Miracle-dz/UniFAR-FTUs huggingface dataset:
Primary palliative care competency framework for primary care and family physicians in India-Collaborative work by Indian Association of Palliative Care and Academy of Family Physicians of India

The discrepancy in the demand for palliative care and distribution of specialist palliative care services will force patients to be eventually cared for by primary care/family physicians in the community. This will necessitate primary care/family physicians to equip themselves with knowledge and skills of primary palliative care. Indian National Health Policy (2017) recommended the creation of continuing education programs as a method to empower primary care/family physicians. With this intention, a taskforce was convened for incorporating primary palliative care into family/primary care practice. The taskforce comprising of National and International faculties from Palliative Care and Family Medicine published a position paper in 2018 and subsequently brainstormed on the competency framework required for empowering primary care/family physicians. The competencies were covered under the following domains: knowledge, skills and attitude, ethical and legal aspects, communication and team work. The competency framework will be presented to the National Board of Examinations recommending to be incorporated in the DNB curriculum for Family Medicine.
Evaluation of Endometrial Receptivity by Measuring HOXA-10, HOXA-11, and Leukemia Inhibitory Factor Expression in Patients with Polycystic Ovary Syndrome

Context: Polycystic ovary syndrome (PCOS) is an important cause of infertility. In women with PCOS have increased rate of spontaneous abortion and reduced rate of conception. HOXA–10 and HOXA–11 are proteinous products of homeobox gene group and play an important role during implantation. Aims: The aim of this study was to evaluate endometrial receptivity by measuring HOXA–10, HOXA–11, and leukemia inhibitory factor (LIF) gene expressions in women with PCOS. Settings and Design: A tertiary referral center. Materials and Methods: This study was conducted on reproductive age women with abnormal uterine bleeding without sonographically proven anatomical reason. Endometrial sampling procedures were done in proliferative phase using low-pressure endometrial suction device to exclude endometrial pathology. HOXA–10, HOXA–11, and LIF gene expressions were measured from endometrial sampling material. Blood sample was taken to measure serum estradiol level on the day of endometrial sampling. Statistical Analysis Used: Statistical analysis was performed using SPSS software version 17 (SPSS Inc., Chicago, IL, USA). Mann–Whitney U-test was used to compare the variables. Results: A total of 53 patients were included in this study. Study group consisted of 33 patients with PCOS. Gene expressions of HOXA–10, HOXA–11, and LIF were significantly lower in patients with PCOS (P < 0.05). Conclusions: This study results showed that in patients with PCOS have decreased gene expression of HOXA-10, HOXA-11, and LIF which might contribute PCOS-related infertility.
The effect of gingival bleeding on oral home care practices in Saudi Arabia

Aim: The aim of this study was to determine the relationship between self-reported gingival bleeding, oral health perception, practices, and concerns. Materials and Methods: This cross-sectional survey among undergraduates of University of Prince Sattam Bin Abdulaziz, Al-Kharj, Saudi Arabia using a self-administered item structured questionnaire. Data analysis was done using Statistical Packages for the Social Sciences and P < 0.05 was considered significant. Results: The response rate was 96.3%. The prevalence of self-reported gingival bleeding among respondents was 48.79%. Individuals with gingival bleeding were significantly more likely to rate their dental and gingival health as fair/poor, use of strong brushing stroke during tooth brushing and worsening condition of teeth despite daily tooth brushing. They also expressed worry about the gingival color and less likely to be satisfied about the appearance of their teeth and to have received professional instruction on tooth brushing. Conclusion: Data from this survey revealed an established relationship between gingival bleeding, perceived dental and gingival health, worry about the color of gingiva, satisfaction with the appearance of the teeth, and visiting dental office because of gingival bleeding.
Predictive Value of Point-of-care Lactate Measurement in Patients Meeting Level II and III Trauma Team Activation Criteria that Present to the Emergency Department: A Prospective Study

Background: The aim of this study was to investigate the utility of early point-of-care (POC) lactate levels to help predict injury severity and ultimate emergency department (ED) disposition for trauma patients meeting Level II and III activation criteria. Methods: This was a blinded, prospective cohort study including a convenience sample of patients meeting our triage criteria for Level II or III team activation with stable vital signs. Bedside lactate samples were collected during the secondary survey. Clinical care/disposition was at the discretion of physicians who remained blinded to the bedside lactate result. An elevated lactate was defined as >2.0 mmol/L. Results: Ninety-six patients were in the study group; mean age was 41 ± 17 years, 26% were female, 57% were Hispanic, and 60% admitted. We found no difference in initial mean POC lactate levels (mmol/L) for admitted versus discharged groups and Injury Severity Score (ISS) ≥9 versus ISS <9 groups (3.71 [95% confidence interval (CI): 3.1–4.4] vs. 3.85 [95% CI: 2.8–4.9];P= 0.99 and 3.54 [95% CI: 2.7–4.4] vs. 3.89 [95% CI: 3.1–4.6];P= 0.60, respectively). Performance characteristics of early elevated lactate levels were poor both to predict need for hospital admission (sensitivity = 77% [65%–87%]; specificity = 26% [13%–43%]; negative predictive value [NPV] = 43% [27%–61%]; and positive predictive value [PPV] = 62% [56%–67%]) and to identify patients with ISS scores ≥9 (sensitivity = 76% [59%–89%]; specificity = 24% [14%–37%]; NPV = 65% [47%–80%]; and PPV = 36% [30%–41%]). Conclusions: For Level II/III, we found that early bedside lactate levels were not predictive of ISS ≥9 or the need for admission. Level of Evidence: III (diagnostic test).
The effect of visuospatial resolution on discharge variability among motor units and force–discharge relation

Although force steadiness varies with visuospatial information, accountable motor unit (MU) behaviors are not fully understood. This study investigated the modulation of MU discharges and force–discharge relation due to variations in the spatial resolution of visual feedback, with a particular focus on discharge variability among MUs. Fourteen young adults produced isometric force at 10% of maximal voluntary contraction (MVC) through index abduction, under the conditions of force trajectory displayed with low visual gain (LVG) and high visual gain (HVG). Together with smaller and more complex force fluctuations, HVG resulted in greater variabilities of the mean interspike interval and discharge irregularity among MUs than LVG did. Estimated via smoothening of a cumulative spike train of all MUs, global discharge rate was tuned to visual gain, with a more complex global discharge rate and a lower force–discharge relation in the HVG condition. These higher discharge variabilities were linked to larger variance of the common drive received by MUs for regulation of muscle force with higher visuospatial information. In summary, higher visuospatial information improves force steadiness with more complex force fluctuations, underlying joint effects of low-pass filter property of the musculotendon complex and central modulation of discharge variability among MUs.
Study of serum adiponectin and resistin in patients with obstructive sleep apnea

Background The syndrome of obstructive sleep apnea (OSA) is a very common disorder with several important complications and is still underdiagnosed. Obesity is considered to be a chronic disease rather than a lifestyle disorder. Adipose tissue secretory function is disturbed by chronic intermitted hypoxia occurring in OSA. The aim of this study was to study the level of serum adiponectin and resistin in patients with OSA and we tried to assess their association to different parameters of sleep disordered breathing (SDB) as well as concomitant comorbidities in each patient. Patients and methods This study contained two groups: Patients of group 1 included 30 newly diagnosed OSA patients and controls (group 2) included 15 healthy volunteers. All patients were subjected to overnight polysomnography, routine laboratory investigations, spirometry, and fasting serum adiponectin and resistin. Results Patients had statistically significant lower serum adiponectin level than controls while serum resistin levels were statistically significant higher in patients than controls. Moreover, serum adiponectin levels were significantly decreased with increased severity of OSA while serum resistin levels were increased significantly with increased severity of OSA. Moreover, there was a statistically significant decrease in serum adiponectin levels in the patients’ group with increasing number of comorbidities existing in every patient. There was a statistically significant increase in serum resistin levels in the patients’ group with increasing number of comorbidities existing in every patient. Conclusion This highlights the possible relationship of these hormones with the metabolic complications seen in OSA patients.
Nephroprotective effect of peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ agonists on thioacetamide-induced nephrotoxicity in rats

Aim This study, for the first time, evaluates the effect of PPARα/γ agonists on thioacetamide (TA)-induced nephrotoxicity in rats. Methods Male wistar rats were treated with TA (50 mg/kg, twice weekly for 6 weeks) to induce nephrotoxicity. Results Our results showed that bezafibrate and telmisartan caused significant decrease in urea, creatinine and renal malondialdehyde (MDA) which were elevated with TA administration. At the same time, both drugs caused significant increase in renal nitric oxide (NO) and renal superoxide dismutase (SOD) which were reduced with TA. Meanwhile, TA caused significant reduction in PPARα and PPARγ expression, telmisartan increased only PPARγ expression and bezafibrate increased only PPARα expression. Conclusion Our findings suggests that bezafibrate and telmisartan are protective against TA-induced nephrotoxicity possibly through their antioxidant activity.
Perception of dental professionals regarding integration of dental auxiliary into dental health delivery system

Background: The practical solution to handle increasing awareness toward dental treatment and cost of the dental treatment is integration of dental auxiliary into dental healthcare delivery system, and hence the objective of this study was to assess the perception of dental professionals regarding integration of dental auxiliaries into dental health delivery system in India. Materials and Methods: This cross-sectional study of Indian dentists was conducted using self-administered closed-ended questionnaire. Questions were asked to assess the opinions of the dentists on expanding the roles of dental auxiliaries and its consequences on dental services. The data were analyzed using Statistical Package for the Social Sciences version 22.0. The level of significance was kept at P < 0.05. Results: Of 230 dentists who participated in the study, 155 (67.39%) reported unfavorable opinion toward expanded duty dental auxiliaries. Among the studied consequences of expanding the functions of dental auxiliaries, cost-effectiveness of treatment had the highest mean score, followed by redundancy of dentists. Undergraduates reported that expanded function dental auxiliaries would lead to redundancy of dentists. Conclusion: It is recommended to train the auxiliaries to meet the expectations of patients, but this should be considered keeping in mind the existing situation of dental professionals in the country. Nonetheless, this study gives us information necessary to tailor health policies and improve the standards of the existing oral healthcare delivery in India.
Myrtenol Attenuates MRSA Biofilm and Virulence by Suppressing sarA Expression Dynamism

Methicillin-resistant Staphylococcus aureus (MRSA) is a deleterious human pathogen responsible for severe morbidity and mortality worldwide. The pathogen has attained high priority in the World Health Organization (WHO) – Multidrug-resistant (MDR) pathogens list. Emerging MDR strains of S. aureus are clinically challenging due to failure in conventional antibiotic therapy. Biofilm formation is one of the underlying mechanisms behind the antibiotic resistance. Hence, attenuating biofilm formation has become an alternative strategy to control persistent infections. The current study is probably the first that focuses on the antibiofilm and antivirulence potential of myrtenol against MRSA and its clinical isolates. Myrtenol exhibited a concentration-dependent biofilm inhibition without causing any harmful effect on cell growth and viability. Further, microscopic analysis validated the biofilm inhibitory efficacy of myrtenol against MRSA. In addition, myrtenol inhibited the synthesis of major virulence factors including slime, lipase, α-hemolysin, staphyloxanthin and autolysin. Inhibition of staphyloxanthin in turn sensitized the MRSA cells to healthy human blood and hydrogen peroxide (H2O2). Notably, myrtenol treated cells were deficient in extracellular DNA (eDNA) mediated autoaggregation as eDNA releasing autolysis was impaired by myrtenol. Biofilm disruptive activity on preformed biofilms was observed at concentrations higher than minimum biofilm inhibitory concentration (MBIC) of myrtenol. Also, the non-cytotoxic effect of myrtenol on human peripheral blood mononuclear cell (PBMC) was evidenced by trypan blue and Alamar blue assays. Transcriptional analysis unveiled the down-regulation of global regulator sarA and sarA mediated virulence genes upon myrtenol treatment, which is well correlated with results of phenotypic assays. Thus, the results of the present study revealed the sarA mediated antibiofilm and antivirulence potential of myrtenol against MRSA.
N-Glycosylation Site Analysis of Citrullinated Antigen-Specific B-Cell Receptors Indicates Alternative Selection Pathways During Autoreactive B-Cell Development

Many autoimmune diseases are hallmarked by autoreactive B and plasma cell responses that are directly or indirectly involved in disease pathogenesis. These B-cell responses show large variability between diseases, both in terms of the secreted autoantibody repertoire and the dynamics and characteristics of the underlying B-cell responses. Hence, different mechanisms have been proposed to explain the emergence of autoreactive B cells in an otherwise self-tolerant immune system. Notably, most mechanistic insights have been obtained from murine studies using models harboring genetic modifications of B and T cells. Given recent technological advances that have rendered autoreactive human B cells accessible for analysis, we here discuss the phenomenon of extensive N-glycosylation of the B-cell receptor (BCR) variable domain of a prototypic human autoreactive B-cell response and its potential role in the generation of autoimmunity. Anti-citrullinated protein antibodies (ACPA) hallmark the most disease-specific autoimmune response in Rheumatoid Arthritis (RA). Remarkably, ACPA-IgG are heavily N-glycosylated in the variable domain due to somatic mutations that generate abundant N-glycosylation consensus sequences. These sites, obtained from full-length BCR sequences of ACPA-expressing B cells from 12 ACPA-positive RA patients, were here analyzed in detail. Sites that required a single nucleotide mutation to be generated were defined as single somatic hypermutation (s-SHM) sites, whereas sites requiring multiple mutations were defined as m-SHM sites. IgG sequences of 12 healthy donors were used as control. Computational modeling of the germinal center reaction (CLONE algorithm) was used with the germline counterparts of ACPA-IgG heavy chain (HC) sequences to simulate the germinal center response. Our analyses revealed an abundance of N-glycosylation sites in ACPA-IgG HC that frequently required multiple mutations and predominated in specific positions. Based on these data, and taking into account recent insights into the dynamics of the ACPA-response during disease development, we here discuss the hypothesis that N-glycosylation sites in ACPA-IgG variable domains could lead to alternative, possibly antibody affinity-independent selection forces. Presumably, this occurs during germinal center responses allowing these B cells to escape from putative tolerance checkpoints, thereby driving autoreactive B cell development in the pathogenesis of RA.
Maintaining Integrity Under Stress: Envelope Stress Response Regulation of Pathogenesis in Gram-Negative Bacteria

The Gram-negative bacterial envelope is an essential interface between the intracellular and harsh extracellular environment. Envelope stress responses (ESRs) are crucial to the maintenance of this barrier and function to detect and respond to perturbations in the envelope, caused by environmental stresses. Pathogenic bacteria are exposed to an array of challenging and stressful conditions during their lifecycle and, in particular, during infection of a host. As such, maintenance of envelope homeostasis is essential to their ability to successfully cause infection. This review will discuss our current understanding of the σE- and Cpx-regulated ESRs, with a specific focus on their role in the virulence of a number of model pathogens.
Computed Tomography Radiomic Nomogram for Preoperative Prediction of Extrathyroidal Extension in Papillary Thyroid Carcinoma

Objectives: Determining the presence of extrathyroidal extension (ETE) is important for patients with papillary thyroid carcinoma (PTC) in selecting the proper surgical approaches. This study aimed to explore a radiomic model for preoperative prediction of ETE in patients with PTC. Methods: The study included 624 PTC patients (without ETE, n = 448; with minimal ETE, n = 52; with gross ETE, n = 124) whom were divided randomly into training (n = 437) and validation (n = 187) cohorts; all data were gathered between January 2016 and November 2017. Radiomic features were extracted from computed tomography (CT) images of PTCs. Key radiomic features were identified and incorporated into a radiomic signature. Combining the radiomic signature with clinical risk factors, a radiomic nomogram was constructed using multivariable logistic regression. Delong test was used to compare different receiver operating characteristic curves. Results: Five key radiomic features were incorporated into the radiomic signature, which were significantly associated with ETE (p < 0.001 for both cohorts) and slightly better than clinical model integrating significant clinical risk factors in the training cohort (area under the receiver operating characteristic curve (AUC), 0.791 vs. 0.778; F1 score, 0.729 vs. 0.714) and validation cohort (AUC, 0.772 vs. 0.756; F1 score, 0.710 vs. 0.692). The radiomic nomogram significantly improved predictive value in the training cohort (AUC, 0.837, p < 0.001; F1 score, 0.766) and validation cohort (AUC, 0.812, p = 0.024; F1 score, 0.732). Conclusions: The radiomic nomogram significantly improved the preoperative prediction of ETE in PTC patients. It indicated that radiomics could be a valuable method in PTC research.
Intrinsic Frequencies of the Resting-State fMRI Signal: The Frequency Dependence of Functional Connectivity and the Effect of Mode Mixing

The frequency characteristics of the resting-state BOLD fMRI (rs-fMRI) signal are of increasing scientific interest, as we discover more frequency-specific biological interpretations. In this work, we use variational mode decomposition (VMD) to precisely decompose the rs-fMRI time series into its intrinsic mode functions (IMFs) in a data-driven manner. The accuracy of the VMD decomposition of constituent IMFs is verified through simulations, with higher reconstruction accuracy and much-reduced mode mixing relative to previous methods. Furthermore, we examine the relative contribution of the VMD-derived modes (frequencies) to the rs-fMRI signal as well as functional connectivity measurements. Our primary findings are: (1) The rs-fMRI signal within the 0.01–0.25 Hz range can be consistently characterized by four intrinsic frequency clusters, centered at 0.028 Hz (IMF4), 0.080 Hz (IMF3), 0.15 Hz (IMF2) and 0.22 Hz (IMF1); (2) these frequency clusters were highly reproducible, and independent of rs-fMRI data sampling rate; (3) not all frequencies were associated with equivalent network topology, in contrast to previous findings. In fact, while IMF4 is most likely associated with physiological fluctuations due to respiration and pulse, IMF3 is most likely associated with metabolic processes, and IMF2 with vasomotor activity. Both IMF3 and IMF4 could produce the brain-network topology typically observed in fMRI, whereas IMF1 and IMF2 could not. These findings provide initial evidence of feasibility in decomposing the rs-fMRI signal into its intrinsic oscillatory frequencies in a reproducible manner.
Insights Into Enhanced Complement Activation by Structures of Properdin and Its Complex With the C-Terminal Domain of C3b

Properdin enhances complement-mediated opsonization of targeted cells and particles for immune clearance. Properdin occurs as dimers, trimers and tetramers in human plasma, which recognize C3b-deposited surfaces, promote formation, and prolong the lifetime of C3bBb-enzyme complexes that convert C3 into C3b, thereby enhancing the complement-amplification loop. Here, we report crystal structures of monomerized properdin, which was produced by co-expression of separate N- and C-terminal constructs that yielded monomer-sized properdin complexes that stabilized C3bBb. Consistent with previous low-resolution X-ray and EM data, the crystal structures revealed ring-shaped arrangements that are formed by interactions between thrombospondin type-I repeat (TSR) domains 4 and 6 of one protomer interacting with the N-terminal domain (which adopts a short transforming-growth factor B binding protein-like fold) and domain TSR1 of a second protomer, respectively. Next, a structure of monomerized properdin in complex with the C-terminal domain of C3b showed that properdin-domain TSR5 binds along the C-terminal α-helix of C3b, while two loops, one from domain TSR5 and one from TSR6, extend and fold around the C3b C-terminus like stirrups. This suggests a mechanistic model in which these TSR5 and TSR6 “stirrups” bridge interactions between C3b and factor B or its fragment Bb, and thereby enhance formation of C3bB pro-convertases and stabilize C3bBb convertases. In addition, properdin TSR6 would sterically block binding of the protease factor I to C3b, thus limiting C3b proteolytic degradation. The presence of a valine instead of a third tryptophan in the canonical Trp-ladder of TSR domains in TSR4 allows a remarkable ca. 60°-domain bending motion of TSR4. Together with variable positioning of TSR2 and, putatively, TSR3, this explains the conformational flexibility required for properdin to form dimers, trimers, and tetramers. In conclusion, the results indicate that binding avidity of oligomeric properdin is needed to distinguish surface-deposited C3b molecules from soluble C3b or C3 and suggest that properdin-mediated interactions bridging C3b-B and C3b-Bb enhance affinity, thus promoting convertase formation and stabilization. These mechanisms explain the enhancement of complement-mediated opsonization of targeted cells and particle for immune clearance.