 3‐(4‐(4‐(2‐methoxyphenyl)piperazin‐1‐yl)butyl)benzoxazol‐2(3H)‐one/ABO demonstrate a high affinity for human 5‐HT7 receptors. [11C]ABO was obtained by O‐methylation of desmethyl‐precursor using [11C]CH3OTf in the presence of NaOH giving a high radiochemical yield of 25 ± 12% (decay‐corrected, n = 7) with stability up to 1.5 h postradiolabeling. In vitro autoradiography displays binding of [11C]ABO in accordance with 5‐HT7 distribution with a decrease of approximately 80% and 40% activity in the hippocampus and cerebellum brain region when administered with 10 µM cold ligand. Prefatory positron emission tomography scan results in Sprague‐Dawley (SD) rat brain revealed fast and high radioactivity build‐up in 5‐HT7 receptor‐rich regions, namely, the hippocampus (2.75 ± 0.16 SUV) and the cerebral cortex (2.27 ± 0.02 SUV) establishing selective targeting of [11C]ABO. In summary, these pieces of data designate [11C]ABO as a promising 5‐HT7 receptor ligand that can have possible roles in clinics after its further optimization on different animal models.
Predictors of compassion satisfaction and compassion fatigue in health care workers providing health and rehabilitation services in rural and remote locations: A scoping review

Abstract Introduction A better understanding of the predictors of compassion satisfaction and compassion fatigue in health care workers in rural and remote communities is needed to inform preventative interventions for this sector of the health workforce. Objective To identify predictors of compassion satisfaction and compassion fatigue in health care workers providing health and rehabilitation services in rural and remote locations. Design A scoping review informed by Arksey and O'Malley's five‐stage framework and the scoping review protocol of the PRISMA‐ScR statement. Findings The search yielded 946 articles, and 34 full texts were screened for eligibility, leaving 12 studies meeting the inclusion criteria. No studies on workers providing rehabilitation services were identified. Three studies assessed possible predictors of compassion satisfaction and compassion fatigue in health care workers, and all studies evaluated burnout. The most studied predictor variables were age, gender, profession and workload. Discussion This study identified potential risk and protective factors for health care workers that are likely relevant to those providing rehabilitation services in rural locations. Little is known about possible predictors of compassion satisfaction and compassion fatigue in professionals working in rural and remote areas outside of medicine and nursing or health care workers in rural community‐based settings. Conclusion Research examining predictors of compassion satisfaction and compassion fatigue in rehabilitation health care workers working in rural and remote locations is scant. Research that identifies risk and protective factors in this rapidly growing sector of the health care workforce is needed to inform the development of interventions that promote professional quality of life.
The coping insights evident through self‐reflection on stressful military training events: Qualitative evidence from self‐reflection journals

Abstract Research has demonstrated that adaptive forms of self‐reflection on stressor events and insight may strengthen resilient capacities. However, the coping insights that emerge during self‐reflection are notoriously under‐researched. In this research, we sought to explore the evidence for the self‐reflective activities and coping insights drawn from the Self‐Reflection and Coping Insight Framework and find evidence of new reflections or insights not captured within the framework. Qualitative analysis was used to examine weekly, written self‐reflective journals completed by Officer Cadets involved in a randomised‐controlled trial of Self‐Reflection Resilience Training. Sixty‐eight Officer Cadets who submitted their journals for analysis were included. Journals were analysed using a deductive thematic approach. Findings revealed that self‐reflective activities occurred frequently over the course of the intervention. Coping insights were comparatively less frequent, but conveyed complex ideas about the self in the context of stressor exposure, broad principles about stress and coping, and nuanced interpretations regarding the interaction between the efficacy of coping approaches and broader contextual and intrapersonal factors. These findings demonstrate the critical role of coping insight during Self‐Reflection Resilience Training, with implications for developing a validated self‐report measure of self‐reflective activity and coping insight.
Sex differences in clinical outcomes for obstructive hypertrophic cardiomyopathy in the USA: a retrospective observational study of administrative claims data

Objectives To evaluate sex differences in demographic and clinical characteristics, treatments and outcomes for patients with diagnosed obstructive hypertrophic cardiomyopathy (oHCM) in the USA. Setting Retrospective observational study of administrative claims data from MarketScan Commercial Claims and Encounters Database from IBM Watson Health. Participants Of the 28 million covered employees and family members in MarketScan, 9306 patients with oHCM were included in this analysis. Main outcome measures oHCM-related outcomes included heart failure, atrial fibrillation, ventricular tachycardia/ fibrillation, sudden cardiac death, septal myectomy, alcohol septal ablation (ASA) and heart transplant. Results Among 9306 patients with oHCM, the majority were male (60.5%, p<0.001) and women were of comparable age to men (50±15 vs 49±15 years, p<0.001). Women were less likely to be prescribed beta blockers (42.7% vs 45.2%, p=0.017) and undergo an implantable cardioverter-defibrillator (1.7% vs 2.6%, p=0.005). Septal reduction therapy was performed slightly more frequently in women (ASA: 0.08% vs 0.05%, p=0.600; SM: 0.35% vs 0.18%, p=0.096), although not statistically significant. Women were less likely to have atrial fibrillation (6.7% vs 9.9%, p<0.001). Conclusion Women were less likely to be prescribed beta blockers, ACE inhibitors, anticoagulants, undergo implantable cardioverter-defibrillator and have ventricular tachycardia/fibrillation. Men were more likely to have atrial fibrillation. Future research using large, clinical real-world data are warranted to understand the root cause of these potential treatment disparities in women with oHCM.
Set2 histone methyltransferase regulates transcription coupled-nucleotide excision repair in yeast

Helix-distorting DNA lesions, including ultraviolet (UV) light-induced damage, are repaired by the global genomic-nucleotide excision repair (GG-NER) and transcription coupled-nucleotide excision repair (TC-NER) pathways. Previous studies have shown that histone post-translational modifications (PTMs) such as histone acetylation and methylation can promote GG-NER in chromatin. Whether histone PTMs also regulate the repair of DNA lesions by the TC-NER pathway in transcribed DNA is unknown. Here, we report that histone H3 K36 methylation (H3K36me) by the Set2 histone methyltransferase in yeast regulates TC-NER. Mutations in Set2 or H3K36 result in UV sensitivity that is epistatic with Rad26, the primary TC-NER factor in yeast, and cause a defect in the repair of UV damage across the yeast genome. We further show that mutations in Set2 or H3K36 in a GG-NER deficient strain (i.e., rad16Δ) partially rescue its UV sensitivity. Our data indicate that deletion of SET2 rescues UV sensitivity in a GG-NER deficient strain by activating cryptic antisense transcription, so that the non-transcribed strand (NTS) of yeast genes is repaired by TC-NER. These findings indicate that Set2 methylation of H3K36 establishes transcriptional asymmetry in repair by promoting canonical TC-NER of the transcribed strand (TS) and suppressing cryptic TC-NER of the NTS.