Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of exosomal miRNA in chemotherapy resistance of Colorectal cancer: A systematic review

The third most common malignancy has been identified as Colorectal cancer (CRC) that conducive to death in most cases. Chemoresistance is a common obstacle to CRC treatment. Circulating exosomal microRNAs (miRNAs) have been shown to reverse chemo‐resistance and are promising biomarkers for CRC. The capacity of engineered exosomes to cross biological barriers and deliver functional miRNAs could be used to achieve these proposes. The object of this review is the investigation of the role of exosomal miRNA in the chemo‐resistance, diagnosis, and prognosis of CRC. Using Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, electronic databases, PubMed, EMBASE, Web of Science, Scopus were searched from January 1990 to November 2020. Ultimately, eight articles included five in vitro (16 cell lines) and three in vivo examinations. Three studies demonstrated that increasing or decreasing mRNA expression was associated with increasing and decreasing cell proliferation in vitro. The presence of miRNA in two studies increased the sensitivity of the drug and exhibited a considerable growth inhibitory effect on cancer cell proliferation. The apoptotic rate was significantly increased in four studies by increased mRNA expression and reduced mrna expression. Tumor volume of xenograft models in three studies suppressed by antitumor miRNA activity. In contrast, anti‐miRNA activity in one study decreased the tumor volume. Exosomal miRNAs can be regulators of chemo‐resistance and predict adverse outcomes in CRC patients. In sum, exosomes containing miRNAs can be a promising biomarker for the prognosis and diagnosis of CRC. Subsequent research should be a focus on delineating the function of exosomal miRNA before clinical use.
Female Representation and Academic Leadership in Facial Plastic and Reconstructive Surgery

Despite increasing the numbers of women entering the field, underrepresentation of women in otolaryngology has been reported. In the subspecialty of facial plastic and reconstructive surgery (FPRS), female representation and academic leadership have not been formally characterized. Our study aims to identify female representation and academic leadership roles in FPRS.
Reporting suspicion of child maltreatment - a 5 yr follow-up of public dental health care workers in Norway

Abstract Objective This study examined stability and change of Norwegian dental health care workers’ mandated reporting of suspected child maltreatment from 2014 to 2019 as well as the influence on reporting practices from regional, sociodemographic- and attitudinal factors. It was hypothesised that those factors associate independently with reporting practices across the survey period. Methods In 2014 a census of 1542 dental health care workers employed in the public dental health care service (PDHS) were invited to participate in an electronic survey and 1200 (response 77.8%) consented to participation. Corresponding figures in 2019 were 1791 and 1270 (response 70.9%). Of the 1200 participants in 2014, 591 participated in 2019 (follow up 49.3%). Results A total of 58% and 25.7% of the dental health care workers confirmed ever reporting and avoidance of reporting in both survey years whereas 24.6% and 17.2% changed the status of ever- and avoiding reporting across time. The likelihood of being a stable reporter was greatest in experienced participants, those living in eastern parts of Norway and confirming professional obligations to report. At the population level, 59.6% and 79.5% confirmed ever reporting of suspected maltreatment in 2014 and 2019. Corresponding figures for confirmed avoidance of reporting were 33.9% and 37.9%. Conclusion Reporting of suspected child maltreatment is maintained at a relatively high level and varies by socio-demographic and attitudinal concerns.
A machine learning–based biological aging prediction and its associations with healthy lifestyles: the Dongfeng–Tongji cohort

This study aims to establish a biological age (BA) predictor and to investigate the roles of lifestyles on biological aging. The 14,848 participants with the available information of multisystem measurements from the Dongfeng–Tongji cohort were used to estimate BA. We developed a composite BA predictor showing a high correlation with chronological age (CA) (r = 0.82) by using an extreme gradient boosting (XGBoost) algorithm. The average frequency hearing threshold, forced expiratory volume in 1 second (FEV1), gender, systolic blood pressure, and homocysteine ranked as the top five important features for the BA predictor. Two aging indexes, recorded as the AgingAccel (the residual from regressing predicted age on CA) and aging rate (the ratio of predicted age to CA), showed positive associations with the risks of all‐cause (HR (95% CI) = 1.12 (1.10–1.14) and 1.08 (1.07–1.10), respectively) and cause‐specific (HRs ranged from 1.06 to ∼1.15) mortality. Each 1‐point increase in healthy lifestyle score (including normal body mass index, never smoking, moderate alcohol drinking, physically active, and sleep 7–9 h/night) was associated with a 0.21‐year decrease in the AgingAccel (95% CI: −0.27 to −0.15) and a 0.4% decrease in the aging rate (95% CI: −0.5% to −0.3%). This study developed a machine learning–based BA predictor in a prospective Chinese cohort. Adherence to healthy lifestyles showed associations with delayed biological aging, which highlights potential preventive interventions.
Microstructure Aware Modeling Of Biochemical Transport In Arterial Blood Clots

Flow-mediated transport of biochemical species is central to thrombotic phenomena. Comprehensive three-dimensional modeling of flow-mediated transport around realistic macroscale thrombi poses challenges owing to their arbitrary heterogeneous microstructure. Here, we develop a microstructure aware model for species transport within and around a macroscale thrombus by devising a custom preconditioned fictitious domain formulation for thrombus-hemodynamics interactions, and coupling it with a fictitious domain advection-diffusion formulation for transport. Microstructural heterogeneities are accounted through a hybrid discrete particle-continuum approach for the thrombus interior. We present systematic numerical investigations on unsteady arterial flow within and around a three-dimensional macroscale thrombus; demonstrate the formation of coherent flow structures around the thrombus which organize advective transport; illustrate the role of the permeation processes at the thrombus boundary and subsequent intra-thrombus transport; and characterize species transport from bulk flow to the thrombus boundary and vice versa.
Stereotactic radiosurgery for secretory pituitary adenomas: systematic review and International Stereotactic Radiosurgery Society practice recommendations.

OBJECTIVE A systematic review was performed to provide objective evidence on the use of stereotactic radiosurgery (SRS) in the management of secretory pituitary adenomas and develop consensus recommendations. METHODS The authors performed a systematic review of the English-language literature up until June 2018 using the PRISMA guidelines. The PubMed (Medline), Embase, and Cochrane databases were searched. A total of 45 articles reporting single-institution outcomes of SRS for acromegaly, Cushing's disease, and prolactinomas were selected and included in the analysis. RESULTS For acromegaly, random effects meta-analysis estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rates were 97.0% (95% CI 96.0%-98.0%), 44.0% (95% CI 35.0%-53.0%), and 17.0% (95% CI 13.0%-23.0%), respectively. For Cushing's disease, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 92.0% (95% CI 87.0%-95.0%), 48.0% (95% CI 35.0%-61.0%), and 21.0% (95% CI 13.0%-31.0%), respectively. For prolactinomas, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 93.0% (95% CI 90.0%-95.0%), 28.0% (95% CI 19.0%-39.0%), and 12.0% (95% CI 6.0%-24.0%), respectively. Meta-regression analysis did not show a statistically significant association between mean margin dose with crude endocrine remission rate or mean margin dose with development of any new hypopituitarism rate for any of the secretory subtypes. CONCLUSIONS SRS offers effective tumor control of hormone-producing pituitary adenomas in the majority of patients but a lower rate of endocrine improvement or remission.
Designing and pilot testing a novel high-definition transcranial burst electrostimulation device for neurorehabilitation

Objective. Non-invasive brain stimulation has been promoted to facilitate neuromodulation in treating neurological diseases. Recently, high-definition (HD) transcranial electrical stimulation and a novel electrical waveform combining a direct current (DC) and theta burst stimulation (TBS)-like protocol were proposed and demonstrated high potential to enhance neuroplastic effects in a more-efficient manner. In this study, we designed a novel HD transcranial burst electrostimulation device and to preliminarily examined its therapeutic potential in neurorehabilitation. Approach. A prototype of the transcranial burst electrostimulation device was developed, which can flexibly output a waveform that combined a DC and TBS-like protocol and can equally distribute the current into 4 × 1 HD electrical stimulation by automatic impedance adjustments. The safety and accuracy of the device were then validated in a series of in vitro experiments. Finally, a pilot clinical trial was conducted to assess its clinical safety and therapeutic potential on upper-extremity rehabilitation in six patients with chronic stroke, where patients received either active or sham HD transcranial burst electrostimulation combined with occupational therapy three times per week for four weeks. Main results. The prototype was tested, and it was found to comply with all safety requirements. The output parameters were accurate and met the clinical study needs. The pilot clinical study demonstrated that the active HD transcranial burst electrostimulation group had greater improvement in voluntary motor function and coordination of the upper extremity than the sham control group. Additionally, no severe adverse events were noted, but slight skin redness under the stimulus electrode immediately after stimulation was seen. Conclusions. The results demonstrated the feasibility of incorporating the HD electrical DC and TBS-like protocol in our device; and the novel neuromodulatory device produced positive neurorehabilitation outcomes in a safe fashion, which could be the basis for the future clinical implementation for treating neurological diseases. Trial registration: ClinicalTrials.gov Identifier: NCT04278105. Registered on 20 February 2020.
Medical, welfare, and educational challenges and psychological distress in parents caring for an individual with 22q11.2 deletion syndrome: A cross‐sectional survey in Japan

Parents of children with 22q11.2 deletion syndrome (22q11DS) experience distress not only due to multimorbidity in the patients, but also due to professionals' lack of understanding about 22q11DS and insufficient support systems. This study investigated relationships between medical, welfare, and educational challenges and parental psychological distress. A cross‐sectional survey was conducted on primary caregivers of children with 22q11DS. Participants included 125 parents (114 mothers, 91.2%; average age = 44.3 years) who reported their challenges, psychological distress, and child's comorbidities of 22q11DS. Results showed that the difficulty in going to multiple medical institutions (β = 0.181, p < 0.05) and lack of understanding by welfare staff and insufficient welfare support systems for 22q11DS (β = 0.220–0.316, all p < 0.05) were associated with parental psychological distress, even after adjusting for child's comorbidities. In the subsample of parents whose child attended an educational institution, inadequate management in classroom and mismatch between service and users in educational settings were associated with psychological distress (β = 0.222–0.296, all p < 0.05). This study reveals the importance of assessing not only severity of comorbidities in 22q11DS, but also the medical, welfare, and educational challenges for parental mental health.
Can Propofol Be Used to Assess the Presence of the Rectoanal Inhibitory Reflex During Anorectal Manometry Studies?

ABSTRACT Objectives: To study changes in intra-anal pressure (IAP) and characteristics of the rectoanal inhibitory reflex (RAIR) during anorectal manometry (ARM) in patients undergoing anesthesia induction with propofol. Methods: Prospective study in which ARM was performed at baseline while patients were awake and repeated after propofol-induced anesthesia. We studied IAP and the presence and characteristics of the RAIR before and after propofol. Results: A total of 27 patients were included (63% male; 9.2 years). Three patients had obstructive symptoms after Hirschsprung disease repair (HSCR), and 24 had intractable constipation. At baseline, the RAIR was present on 21 of 27 patients and absent on 6 of 27. Of the six patients with an absent RAIR, it remained absent in four of six (three known HSCR, and one new diagnosis of IAS achalasia), and two of six had a normal RAIR during propofol. Therefore, RAIR was present in all patients with constipation. The mean resting IAP was significantly lower after propofol. The percentage of IAS relaxation after lower balloon volume inflations was significantly higher during propofol (P < 0.05). No difference was observed over the latency time or the total relaxation time after propofol. Conclusions: Propofol can be used to assess the presence of the RAIR during ARM in children who are uncooperative and undergoing other procedures under anesthesia. On the other hand, propofol significantly reduces the resting IAP and increases the percentage of internal anal sphincter relaxation after balloon distention. These findings may impact the interpretation to decide if an intervention is needed, or if there is a possible spinal neuropathy.
Impact of the COVID‐19 pandemic on population‐based cancer registry

The COVID‐19 pandemic has caused disruptions to national health systems and impacted health outcomes worldwide. However, the extent to which surveillance systems, such as population‐based cancer registration, have been affected was not reported. Here we sought to evaluate the effect of the pandemic on registry operations across different areas and development levels worldwide. We investigated the impact of COVID‐19 on three main areas of cancer registry operations: staffing, financing and data collection. An online survey was administered to 750 member registries of the International Association for Cancer Registries. Among 212 responding registries from 90 countries, 65.6% reported a disruption in operations, ranging between 45% in south‐eastern Asia and 87% in the Latin America and Caribbean. Active data collection was disrupted more than case notifications or hybrid methods. In countries categorized with low Human Development Index (HDI), a greater number of registries reported a negative impact (81.3%) than in very high HDI countries (57.8%). This contrast was highest in term of impact on financing: 9/16 (56%) registries in low HDI countries reported a current or an expected decline in funding, compared to 7/108 (7%) in very high HDI countries. With many cancer registries worldwide reporting disruption to their operations during the early COVID‐19 pandemic, urgent actions are needed to ensure their continuity. Governmental commitment to support future registry operations as an asset to disease control, alongside a move toward electronic reporting systems will help to ensure the sustainability of cancer surveillance worldwide.
Telomere dynamics in relation to experimentally increased locomotion costs and fitness in great tits

Evidence that telomere length (TL) and dynamics can be interpreted as proxy for ‘life stress’ experienced by individuals stems largely from correlational studies. We tested for effects of an experimental increase of workload on telomere dynamics by equipping male great tits (Parus major) with a 0.9 g backpack for a full year. In addition, we analysed associations between natural life‐history variation, TL and TL dynamics. Carrying 5% extra weight for a year did not significantly accelerate telomere attrition. This agrees with our earlier finding that this experiment did not affect survival or future reproduction. Apparently, great tit males were able to compensate behaviourally or physiologically for the increase in locomotion costs we imposed. We found no cross‐sectional association between reproductive success and TL, but individuals with higher reproductive success (number of recruits) lost fewer telomere base pairs in the subsequent year. We used the TRF method to measure TL, which method yields a TL distribution for each sample, and the association between reproductive success and telomere loss was more pronounced in the higher percentiles of the telomere distribution, in agreement with the higher impact of ageing on longer telomeres within individuals. Individuals with longer telomeres and less telomere shortening were more likely to survive to the next breeding season, but these patterns did not reach statistical significance. Whether successful individuals are characterized by losing fewer or more base pairs from their telomeres varies between species, and we discuss aspects of ecology and social organisation that may explain this variation.
Early Diagnosis, Early Stratification, and Early Intervention to Deliver Precision Medicine in IBD

Abstract Despite huge advances in understanding the molecular basis of IBD, clinical management has continued to rely on a “trial and error” approach. In addition, a therapeutic ceiling has emerged whereby even the most effective interventions are only beneficial for approximately 30% of patients. Consequently, several tools have been developed to aid stratification and guide treatment-decisions. We review the potential application for many of these precision medicine approaches, which are now almost within reach. We highlight the importance of early action (and avoiding inaction) to ensure the best outcomes for patients and how combining early action with precision tools will likely ensure the right treatment is delivered at the right time and place for each individual person living with IBD. The lack of clinical impact to date from precision medicine, despite much hype and investment, should be tempered with the knowledge that clinical translation can take a long time, and many promising breakthroughs might be ready for clinical implementation in the near future. We discuss some of the remaining challenges and barriers to overcome for clinical adoption. We also highlight that early recognition, early diagnosis, early stratification, and early intervention go hand in hand with precision medicine tools. It is the combination of these approaches that offer the greatest opportunity to finally deliver on the promise of precision medicine in IBD.
Computer Methods and Programs in Biomedicine

Background and Objectives: Craniometric landmarks are essential in many biomedical applications, such as morphometric analysis or forensic identiﬁcation. The process of locating landmarks is usually a manual and slow task, highly inﬂuenced by fatigue, skills and the experience of the practitioner. Localization errors are propagated and magniﬁed in subsequent steps, which can result in incorrect measurements or assumptions. Thereby, standardization, reliability and reproducibility lay the foundations for the necessary accuracy in subsequent measurements or anatomical analysis. In this paper, we present an automatic method to annotate 3D surface skull models taking into account anatomical and geometrical features. Methods: The proposed method follows a hybrid structure where a deformable template is used to initialize the landmark positions. Then, a reﬁnement stage is applied using prior anatomical knowledge to ensure a correct placement. Our proposal is validated over thirty 3D skull scans of male Caucasians, acquired by hand-held surface scanning, and a set of 58 craniometric landmarks. A statistical analysis was carried out to analyze the inter-and intra-observer variability of manual annotations and the automatic results, along with a visual assessment of the ﬁnal results. Results: Inter-observer errors show signiﬁcant differences, which are reﬂected in the expert consensus used as reference. The average localization error was 2 . 19 ± 1 . 5 mm when comparing the automatic landmarks to the reference location. The subsequent visual analysis conﬁrmed the reliability of the reﬁnement method for most landmarks. Conclusions: Repeated manual annotations show a high variability depending on both skills and expertise of the observer, and landmarks’ location and characteristics. In contrast, the automatic method provides an accurate, robust and reproducible alternative to the tedious and error-prone task of manual landmarking.
Efficient computation of Faith's phylogenetic diversity with applications in characterizing microbiomes

The number of publicly available microbiome samples is continually growing. As data set size increases, bottlenecks arise in standard analytical pipelines. Faith's phylogenetic diversity (Faith's PD) is a highly utilized phylogenetic alpha diversity metric that has thus far failed to effectively scale to trees with millions of vertices. Stacked Faith's phylogenetic diversity (SFPhD) enables calculation of this widely adopted diversity metric at a much larger scale by implementing a computationally efficient algorithm. The algorithm reduces the amount of computational resources required, resulting in more accessible software with a reduced carbon footprint, as compared to previous approaches. The new algorithm produces identical results to the previous method. We further demonstrate that the phylogenetic aspect of Faith's PD provides increased power in detecting diversity differences between younger and older populations in the FINRISK study's metagenomic data.