Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinicogenomic Characteristics and Treatment of Young-Onset Colorectal Cancer Patients Treated With Palliative Therapy in Real-World Practice

Introduction Young-onset colorectal cancer (YOCR) is increasing. This study aimed to determine the difference between advanced YOCR and non-YOCR patient outcomes. Methods We retrospectively included patients with recurrent/metastatic colorectal cancer treated with palliative systemic therapy between 2016 and 2018. Diagnosis at < 50 years was defined as YOCR. Targeted sequencing was used to assess the mutational status. Results Among the 969 patients included, 210 (21.7%) were YOCR. The median progression-free survival with first-line chemotherapy (PFS1) was 9.7 vs 9.4 months (P = .755), and the median overall survival (OS) was 25.9 vs 22.3 months (P = .581) in the YOCR and the non-YOCR group, respectively. However, the youngest patients diagnosed at < 30 years showed poorer survival outcomes (median PFS1, 3.9 months; median OS, 8.6 months) compared with other age groups. PFS1 did not differ between YOCR and non-YOCR by choice of treatment regimen. Among the 340 patients with targeted sequencing results, YOCR had fewer APC mutations (61% vs 80%), but had similar KRAS (53% vs 48%), NRAS (7% vs 3%), and BRAF class I mutations (4% vs 6%). The median tumor mutational burden (TMB) was 10.9 vs 12.5 mut/Mb in YOCR and non-YOCR patients, respectively (P = .064). TMB increased with age in tumors with high microsatellite instability (Pearson’s R = .69, P = .028), but not in microsatellite-stable tumors (R = .02, P = .658). Conclusions Survival outcomes with palliative systemic therapy were similar between recurrent/metastatic YOCR and non-YOCR with an age cut-off of 50 years. However, patients diagnosed at < 30 years of age showed poorer outcomes compared with other age groups.
The Effect of Intranasal Oxytocin on the Association Between Couple Interaction and Sleep: A Placebo-Controlled Study

We investigated the association between couple interaction and sleep quality, as well as the modulation of this association by intranasal oxytocin. Data were gathered using an ecological momentary assessment design in 80 heterosexual couples. Results show that persons (especially men) who reported more satisfactory couple interaction also report better sleep quality. Furthermore, persons receiving oxytocin reported better sleep quality, and oxytocin promoted the association between couple interaction and fsleep quality (especially in women). ABSTRACT Objective Although most people in romantic relationships cosleep, biosocial modulators of sleep quality have only recently come into focus. Oxytocin (OT) might be one such modulator, as it had been shown to increase social attachment and safety. We investigated the association between everyday life couple interaction and sleep quality, as well as the effects of OT on this association. Methods Eighty heterosexual couples (N = 160 individuals, mean [standard deviation] age = 28 [5] years) were randomized to self-administer a) 32 international units of intranasal OT or b) placebo during 5 consecutive days. Each morning, they reported on sleep quality, and on subjective feelings of closeness and valence of couple interaction at a maximum of four times a day. Data were analyzed using hierarchical linear models. Results Subjective closeness (B = 0.43, t(73) = 3.80, p < . 001) and valence (negative − positive) of couple interaction (B = 0.50, t(73) = 3.91, p < . 001) were positively associated with sleep quality. Persons with OT reported higher levels of sleep quality than those without (B = 0.47, t(74) = 2.32, p = . 023). The association between closeness and sleep quality was stronger with OT than without (OT by closeness: B = 0.31, t(72) = 2.29, p = . 025; OT by valence of interaction: B = 0.27, t(72) = 1.77, p = . 081). Whereas the effect of couple interaction on sleep quality was strong in men, the OT effects were especially pronounced in women. Conclusions Our results suggest that enhancing closeness and positive couple interaction in cosleeping partners might be a way to improve sleep quality. The moderating effects of OT and sex on the association between couple interaction and sleep quality can have important implications for sleep therapy. Trial Registration: The study was preregistered at ClinicalTrials.gov (“Oxytocin, Couple Interaction, and Wound Healing” study, identifier NCT01594775). The present analyses were not preregistered.
MMBRG Protocol – Infants and Preschoolers: Myofunctional Orofacial Clinic Examination

ABSTRACT Purpose To present the Myofunctional Orofacial Clinical Examination Protocol belonging to the MMBGR Protocol - Infants and Preschoolers, including its validation. Methods Initially, test content-based validity was evaluated from the MBGR Protocol to be used with the age group between 6 and 71 months based on the bibliography and experience between the authors (original and current). For the content and appearance analysis, 10 speech therapists specialized in Orofacial Motricity attended and filled out an electronic form with dichotic and Likert scale questions in two moments. We used the Content Validity Index and the Exact Binomial Test. Then there was a validity based on the response processes analysis followed by a reliability of the Clinical Examination with 155 participants by 7 experienced and calibrated speech therapists, and the examiners between and within agreement was verified by the Intraclass Correlation Coefficient. Results There were additions, modifications, and exclusions of items according to the age group, resulting in the Myofunctional Orofacial Clinical Examination Protocol for Infants and Preschoolers, which obtained 90.5% agreement; and 100% of the appropriate scores by at least 90% of the specialists. In reliability, most items of the Extraoral and Intraoral Examination and Chewing obtained a reasonable to good, or even excellent, agreement. Conclusion The “Clinical Myofunctional Clinical Examination” was validated based on the test content, response process, and reliability and, along with the “Instructional” and the “Clinical History” is part of the “MMBGR Protocol - Infants and Preschoolers” for speech therapy activities in the age group between 6 and 71 months of age.
Diffusion Kernel Attention Network for Brain Disorder Classification

Constructing and analyzing functional brain networks (FBN) has become a promising approach to brain disorder classification. However, the conventional successive construct-and-analyze process would limit the performance due to the lack of interactions and adaptivity among the subtasks in the process. Recently, Transformer has demonstrated remarkable performance in various tasks, attributing to its effective attention mechanism in modeling complex feature relationships. In this paper, for the first time, we develop Transformer for integrated FBN modeling, analysis and brain disorder classification with rs-fMRI data by proposing a Diffusion Kernel Attention Network to address the specific challenges. Specifically, directly applying Transformer does not necessarily admit optimal performance in this task due to its extensive parameters in the attention module against the limited training samples usually available. Looking into this issue, we propose to use kernel attention to replace the original dot-product attention module in Transformer. This significantly reduces the number of parameters to train and thus alleviates the issue of small sample while introducing a non-linear attention mechanism to model complex functional connections. Another limit of Transformer for FBN applications is that it only considers pair-wise interactions between directly connected brain regions but ignores the important indirect connections. Therefore, we further explore diffusion process over the kernel attention to incorporate wider interactions among indirectly connected brain regions. Extensive experimental study is conducted on ADHD-200 data set for ADHD classification and on ADNI data set for Alzheimer’s disease classification, and the results demonstrate the superior performance of the proposed method over the competing methods.
IFL-GAN: Improved Federated Learning Generative Adversarial Network With Maximum Mean Discrepancy Model Aggregation

The generative adversarial network (GAN) is usually built from the centralized, independent identically distributed (i.i.d.) training data to generate realistic-like instances. In real-world applications, however, the data may be distributed over multiple clients and hard to be gathered due to bandwidth, departmental coordination, or storage concerns. Although existing works, such as federated learning GAN (FL-GAN), adopt different distributed strategies to train GAN models, there are still limitations when data are distributed in a non-i.i. d. manner. These studies suffer from convergence difficulty, producing generated data with low quality. Fortunately, we found that these challenges are often due to the use of a federated averaging strategy to aggregate local GAN models’ updates. In this article, we propose an alternative approach to tackling this problem, which learns a globally shared GAN model by aggregating locally trained generators’ updates with maximum mean discrepancy (MMD). In this way, we term our approach improved FL-GAN (IFL-GAN). The MMD score helps each local GAN hold different weights, making the global GAN in IFL-GAN getting converged more rapidly than federated averaging. Extensive experiments on MNIST, CIFAR10, and SVHN datasets demonstrate the significant improvement of our IFL-GAN in both achieving the highest inception score and producing high-quality instances.
Early life programming of health and disease: The long‐term consequences of obesity in pregnancy

Abstract The prevalence of overweight and obesity is rising in all parts of the world and, among young women, it presents a very clear danger during pregnancy. Women who are overweight or who gain excessive weight during pregnancy are at greater risk of complications in pregnancy and labour, and are more likely to lose their child to stillbirth or die themselves during pregnancy. This narrative review considers the evidence that, in addition to increasing risk of poor pregnancy outcomes, obesity has the capacity to programme foetuses to be at greater risk of cardiometabolic disorders later in life. An extensive body of evidence from prospective and retrospective cohorts, as well as record linkage studies, demonstrates associations of maternal obesity and/or gestational diabetes with cardiovascular disease, as well as type 1 and type 2 diabetes. Studies in animals suggest that these associations are underpinned by adaptations that occur in foetal life, which remodel the structures of major organs, including the brain, kidney and pancreas.
Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials

OBJECTIVE To assess the safety of empagliflozin in patients with type 2 diabetes and moderate to severe chronic kidney disease (CKD) (category G3–4) enrolled in clinical trials. RESEARCH DESIGN AND METHODS This analysis pooled data from 19 randomized, placebo-controlled, phase 1–4 clinical trials and 1 randomized, placebo-controlled extension study in which patients received empagliflozin 10 mg or 25 mg daily. Time to first occurrence of adverse events (AEs) was evaluated using Kaplan-Meier analysis and multivariable Cox regression models. RESULTS Among a total of 15,081 patients who received at least one study drug dose, 1,522, 722, and 123 were classified as having G3A, G3B, and G4 CKD, respectively, at baseline. Demographic and clinical characteristics were similar between treatment groups across CKD categories. Rates of serious AEs, AEs leading to discontinuation, and events of special interest (including lower limb amputations and acute renal failure [ARF]) were also similar between empagliflozin and placebo across CKD subgroups. In adjusted Cox regression analyses, risks for volume depletion and ARF were similar for empagliflozin and placebo in the combined group with CKD categories G3B and G4 and the G3A group. Notably lower risks were observed in both groups for hyperkalemia (hazard ratio 0.59 [95% CI 0.37–0.96, P = 0.0323] and 0.48 [0.26–0.91, P = 0.0243], respectively) and edema (0.47 [0.33–0.68, P < 0.0001] and 0.44 [0.28–0.68, P = 0.0002], respectively). CONCLUSIONS Use of empagliflozin in patients with type 2 diabetes and advanced CKD raised no new safety concerns and may have beneficial effects on the development of hyperkalemia and edema.
Efficacy of local prostaglandin analogues for vitiligo treatment: a systematic review and meta-analysis

ABSTRACT Background Vitiligo is a common cutaneous depigmentation disorder. Although multiple treatment options are available, no single modality is satisfactory for all patients. Several studies have demonstrated that prostaglandin analogues can potentially treat cutaneous depigmentation, but the evidence is limited to their inconsistent study design. Research design & methods A systematic review was performed for studies published before 29 June 2021, in PubMed, Embase, Web of Science, or the Cochrane Library. The primary outcome of pooled analysis was the repigmentation efficacy of local prostaglandin analogues compared with other therapies for vitiligo. Results Six randomized controlled trials (RCTs) and three non-RCTs were included in this systematic review, and seven studies among them were used for the meta-analysis. The pooled analysis demonstrated that local prostaglandin analogues could significantly increase repigmentation along with narrowband ultraviolet B phototherapy compared with phototherapy alone. Furthermore, the repigmentation efficacy of topical prostaglandin analogues was not significantly different from that of topical tacrolimus. In summary, local prostaglandin analogues either used alone or as add-on therapy could be safe and effective therapies for vitiligo.
Multiple molecular characteristics of circulating enterovirus types among paediatric hand, foot and mouth disease patients after EV71 vaccination campaign in Wuxi, China

Abstract The molecular properties of the circulating causative agents of hand, foot and mouth disease (HFMD) in Wuxi remain unclear, posing diagnostic and prevention challenges. Additionally, in several regions of mainland China, the EV71 immunisation drastically reduced related cases and altered the HFMD pathogen spectrum, while the precise situation in Wuxi remained unknown. To address these issues, paediatric HFMD cases diagnosed in the clinic were enrolled and anal swabs were acquired in the spring of 2019. The 5′-UTR and VP1 genes were interpreted using RT-nPCR with degenerate primers to confirm their genotypes. Following that, the entire genome sequences of each viral type were recovered, allowing for the interpretation of several molecular properties. A total of 249 clinically confirmed HFMD cases had their anal swabs taken for viral identification, from which the genome sequences of seven genotypes were recovered. Coxsackievirus A16 is the most prevalent type, followed by Coxsackievirus A6, A10, A2, A4, A5 and Echovirus 11, all of which were genetically determined for the first time in Wuxi. Phylogenetic and recombination analyses were used to evaluate their evolutionary relationships with other strains found in other regions. Noticeably, a CVA16 subtype, responsible for a large proportion of the observed cases, phylogenetically clustered within clade B1a along with some strains from other countries, was the first one to be reported in China. Furthermore, some recombination events were inferred from strains detected in sporadic cases, particularly the recombination between CVA2 and CVA5 strains. Our investigation elucidated the multiple molecular characteristics of the HFMD causal enterovirus strains in Wuxi, underlining the potential hazards associated with these circulating viral types in the population and aiding in future surveillance and prevention of this disease.
Simplified classification of cavernous internal carotid artery tortuosity: a predictor of procedural complexity and clinical outcomes in mechanical thrombectomy

ABSTRACT Objectives Thromboaspiration catheters are increasingly used for the endovascular treatment of large vessel stroke (LVS), while tortuous vascular anatomy still remains one major challenge in mechanical thrombectomy. Prompt assessing and understanding cavernous internal carotid artery (cICA) tortuosity may help to predict procedural complexities of mechanical thrombectomy and thus improve the clinical outcomes. Methods A retrospective review was performed on a cohort of LVS patients with thromboaspiration catheter. Simplified classification of cICA tortuosity was applied by measurement of the angle of the posterior genus (P) and the height from the peak of the posterior genu to the trough of the anterior genu (D). Statistical analyses were performed to analyze differences among the obtained types of cICA tortuosity regarding procedural characteristics and clinical outcomes. Results A total of 150 patients with LVS proximal to the internal ICA terminus and middle cerebral artery (MCA) were included in this study, and three types of cICA tortuosity were defined by the simplified classification. The index, such as patients ages and hypertension, procedural fluoroscopy time, the degree of cICA tortuosity, first-pass success, final reperfusion, and 90-day mortality showed significant differences among the three types (P < 0.05), while 90-day good outcome (mRS 0–2) only presented significant difference between Type I and Type III (P < 0.05). Conclusions The study indicated that the grading of cICA tortuosity is highly correlated with procedural complexity and clinical outcome in mechanical thrombectomy. The proposed classification system may be helpful in pre-procedure prognostication complexity and clinical outcomes. Abbreviations:LVS: large vessel stroke; cICA: cavernous internal carotid artery; mRS: modified Rankin Scale; AIS: acute ischemic stroke; MCA: middle cerebral artery; M1: first division of middle cerebral artery; M2: second division of middle cerebral artery; M3: third division of middle cerebral artery; TICI: Thrombolysis In Cerebral Infarction; TICI 2b: two-thirds of occluded territory reperfusion; DSA: digital subtraction angiography; FT: fluoroscopy time.
Country-specific lockdown measures in response to the COVID-19 pandemic and its impact on tuberculosis control: a global study

ABSTRACT The objective of this study was to describe country-specific lockdown measures and tuberculosis indicators collected during the first year of the COVID-19 pandemic. Data on lockdown/social restrictions (compulsory face masks and hand hygiene; international and local travel restrictions; restrictions to family visits, and school closures) were collected from 24 countries spanning five continents. The majority of the countries implemented multiple lockdowns with partial or full reopening. There was an overall decrease in active tuberculosis, drug-resistant tuberculosis, and latent tuberculosis cases. Although national lockdowns were effective in containing COVID-19 cases, several indicators of tuberculosis were affected during the pandemic.
Greater ectopic fat deposition and liver fibroinflammation and lower skeletal muscle mass in people with type 2 diabetes

Type 2 diabetes (T2D) is associated with significant end‐organ damage and ectopic fat accumulation. Multiparametric magnetic resonance imaging (MRI) can provide a rapid, noninvasive assessment of multiorgan and body composition. The primary objective of this study was to investigate differences in visceral adiposity, ectopic fat accumulation, body composition, and relevant biomarkers between people with and without T2D.
COVID‐19 vaccination status and testing rates in Finland—A potential cause for bias in observational vaccine effectiveness analysis

COVID‐19 vaccination effectiveness has been monitored in observational studies (test‐negativity design or traditional cohort design), but these studies have not addressed the potential behavioral bias between vaccinated and unvaccinated individuals. We aimed to address this by comparing COVID‐19 testing rates between vaccination status and whether vaccination changes the testing rates. We found that three times vaccinated had least tests performed during the pandemic and unvaccinated had the highest testing rate. Each vaccination dose increased the testing rate. In conclusion the observational studies addressing vaccine effectiveness should also present testing rates between vaccinated and unvaccinated to address the potential behavioral bias.
T‐cell responses to SARS‐CoV‐2 Omicron spike epitopes with mutations after the third booster dose of an inactivated vaccine

The rapidly spreading severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron variant contains more than 30 mutations that mediate escape from antibody responses elicited by prior infection or current vaccines. Fortunately, T‐cell responses are highly conserved in most individuals, but the impacts of mutations are not clear. Here, we showed that the T‐cell responses of individuals who underwent booster vaccination with CoronaVac were largely protective against the SARS‐CoV‐2 Omicron spike protein. To specifically estimate the impact of Omicron mutations on vaccinated participants, 16 peptides derived from the spike protein of the ancestral virus or Omicron strain with mutations were used to stimulate peripheral blood mononuclear cells (PBMCs) from the volunteers. Compared with the administration of two doses of vaccine, booster vaccination substantially enhanced T‐cell activation in response to both the ancestral and Omicron epitopes, although the enhancement was slightly weakened by the Omicron mutations. Then, the peptides derived from these spike proteins were used separately to stimulate PBMCs. Interestingly, compared with the ancestral peptides, only the peptides with the G339D or N440K mutation were detected to significantly destabilize the T‐cell response. Although more participants need to be evaluated to confirm this conclusion, our study nonetheless estimates the impacts of mutations on T‐cell responses to the SARS‐CoV‐2 Omicron variant.
SCAMPP: Scaling Alignment-Based Phylogenetic Placement to Large Trees

Phylogenetic placement, the problem of placing a “query” sequence into a precomputed phylogenetic “backbone” tree, is useful for constructing large trees, performing taxon identification of newly obtained sequences, and other applications. The most accurate current methods, such as pplacer and EPA-ng, are based on maximum likelihood and require that the query sequence be provided within a multiple sequence alignment that includes the leaf sequences in the backbone tree. This approach enables high accuracy but also makes these likelihood-based methods computationally intensive on large backbone trees, and can even lead to them failing when the backbone trees are very large (e.g., having 50,000 or more leaves). We present SCAMPP (SCaling AlignMent-based Phylogenetic Placement), a technique to extend the scalability of these likelihood-based placement methods to ultra-large backbone trees. We show that pplacer-SCAMPP and EPA-ng-SCAMPP both scale well to ultra-large backbone trees (even up to 200,000 leaves), with accuracy that improves on APPLES and APPLES-2, two recently developed fast phylogenetic placement methods that scale to ultra-large datasets. EPA-ng-SCAMPP and pplacer-SCAMPP are available at https://github.com/chry04/PLUSplacer.