Miracle-dz/UniFAR-FTUs huggingface dataset:
Baby Genomics: Tracing the Evolutionary Changes That Gave Rise to Placentation

Abstract It has long been challenging to uncover the molecular mechanisms behind striking morphological innovations such as mammalian pregnancy. We studied the power of a robust comparative orthology pipeline based on gene synteny to address such problems. We inferred orthology relations between human genes and genes from each of 43 other vertebrate genomes, resulting in ∼18,000 orthologous pairs for each genome comparison. By identifying genes that first appear coincident with origin of the placental mammals, we hypothesized that we would define a subset of the genome enriched for genes that played a role in placental evolution. We thus pinpointed orthologs that appeared before and after the divergence of eutherian mammals from marsupials. Reinforcing previous work, we found instead that much of the genetic toolkit of mammalian pregnancy evolved through the repurposing of preexisting genes to new roles. These genes acquired regulatory controls for their novel roles from a group of regulatory genes, many of which did in fact originate at the appearance of the eutherians. Thus, orthologs appearing at the origin of the eutherians are enriched in functions such as transcriptional regulation by Krüppel-associated box-zinc-finger proteins, innate immune responses, keratinization, and the melanoma-associated antigen protein class. Because the cellular mechanisms of invasive placentae are similar to those of metastatic cancers, we then used our orthology inferences to explore the association between placenta invasion and cancer metastasis. Again echoing previous work, we find that genes that are phylogenetically older are more likely to be implicated in cancer development.
Comparison of 5 Different PET Radiopharmaceuticals for the Detection of Recurrent Medullary Thyroid Carcinoma

Purpose The aim of this study is to investigate and compare the performance of different PET radiopharmaceuticals for the detection of recurrent medullary thyroid carcinoma (MTC) by performing a network meta-analysis (NMA) using direct comparison studies with 2 or more PET radiopharmaceuticals. Methods PubMed and EMBASE were searched for the studies evaluating the performance of PET or PET/CT for the detection of recurrent MTC. The NMA was performed for different PET radiopharmaceuticals in both patient- and lesion-based analyses and with a threshold of serum calcitonin or carcinoembryonic antigen (CEA) levels and calcitonin doubling time. The consistency was evaluated by examining the agreement between direct and indirect treatment effects, and publication bias was assessed by funnel plot asymmetry tests. The surface under the cumulative ranking curve values were obtained to calculate the probability of each PET modality being the most effective diagnostic method. Results A total of 306 patients from 14 direct comparison studies using 5 different PET radiopharmaceuticals (18F-FDG, 18F-DOPA, 68Ga-somatostatin analogs, 3-O-methyl-6-[18F]fluoro-DOPA, and 11C-methionine) for the detection of recurrent MTC was included. The detection rate of 18F-DOPA PET was significantly higher than that of FDG PET in both patient- and lesion-based analyses (patient-based analysis: odds ratio, 2.44; 95% confidence interval, 1.4–4.31; lesion-based analysis: odds ratio, 5.74; 95% confidence interval, 1.65–23.4). Among all PET radiopharmaceuticals, 18F-DOPA showed the highest surface under the cumulative ranking curve value in both patient- and lesion-based analyses regardless of serum calcitonin or CEA levels and calcitonin doubling time. Conclusions The results from this NMA indicate that 18F-DOPA PET clearly showed a best performance for the detection of recurrent MTC in both patient- and lesion-based analyses regardless of serum calcitonin or CEA levels and calcitonin doubling time.
Conversion of Mild Cognitive Impairment to Alzheimer Disease in Monolingual and Bilingual Patients

Purpose: Conversion rates from mild cognitive impairment (MCI) to Alzheimer disease (AD) were examined considering bilingualism as a measure of cognitive reserve. Methods: Older adult bilingual (n=75) and monolingual (n=83) patients attending a memory clinic who were diagnosed with MCI were evaluated for conversion to AD. Age of MCI and AD diagnoses and time to convert were recorded and compared across language groups. Patients: Patients were consecutive patients diagnosed with MCI at a hospital memory clinic. Results: Bilingual patients were diagnosed with MCI at a later age than monolingual patients (77.8 and 75.5 y, respectively), a difference that was significant in some analyses. However, bilingual patients converted faster from MCI to AD than monolingual patients (1.8 and 2.8 y, respectively) resulting in no language group difference in age of AD diagnosis. This relationship held after accounting for education, cognitive level, immigration status, and sex. Discussion: The findings suggest that greater cognitive reserve as measured by language status leads to faster conversion between MCI and AD, all else being equal.
Comparison of Rhinoplasty Patients Informed With Standard Verbal Information in Preoperative Period and Rhinoplasty Patients Informed and Treated With Visual Information Through Catalog in Terms of the Development of Agitation, Edema and Ecchymose in the Postoperative Period.

AIM In this study, we aimed to compare the effects of standard verbal information in the preoperative period and the information by visual expression and physical applications in the development of agitation, edema and ecchymosis in the postoperative period. MATERIALS AND METHODS The study was carried out in 60 ASA I-II patients who were going to undergo open rhinoplasty by plastic surgery. In the Preoperative Anesthetic Assessment the patients were divided into two groups as the patients given standard verbal information (Group S; n = 30) and those informed with a catalog which contains visuals (Group V; n = 30) In the preoperative period, anxiety levels of the patients were evaluated. Standard anesthesia induction was performed in both groups after standard monitoring. Patients were monitored in the post-anesthesia care unit and ward. Patient's extubation quality, presence of postoperative agitation and periorbital edema and ecchymosis at the 6th, 12th, 18th, and 24th hours were evaluated. RESULTS No significant difference was found between the groups in terms of intraoperative and postoperative MAP, HR, extubation quality, presence of recovery agitation, postoperative pain, development edema and ecchymosis (P > 0.05). Significant positive correlation was found between post-extubation MAP and edema scores at the 16th and 24th hours postoperatively and between the post-anesthesia care unit entry MAP and ecchymosis at the 24th postoperative hours independently of the groups (r = 0.27; P = 0.038, r = 0.302; P = 0.019, r = 0.345; P = 0.007, respectively). RESULT In our study, it was concluded that detailed visual information and physical application in the preoperative period among rhinoplasty patients had no effect on the incidence of postoperative agitation, development of edema and ecchymosis.
Impulse for animal welfare outside the experiment

Animal welfare is a growing societal concern and the well-being of animals used for experimental purposes is under particular scrutiny. The vast majority of laboratory animals are mice living in small cages that do not offer very much variety. Moreover, the experimental procedure often takes very little time compared to the time these animals have been bred to the desired age or are being held available for animal experimentation. However, for the assessment of animal welfare, the time spent waiting for an experiment or the time spent after finishing an experiment has also to be taken into account. In addition to experimental animals, many additional animals (e.g. for breeding and maintenance of genetic lines, surplus animals) are related to animal experimentation and usually face similar living conditions. Therefore, in terms of improving the overall welfare of laboratory animals, there is not only a need for refinement of experimental conditions but especially for improving living conditions outside the experiment. The improvement of animal welfare thus depends to a large extent on the housing and maintenance conditions of all animals related to experimentation. Given the current state of animal welfare research there is indeed a great potential for improving the overall welfare of laboratory animals.
Synchrony Degree of Dietary Energy and Nitrogen Release Influences Microbial Community, Fermentation, and Protein Synthesis in a Rumen Simulation System

Synchrony of energy and nitrogen release in rumen has been proposed to maximize ruminal microbial fermentation. However, the information regarding bacterial community composition and its metabolism under a higher or lower degree of synchronization is limited. In our study, a 0 to 6 h post-feeding infusion (first half infusion, FHI), 6 to 12 h post-feeding infusion (second half infusion, SHI), and 0 to 12 h post-feeding infusion (continuous infusion, CI) of maltodextrin were used to simulate varying degrees of synchronization of energy and nitrogen release in a rumen simulation system. In addition, the bacterial community, metabolite, enzyme activity, and microbial protein synthesis (MPS) were evaluated. Compared with the FHI and CI, the relative abundance of Fibrobacter, Ruminobacter, BF311, and CF231 decreased in the SHI, but that of Klebsiella and Succinivibrio increased in the SHI. The NH3-N and branched-chain volatile fatty acids were significantly higher, but propionate content and activities of glutamate dehydrogenase (GDH) and alanine dehydrogenase were significantly lower in the SHI than those in the FHI and CI. The SHI had lower MPS and less efficiency of MPS than the FHI and CI, which indicated that the SHI had a lower degree of synchronization. Correlation analysis showed that MPS was positively related to GDH activity and relative abundance of Fibrobacter but negatively related to NH3-N and relative abundance of Klebsiella. Therefore, a higher degree of synchronization of energy and nitrogen release increased MPS partly via influencing the bacterial community, metabolism, and enzyme activities of ammonia assimilation in the in vitro fermenters.
Cutting Edge: Antitumor Immunity by Pathogen-Specific CD8 T Cells in the Absence of Cognate Antigen Recognition

Key Points Pathogen-specific bystander memory CD8 T cells infiltrate tumors in the absence of Ag. 1°M bystander CD8 T cells are relatively inert in the tumor. 4°M bystander cells gain effector functions independent of cognate Ag recognition. Cancer prognosis often correlates with the number of tumor-infiltrating CD8 T cells, but many of these cells recognize pathogens that commonly infect humans. The contribution of pathogen-specific “bystander” CD8 T cells to antitumor immunity remains largely unknown. Inflammatory cytokines are sufficient for memory CD8 T cell activation and gain of effector functions, indicating tumor-derived inflammation could facilitate pathogen-specific CD8 T cells to participate in tumor control. In this study, we show in contrast to tumor-specific CD8 T cells that pathogen-specific primary memory CD8 T cells inside tumor were not able to exert their effector functions and influence tumor progression. However, infection-induced memory CD8 T cells with defined history of repeated Ag encounters (i.e., quaternary memory) showed increased sensitivity to tumor-derived inflammation that resulted in activation, gain of effector functions, and better control of tumor growth. Thus, memory CD8 T cells with heightened ability to recognize environmental inflammatory stimuli can contribute to antitumor immunity in the absence of cognate Ag recognition.
Long-term mortality and causes of death among patients with mild traumatic brain injury: a 5-year multicenter study

ABSTRACT Objective: Undergoing mild traumatic brain injury (mTBI) increases mortality risk, but it is unclear what drives this finding. This study explored associations with mortality in patients with mTBI. Methods: This was a retrospective study of patients with mTBI and controls admitted to six level 1 trauma centers in 1/1/2009-12/31/2013. Mortality data were from the CDC National Death Index. Patients with mTBI were identified by ICD-9 code, Glasgow Coma Scale 13–15, Injury Severity Score (ISS) <16, and loss of consciousness ≤1 hour. Controls had hospital length of stay ≤24 hours, ISS<16, and no head injury. Results: This study included 964 patients with mTBI and 5,567 controls. mTBI was associated with a 47% increased 5-year mortality risk (HR = 1.47, 95% CL 1.08–2.01). Patients with mTBI were more likely to die of a neurodegenerative disease (17% vs 11%, P = .119). Cardiovascular (HR = 1.80, 95% CL 1.17–2.77), neurological (HR = 3.33, 95% CL 2.07–5.38), and respiratory (HR = 1.70, 95% CL 1.01–2.86) comorbidities were associated with mortality in patients with mTBI. Conclusions: Patients with mTBI are at increased mortality risk in the 5 years post-injury. Mortality in patients with mTBI was most influenced by preexisting conditions.
A Protein Epitope Targeted by the Antibody Response to Kawasaki Disease.

BACKGROUND Kawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms and death. Clinical and epidemiologic features implicate an infectious cause, but specific antigenic targets of the disease are unknown. Peripheral blood plasmablasts are normally highly clonally diverse but the antibodies they encode are ~70% antigen-specific 1-2 weeks after infection. METHODS We isolated single peripheral blood plasmablasts from children with KD at 1-3 weeks after onset and prepared 60 monoclonal antibodies (mAbs). We used the mAbs to identify their target antigens and assessed serologic response among KD patients and controls to specific antigen. RESULTS Thirty-two mAbs from 9 of 11 patients recognize antigen within intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells of fatal cases. Five of these mAbs, from 3 patients with coronary aneurysms, recognize a specific peptide, which blocks binding to the inclusion bodies. Sera from 5/8 KD patients at day >8 after illness onset, compared with 0/17 infant controls (p<0.01), recognized the KD peptide antigen. CONCLUSIONS These results identify a protein epitope targeted by the antibody response to KD and provide a means to elucidate the pathogenesis of this important worldwide pediatric problem.
Impact of delayed treatment in women diagnosed with breast cancer: A population‐based study

The impact of timely treatment on breast cancer‐specific survival may differ by tumor stage. We aim to study the impact of delayed first treatment on overall survival across different tumor stages. In addition, we studied the impact of delayed adjuvant treatments on survival in patients with invasive nonmetastatic breast cancer who had surgery ≤90 days postdiagnosis. This population‐based study includes 11 175 breast cancer patients, of whom, 2318 (20.7%) died (median overall survival = 7.9 years). To study the impact of delayed treatment on survival, hazard ratios and corresponding 95% confidence intervals were estimated using Cox proportional‐hazards models. The highest proportion of delayed first treatment (>30 days postdiagnosis) was in patients with noninvasive breast cancer (61%), followed by metastatic breast cancer (50%) and invasive nonmetastatic breast cancer (22%). Delayed first treatment (>90 vs ≤30 days postdiagnosis) was associated with worse overall survival in patients with invasive nonmetastatic (HR: 2.25, 95% CI 1.55‐3.28) and metastatic (HR: 2.09, 95% CI 1.66‐2.64) breast cancer. Delayed adjuvant treatment (>90 vs 31‐60 days postsurgery) was associated with worse survival in patients with invasive nonmetastatic (HR: 1.50, 95% CI 1.29‐1.74). Results for the Cox proportional‐hazards models were similar for breast cancer‐specific death. A longer time to first treatment (31‐90 days postdiagnosis) may be viable for more extensive diagnostic workup and patient‐doctor decision‐making process, without compromising survival. However, patients’ preference and anxiety status need to be considered.
Acute Exposure to Key Aquaculture Environmental Stressors Impaired the Aerobic Metabolism of Carassius auratus gibelio

Carassius auratus gibelio is an omnivore favored for its flavor and is commonly used as a benthic species in traditional pond polyculture. This study investigated the effects of common aquaculture stressors, such as high ammonia, high nitrite, high pH, and hypoxia on the aerobic metabolism of C. auratus gibelio. The results showed that the standard metabolic rate (SMR) was positively correlated with ammonia, nitrite, and pH, while the maximum metabolic rate (MMR) was negatively correlated with all four stressors. Thus, aerobic scope (AS) was reduced when C. auratus gibelio was exposed to high ammonia, high nitrite, high pH, and hypoxia. The peak of post-prandial O2 consumption was positively correlated with nitrite, pH, and the occurrence of the peak metabolic rate post-prandial was delayed in high ammonia, high nitrite, hypoxia, and high pH conditions. These findings indicated that, in experimental conditions, exposure to these environmental stressors can influence aerobic metabolism in C. auratus gibelio. With more energy required to maintain standard metabolic rates, less will be available for growth. While the C. auratus gibelio is one of the most hypoxia tolerance species, the reduction we observed in AS caused by stressors that commonly occur in ponds and in nature will likely affect growth in ponds and fitness in nature. These data have provided insight into the optimal, fitness-maximizing thresholds for these common stressors in this species of interest.
Treatment of conjunctival papilloma with topical interferon alpha-2b - case report

Abstract Rationale: Conjunctival papilloma is a benign neoplastic lesion of epithelial origin, with a minimal tendency toward malignancy and an exophytic growth type. Etiological factors that contribute to the appearance of papilloma are UV exposure, HPV infection, smoking, and immunodeficiency. A case report of limbal conjunctival papilloma treatment with topical interferon alpha-2b eye drops applied to the conjunctival sac. Patient concerns: A 49-year-old female patient treated in the Clinical Department of Ophthalmology for conjunctival lesion located in the temporal quadrant near the limbus of the right eye. Ocular examination of the patient's eye did not show any abnormalities: visual acuity—20/20, intraocular pressure—16 mmHg. Diagnoses: During physical examination, a broad-based pink lesion of size 4 mm × 6 mm was found in interpalpebral bulbar conjunctiva with prominent feeder vessels and soft consistency. Lesion in the biomicroscopic examination did not show any sign of malignancy. In Swept Source Optical Coherence Tomography (SS-OCT) there was no sign of infiltration into sclera or cornea. In vivo confocal microscopy (IVCM) examination, revealed loss of the normal conjunctival epithelium - hyper-reflective cells, variation of cell size. A clinical diagnosis of limbal conjunctival papilloma was made. Interventions: Interferon alpha-2b 1 million IU/ml eye drops were applied 4 times a day for 5 months. The treatment lasted 5 months without changing the dosing regimen. Three months after the start of the interferon treatment, a complete regression of the lesion was achieved. Treatment was continued for the following 2 months. Controlled IVCM after 6 months showed only few hyper-reflective cells and fibrotic tissue. Outcomes: Treatment of conjunctival papilloma with topical interferon alpha-2b led to the complete regression of the lesion. Although after the therapy the conjunctiva appears normal both in slit lamp and in the OCT examination, there is a noticeable fibrosis of the tissue in confocal microscopy. During the 14-month follow-up period, there were no recurrent lesions. Lessons: In this study, topical interferon alpha-2b has been shown to be an effective and safe therapy for small-to-medium-size conjunctival papilloma without any sign of malignancy.
Genetic characteristics of Jiaji Duck by whole genome re-sequencing

Jiaji Duck (JJ) is a Muscovy duck species that possesses many superior characteristics, and it has become an important genetic resource in China. However, to date, its genetic characteristics and genetic relationship with other duck breeds have not been explored yet, which greatly limits the utilization of JJ. In the present study, we investigated the genome sequences of 15 individual ducks representing five different duck populations, including JJ, French Muscovy duck (FF), mallard (YD), hong duck (HD) and Beijing duck (BD). Moreover, we investigated the characteristics of JJ-specific single nucleotide polymorphisms (SNPs) and compared the genome sequences of JJ vs. YD and JJ vs. BD using integrated strategies, including mutation detection, selective screening, and Gene Ontology (GO) analysis. More than 40 Gb of clean data were obtained for each population (mean coverage of 13.46 Gb per individual). A total number of 22,481,367 SNPs and 4,156,829 small insertion-deletions (Indels) were identified for the five duck populations, which could be used as molecular markers in breeding and utilization of JJ. Moreover, we identified 1,447,932 JJ-specific SNPs, and found that genes covering at least one JJ-specific SNP mainly involved in protein phosphorylation and dephosphorylation, as well as DNA modification. Phylogenetic tree and principal components analysis (PCA) revealed that the genetic relationship of JJ was closest to FF, while it was farthest to BD. A total of 120 and 111 genes were identified as positive selection genes for JJ vs. BD and JJ vs. YD, respectively. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the positive selection genes for JJ vs. BD ducks mainly involved in pigmentation, muscle contraction and stretch, gland secretion, and immunology, while the positive selection genes obtained from JJ vs. YD ducks mainly involved in embryo development, muscle contraction and stretch, and gland secretion. Taken together, our findings enabled us to better understand the characteristics of JJ and provided a molecular basis for the breeding and hybrid utilization of JJ in the future.
Men’s Reflections on Postsuicide Attempt Episode in Bangladesh

This is the first ever research in Bangladesh that provides understanding about men’s postsuicide attempt reflections from a district called Jhenaidah which is assumed to be a high suicide-prone area in the country. Employing qualitative semistructured interviews with 17 men who have attempted suicide, aged 18 years and older, this research finds the survivors encountered several immediate reactions from others specifically targeting toward demeaning their masculinity. Nonetheless, they adopted several means to cope with the postsuicide episode that are thematically arranged as self-deprecation, rebuilding oneself, revenge vis-à-vis forgiveness, and impulses to escape vis-à-vis nonreactive. The postattempt episodes of the survivors are likely to be moved toward further risk factors. Therefore, it is important to take protective measures for the survivors. Specific to this district, developing a context-specific suicide prevention model, targeting the risk population could be a possible solution to the problems associated with the postattempt episodes.