Miracle-dz/UniFAR-FTUs huggingface dataset:
Questions and facts regarding denosumab discontinuation among postmenopausal women

In contrast to other chronic diseases where treatment is lifelong, in osteoporosis treatment discontinuation may be considered under certain conditions. Bisphosphonates (BPs) remain the mainstay of osteoporosis treatment for the last three decades and both their long biological half-life in bone and their retained anti-fracture effect, even after their discontinuation, have inevitably influenced our perception regarding the therapeutic approach of this disease [1]. The only easily accessible and valuable surrogate marker to guide our decisions regarding discontinuing treatment or not is bone mineral density (BMD), due to its strong correlation with fracture prediction [2]. However, although BMD can be efficiently used as a target while on treatment [1], it can be revisited not sooner than 1 year from discontinuation, which is probably a relatively long time for a chronic condition to remain unmonitored. For example, no one would consider repeating HbA1c or lipid measurements 1 year after discontinuation of diabetes or hyperlipidemia treatment, respectively, while probably the majority of physicians would not have advised cessation of treatment even if the patient was perfectly controlled under therapy. However, given the lack of reliable predictive information from bone markers following osteoporosis treatment discontinuation [3], BMD measurement is the only tool to monitor the course of the disease post-treatment.
Effect of maternal smoking during pregnancy on Tourette syndrome and chronic tic disorders among offspring: a systematic review and meta-analysis

Current studies have controversial reports about the effect of maternal smoking during pregnancy (MSDP) on the risk of psychiatric disorders among offspring. The purpose of this systematic review and meta-analysis was to assess the effect of MSDP on the risk of Tourette syndrome (TS) and chronic tic disorders (CTD) among offspring. A systematic search using PubMed, Scopus, and Web of Science was conducted up to July 2019 to retrieve potential studies in English. Fixed and random-effects meta-analyses was performed to estimate pooled relative risk (RR) with 95% confidence interval (CI) according to heterogeneity. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale. Heterogeneity among studies was explored using the I2 statistic. Of the 641 studies from the initial search, 7 were included in the quantitative synthesis (3 cohort and 4 case control studies). Overall, MSDP increased the risk of TS and CTD among the offspring by 35% (pooled RR, 1.35; 95% CI, 1.17–1.56; I2=45.8%; P-value=0.08). The results of this meta-analysis revealed that there is a significant association between MSDP and the risk of TS and CTD in offspring, and MSDP may be considered a potential risk factor for TS and CTD.
A Comparison of Psychological Readiness and Patient-Reported Function Between Sexes After Anterior Cruciate Ligament Reconstruction.

CONTEXT Postoperative functional and return-to-sport outcomes after anterior cruciate ligament reconstruction (ACLR) differ by sex. However, whether sex disparities are observed in patient-reported outcome measures (PROMS) before return to sport after ACLR is unclear. OBJECTIVES To compare common PROMS between young men and women who had not yet returned to sport after ACLR. DESIGN Cross-sectional study. SETTING University laboratory. MAIN OUTCOME MEASURE(S) Forty-five young men (age = 18.7 ± 2.7 years, time since surgery = 6.8 ± 1.4 months) and 45 matched for age (±1 year) and time since surgery (±1 month; age = 18.8 ± 2.8 years, time since surgery = 6.9 ± 1.4 months) with ACLR participated. Participants completed the Tegner Activity Scale, ACL Return to Sport After Injury scale, Tampa Scale of Kinesiophobia, International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Score, and Knee Injury and Osteoarthritis Outcome Score (KOOS). The PROMS were compared between men and women using Mann-Whitney U tests. Odds ratios were calculated to evaluate the odds of a male reporting a PROM value above the previously established normative value as compared with a female. RESULTS Sex differences were present for the IKDC score (P = .01) and KOOS Pain score (P = .04) but not for the Tegner activity level (P = .22), ACL Return to Sport after Injury scale score (P = .78), Tampa Scale of Kinesiophobia score (P = .64), or other KOOS subscales (P values = .40 to .52). The odds of reporting values above normative levels differed only for the IKDC score (odds ratio = 2.72, 95% confidence level = 1.16, 6.38). CONCLUSIONS After ACLR, young men and women reported similar levels of knee-related function, fear of movement, and readiness for return to sport and were equally likely to meet clinically meaningful normative values before return to sport. Overreliance on patient reports or objective functional outcomes in evaluating patient progress and readiness for return to sport after ACLR may limit clinicians in their ability to comprehensively evaluate and develop individualized interventional approaches that optimize patient outcomes.
Comparison of in-hospital mortality risk prediction models from COVID-19

Objective Our objective is to compare the predictive accuracy of four recently established outcome models of patients hospitalized with coronavirus disease 2019 (COVID-19) published between January 1st and May 1st 2020. Methods We used data obtained from the Veterans Affairs Corporate Data Warehouse (CDW) between January 1st, 2020, and May 1st 2020 as an external validation cohort. The outcome measure was hospital mortality. Areas under the ROC (AUC) curves were used to evaluate discrimination of the four predictive models. The Hosmer–Lemeshow (HL) goodness-of-fit test and calibration curves assessed applicability of the models to individual cases. Results During the study period, 1634 unique patients were identified. The mean age of the study cohort was 68.8±13.4 years. Hypertension, hyperlipidemia, and heart disease were the most common comorbidities. The crude hospital mortality was 29% (95% confidence interval [CI] 0.27–0.31). Evaluation of the predictive models showed an AUC range from 0.63 (95% CI 0.60–0.66) to 0.72 (95% CI 0.69–0.74) indicating fair to poor discrimination across all models. There were no significant differences among the AUC values of the four prognostic systems. All models calibrated poorly by either overestimated or underestimated hospital mortality. Conclusions All the four prognostic models examined in this study portend high-risk bias. The performance of these scores needs to be interpreted with caution in hospitalized patients with COVID-19.
Effect of Focusing on Maryam’s Flower During the First Stage of the Labor on the Labor Pain, Labor Duration, and Levels of Comfort and Satisfaction

This randomized controlled experimental study was conducted with an intervention group (n = 61) and a control group (n = 63) consisting of primipara pregnant women. The pregnant women in the intervention group were asked to focus their attention on Maryam’s flower opening its leaf buds and imagine the labor’s progress during the course of their labor. The VAS was administered to each group at specific times (at 4–5 cm, 6–7 cm, 8–9 cm cervical dilatation) to determine their level of labor pain. A statistically significant difference was found between the groups’ mean pain scores at 4–5 cm, 6–7 cm, and 8–9 cm cervical dilatation (p < .05). The labor duration of the pregnant women in the intervention group was significantly shorter than that of the pregnant women in the control group (p = .017). The physical comfort level of the intervention group was significantly higher than that of the control group at 8–9 cm cervical dilatation (p = .039).
Multiplexed Processing of Vibrotactile Information in the Mouse Primary Somatosensory Cortex

The primary somatosensory (S1) cortex plays a key role in distinguishing different sensory stimuli. Vibrotactile touch information is conveyed from the periphery to the S1 cortex through three major classes of mechanoreceptors: slowly adapting type 1 (SA1), rapidly adapting (RA), and Pacinian (PC) afferents. It has been a long-standing question whether specific populations in the S1 cortex preserve the peripheral segregation by the afferent submodalities. Here, we investigated whether S1 neurons exhibit specific responses to two distinct vibrotactile stimuli, which excite different types of mechanoreceptors (e.g., SA1 and PC afferents). Using in vivo two-photon microscopy and genetically encoded calcium indicator, GCaMP6s, we recorded calcium activities of S1 L2/3 neurons. At the same time, static (<1 Hz) and dynamic (150 Hz) vibrotactile stimuli, which are known to excite SA1 and PC, respectively, were pseudorandomly applied to the right hind paw in lightly anesthetized mice. We found that most active S1 neurons responded to both static and dynamic stimuli, but more than half of them showed preferred responses to either type of stimulus. Only a small fraction of the active neurons exhibited specific responses to either static or dynamic stimuli. However, the S1 population activity patterns by the two stimuli were markedly distinguished. These results indicate that the vibrotactile inputs driven by excitation of distinct submodalities are converged on the single cells of the S1 cortex, but are well discriminated by population activity patterns composed of neurons that have a weighted preference for each type of stimulus.
Tooth attachment and pleurodont implantation in lizards: Histology, development, and evolution

Squamates present a unique challenge to the homology and evolution of tooth attachment tissues. Their stereotypically pleurodont teeth are fused in place by a single “bone of attachment”, with seemingly dubious homology to the three‐part tooth attachment system of mammals and crocodilians. Despite extensive debate over the interpretations of squamate pleurodonty, its phylogenetic significance, and the growing evidence from fossil amniotes for the homology of tooth attachment tissues, few studies have defined pleurodonty on histological grounds. Using a sample of extant squamate teeth that we organize into three broad categories of implantation, we investigate the histological and developmental properties of their dental tissues in multiple planes of section. We use these data to demonstrate the specific soft‐ and hard‐tissue features of squamate teeth that produce their disparate tooth implantation modes. In addition, we describe cementum, periodontal ligaments, and alveolar bone in pleurodont squamates, dental tissues that were historically thought to be restricted to extant mammals and crocodilians. Moreover, we show how the differences between pleurodonty and thecodonty do not relate to the identity of the tooth attachment tissues, but rather the arrangements of homologous tissues around the teeth.
Association between periodontal disease and inflammatory bowel disease: a systematic review and meta-analysis

Abstract Objective The aim of this systematic review was to investigate the association between periodontal disease (PD) and inflammatory bowel disease (IBD), and its two major forms Crohn’s disease (CD) and ulcerative colitis (UC). Materials and methods We searched articles in PubMed/MEDLINE, Web of Science, and LILACS published until March 2020. Observational studies evaluating the coexistence of PD in IBD and reported values of clinical periodontal parameters, or radiographic bone loss; and IBD diagnosis established by clinical, radiological, endoscopic and histological criteria were deemed eligible. Results A total of 9 studies were included (33,216 individuals). Only one study reported longitudinal data on IBDs onset in patients with PD. Several case-control studies reported coexistence. Meta-analysis showed that the presence of PD was associated with IBD (2.78 [95%CI 1.36–5.69]). PD was strongly associated both with CD (3.41 [95%CI 1.36–8.56]) and UC (3.98 [95%CI 2.02–7.87]). Conclusion This review presents clear evidence for an association between PD and IBDs. Future studies should avoid non-longitudinal designs and focus on addressing direction. PD screening may be included in the multidisciplinary management of IBD patients. The mere theoretical possibility that PD may predispose to IBDs may be of key significance due to the rising incidence of diseases.
Epidemiology of Functional Seizures Among Adults Treated at a University Hospital

Key Points Question What is the period prevalence and comorbidity of patients with functional seizures? Findings This case-control study including 3341 patients with functional seizures (period prevalence, 0.14%) identified from all patients at a university medical center found that posttraumatic stress disorder and sexual assault trauma were associated with functional seizures. Novel associations were identified, including cerebrovascular disease. Meaning The findings of this study suggest that patients who present with seizures and additional psychiatric comorbidities, sexual assault trauma history, or cerebrovascular disease should be referred for video electroencephalogram diagnostic assessment.
Dose–response association between fluid overload and in-hospital mortality in critically ill patients: a multicentre, prospective, observational cohort study

Objectives Fluid management is important in ensuring haemodynamic stability in critically ill patients, but can easily lead to fluid overload (FO). However, the optimal fluid balance plot or range for critically ill patients is unknown. This study aimed to explore the dose–response relationship between FO and in-hospital mortality in critically ill patients. Design Multicentre, prospective, observational study. Setting Eighteen intensive care units (ICUs) of 16 tertiary hospitals in China. Participants Critically ill patients in the ICU for more than 3 days. Primary outcome measures and analyses FO was defined as the ratio of the cumulative fluid balance (L) and initial body weight (kg) on ICU admission, expressed as a percentage. Maximum FO was defined as the peak value of FO during the first 3 days of ICU admission. Logistic regression models with restricted cubic splines were used to explore the pattern and magnitude of the association between maximum FO and risk of in-hospital mortality. Age, sex, Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score on admission, main diagnosis on admission to ICU, comorbidities, time of maximum FO, mechanical ventilation, renal replacement therapy, use of vasopressors and centres were adjusted in multivariable analysis. Results A total of 3850 patients were included in the study, 929 (24.1%) of whom died in the hospital. For each 1% L/kg increase in maximum FO, the risk of in-hospital mortality increased by 4% (adjusted HR (aHR) 1.04, 95% CI 1.03 to 1.05, p<0.001). A maximum FO greater than 10% was associated with a 44% increased HR of in-hospital mortality compared with an FO less than 5% (aHR 1.44, 95% CI 1.27 to 1.67). Notably, we found a non-linear dose–response association between maximum FO and in-hospital mortality. Conclusions Both higher and negative fluid balance levels were associated with an increased risk of in-hospital mortality in critically ill patients. Trial registration number ChiCTR-ECH-13003934.
Creation of a Continent Urinary Bladder Reservoir Vascularized by Omentum as a Possible Surgical Option for Canine Trigonal/Urethral Urothelial Carcinoma

Abstract Surgical procedures that maintain continence with minimal complication following resection of trigono-urethral urothelial carcinoma (UC) are limited in canines; therefore, palliative options are often pursued. A feasible tumor resection option may improve disease control and survival. The study’s objective was to evaluate a continent urine reservoir created from the urinary bladder body and vascularized solely by omentum. We hypothesized that a viable urine reservoir could be created, and staged omentalization would provide improved vascularity. Nine normal female Beagles were randomized to one of three groups. Group A urinary bladders were transected cranial to the ureteral papillae to create a closed bladder vesicle which was concomitantly omentalized. Group B underwent omentalization two weeks prior to vesicle creation. Based on Group A and B results, Group C underwent neoureterocystostomy and omentalization followed by neoreservoir formation and tube cystostomy 2 weeks later. Serial ultrasounds and histopathology confirmed adequate omental neovascularization in Groups B and C with continent Group C neoreservoirs maintained for 2 months. Some pylectasia and ureteral dilation was documented in all Group C dogs at variable timepoints. Progressive hydroureteronephrosis developed in 2/6 kidneys. Transient azotemia was noted in only 1 Group C dog, although all developed treatable urinary tract infections. The sample size is limited, and the efficacy of this technique in providing disease control for UC is unknown. However, this novel option could allow for primary UC resection while providing continence and limiting complications. Postoperative local or systemic adjuvant therapy, ultrasonographic neoreservoir monitoring, and BRAF analysis would be indicated.
Communicating risk in human-wildlife interactions: How stories and images move minds

Effectively communicating risk is critical to reducing conflict in human-wildlife interactions. Using a survey experiment fielded in the midst of contentious public debate over flying fox management in urban and suburban areas of Australia, we find that stories with characters (i.e., narratives) are more effective than descriptive information at mobilizing support for different forms of bat management, including legal protection, relocation, and habitat restoration. We use conditional process analysis to show that narratives, particularly with accompanying images, are effective because they cause emotional reactions that influence risk perception, which in turn drives public opinion about strategies for risk mitigation. We find that prior attitudes towards bats matter in how narrative messages are received, in particular in how strongly they generate shifts in affective response, risk perception, and public opinion. Our results suggest that those with warm prior attitudes towards bats report greater support for bat dispersal when they perceive impacts from bats to be more likely, while those with cool priors report greater support for bat protection when they perceive impacts from bats to be more positive, revealing 1) potential opportunities for targeted messaging to boost public buy-in of proposals to manage risks associated with human-wildlife interactions, and 2) potential vulnerabilities to disinformation regarding risk.
Efficacy of Early Prophylaxis Against Catheter-Associated Thrombosis in Critically Ill Children: A Bayesian Phase 2b Randomized Clinical Trial.

OBJECTIVES We obtained preliminary evidence on the efficacy of early prophylaxis on the risk of central venous catheter-associated deep venous thrombosis and its effect on thrombin generation in critically ill children. DESIGN Bayesian phase 2b randomized clinical trial. SETTING Seven PICUs. PATIENTS Children less than 18 years old with a newly inserted central venous catheter and at low risk of bleeding. INTERVENTION Enoxaparin adjusted to anti-Xa level of 0.2-0.5 international units/mL started at less than 24 hours after insertion of central venous catheter (enoxaparin arm) versus usual care without placebo (usual care arm). MEASUREMENTS AND MAIN RESULTS At the interim analysis, the proportion of central venous catheter-associated deep venous thrombosis on ultrasonography in the usual care arm, which was 54.2% of 24 children, was significantly higher than that previously reported. This resulted in misspecification of the preapproved Bayesian analysis, reversal of direction of treatment effect, and early termination of the randomized clinical trial. Nevertheless, with 30.4% of 23 children with central venous catheter-associated deep venous thrombosis on ultrasonography in the enoxaparin arm, risk ratio of central venous catheter-associated deep venous thrombosis was 0.55 (95% credible interval, 0.24-1.11). Including children without ultrasonography, clinically relevant central venous catheter-associated deep venous thrombosis developed in one of 27 children (3.7%) in the enoxaparin arm and seven of 24 (29.2%) in the usual care arm (p = 0.02). Clinically relevant bleeding developed in one child randomized to the enoxaparin arm. Response profile of endogenous thrombin potential, a measure of thrombin generation, was not statistically different between trial arms. CONCLUSIONS These findings suggest the efficacy and safety of early prophylaxis that should be validated in a pivotal randomized clinical trial.
At-Risk Testing for Pompe Disease Using Dried Blood Spots: Lessons Learned for Newborn Screening

Pompe disease (GSD II) is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme acid-α-glucosidase (GAA, EC 3.2.1.20), leading to generalized accumulation of lysosomal glycogen especially in the heart, skeletal, and smooth muscle, and the nervous system. It is generally classified based on the age of onset as infantile (IOPD) presenting during the first year of life, and late onset (LOPD) when it presents afterwards. In our study, a cohort of 13,627 samples were tested between January 2017 and December 2018 for acid-α-glucosidase (GAA, EC 3.2.1.20) deficiency either by fluorometry or tandem mass spectrometry (MS). Testing was performed for patients who displayed conditions of unknown etiology, e.g., CK elevations or cardiomyopathy, in the case of infantile patients. On average 8% of samples showed activity below the reference range and were further assessed by another enzyme activity measurement or molecular genetic analysis. Pre-analytical conditions, like proper drying, greatly affect enzyme activity, and should be assessed with measurement of reference enzyme(s). In conclusion, at-risk testing can provide a good first step for the future introduction of newborn screening for Pompe disease. It yields immediate benefits for the patients regarding the availability and timeliness of the diagnosis. In addition, the laboratory can introduce the required methodology and gain insights in the evaluation of results in a lower throughput environment. Finally, awareness of such a rare condition is increased tremendously among local physicians which can aid in the introduction newborn screening.