Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunopathogenesis of canine chronic ulcerative stomatitis

Canine Chronic Ulcerative Stomatitis is a spontaneously occurring inflammatory disease of the oral mucosa. An immune-mediated pathogenesis is suspected though not yet proven. We have recently reported on the clinical and histologic features, and identification of select leukocyte cell populations within the lesion. A clinical and histologic similarity to oral lichen planus of people was proposed. In the present study, these initial observations are extended by examining lesions from 24 dogs with clinical evidence of chronic ulcerative stomatitis. Because dogs with chronic ulcerative stomatitis often have concurrent periodontal disease, we wondered if dental plaque/biofilm may be a common instigator of inflammation in both lesions. We hypothesized that dogs with chronic ulcerative stomatitis would exhibit a spectrum of pathologic changes and phenotype of infiltrating leukocytes that would inform lesion pathogenesis and that these changes would differ from inflammatory phenotypes in periodontitis. Previously we identified chronic ulcerative stomatitis lesions to be rich in FoxP3+ and IL17+ cells. As such, we suspect that these leukocytes play an important role in lesion pathogenesis. The current study confirms the presence of moderate to large numbers of FoxP3+ T cells and IL17+ cells in all ulcerative stomatitis lesions using confocal immunofluorescence. Interestingly, the majority of IL17+ cells were determined to be non-T cells and IL17+ cell frequencies were negatively correlated with severity on the clinical scoring system. Three histologic subtypes of ulcerative stomatitis were determined; lichenoid, deep stomatitis and granulomatous. Periodontitis lesions, like stomatitis lesions, were B cell and plasma cell rich, but otherwise differed from the stomatitis lesions. Direct immunofluorescence results did not support an autoantibody-mediated autoimmune disease process. This investigation contributes to the body of literature regarding leukocyte involvement in canine idiopathic inflammatory disease pathogenesis.
Polygenic impact of morningness on the overnight dynamics of sleep spindle amplitude

Sleep spindles are thalamocortical oscillations that contribute to sleep maintenance and sleep‐related brain plasticity. The current study is an explorative study of the circadian dynamics of sleep spindles in relation to a polygenic score (PGS) for circadian preference towards morningness. The participants represent the 17‐year follow‐up of a birth cohort having both genome‐wide data and an ambulatory sleep electroencephalography measurement available ( N = 154, Mean age = 16.9, SD = 0.1 years, 57% girls). Based on a recent genome‐wide association study, we calculated a PGS for circadian preference towards morningness across the whole genome, including 354 single‐nucleotide polymorphisms. Stage 2 slow (9‐12.5 Hz, N = 186 739) and fast (12.5‐16 Hz, N = 135 504) sleep spindles were detected using an automated algorithm with individual time tags and amplitudes for each spindle. There was a significant interaction of PGS for morningness and timing of sleep spindles across the night. These growth curve models showed a curvilinear trajectory of spindle amplitudes: those with a higher PGS for morningness showed higher slow spindle amplitudes in frontal derivations, and a faster dissipation of spindle amplitude in central derivations. Overall, the findings provide new evidence on how individual sleep spindle trajectories are influenced by genetic factors associated with circadian type. The finding may lead to new hypotheses on the associations previously observed between circadian types, psychiatric problems and spindle activity.
Reading in the presence of macular disease: a mini‐review

Reading is vital to full participation in modern society. To millions of people suffering from macular disease that results in a central scotoma, reading is difficult and inefficient, rendering reading as the primary goal for most patients seeking low vision rehabilitation. The goals of this review paper are to summarize the dependence of reading speed on several key visual and typographical factors and the current methods or technologies for improving reading performance for people with macular disease.
Narratives of childless widows: exploring the lived experiences and well-being of childless widows in rural Nigeria

ABSTRACT Background: Widows are socioeconomically disadvantaged, especially in low resource regions. Childless widows are a group whose plight may be worse given sociocultural circumstances. In the current study, we examined the lived experiences of childless widows living in remote Nigeria, highlighting this group as being in critical need for social interventions. Method: Childless widows (n = 11) in rural settings in South East Nigeria were interviewed. Narrative analysis was used in navigating the lived experiences of the widows. Results: Extreme distress, ostracism, stigma, and traumatic experiences were common in the narratives of the widows. However, childlessness was at the core of their distress. Treated as outcasts, the widows resigned to God, though some were scarcely allowed to play supportive roles among relatives. As social welfare packages are almost non-existent in this region, religious groups often played supportive roles. Conclusion: Legislation protecting widows are good but may not be sufficient if it does not translate to improved wellbeing/welfare for widows. Childless widows, especially those in rural areas, are especially vulnerable as they face peculiar deprivation and psychological distress arising from cultural/social realities. Recognising the limited resources in low income countries, mobilisation of local structures and resources to educate and monitor local communities are important.
Disruption in daily eating-fasting and activity-rest cycles in Indian adolescents attending school

A lifestyle with erratic eating patterns and habits predisposes youngsters to obesity. Through a two-phase feasibility study among Indian students living in the Delhi area, we longitudinally examined the following: (1) the daily eating-fasting cycles of students (N = 34) in school and college using smartphones as they transition from high school (aged 13–15 years; nIX = 13) to higher secondary school (HSSS; 16–18 years; nXII = 9) to their first year (FY) of college (18–19 years; nFC = 12); and (2) daily activity-rest cycles and light-dark exposure of 31 higher secondary school students (HSSS) using actigraphy. In phase 1, students’ food data were analyzed for temporal details of eating events and observable differences in diet composition, such as an energy-dense diet (fast food (FF)), as confounding factors of circadian health. Overall, the mean eating duration in high school, higher secondary and FY college students ranged from 14.1 to 16.2h. HSSS exhibited the shortest night fasting. Although FY college students exhibited the highest fast food percentage (FF%), a positive correlation between body mass index (BMI) and FF% was observed only among HSSS. Furthermore, the body weight of HSSS was significantly higher, indicating that FF, untimely eating and reduced night fasting were important obesity-associated factors in adolescents. Reduced night fasting duration was also related to shorter sleep in HSSS. Therefore, food data were supplemented with wrist actigraphy, i.e., activity-rest data, in HSSS. Actigraphy externally validated the increased obesogenic consequences of deregulated eating rhythms in HSSS. CamNtech motion watches were used to assess the relationship between disturbed activity cycles of HSSS and other circadian clock-related rhythms, such as sleep. Less than 50% of Indian HSSS slept 6 hours or more per night. Seven of 31 students remained awake throughout the night, during which they had more than 20% of their daily light exposure. Three nonparametric circadian rhythm analysis (NPCRA) variables revealed circadian disruption of activity in HSSS. The present study suggests that inappropriate timing and quality of food and sleep disturbances are important determinants of circadian disruptions in adolescents attending school.
Characteristics and outcome of AKT1 E17K-mutant breast cancer defined through AACR GENIE, a clinicogenomic registry.

AKT inhibitors have promising activity in AKT1 E17K-mutant estrogen receptor (ER)-positive metastatic breast cancer, but the natural history of this rare genomic subtype remains unknown. Utilizing AACR Project GENIE, an international clinicogenomic data-sharing consortium, we conducted a comparative analysis of clinical outcomes of matched AKT1 E17K-mutant (n=153) and -wildtype (n=302) metastatic breast cancer patients. AKT1-mutant cases had similar adjusted overall survival (OS) compared with AKT1-wildtype controls (median OS, 24.1 vs 29.9, respectively; p=0.98). AKT1-mutant cases enjoyed longer durations on mTOR inhibitor therapy, an observation previously unrecognized in pivotal clinical trials due to the rarity of this alteration. Other baseline clinicopathologic features, as well as durations on other classes of therapy were broadly similar. In summary, we demonstrate the feasibility of using a novel and publicly accessible clincogenomic registry to define outcomes in a rare genomically defined cancer subtype, an approach with broad applicability to precision oncology.
An Integrated Infant and Young Child Feeding and Micronutrient Powder Intervention Does Not Affect Anemia, Iron Status, or Vitamin A Status among Children Aged 12-23 Months in Eastern Uganda.

BACKGROUND Micronutrient powders (MNP) can reduce iron deficiency and anemia in children. OBJECTIVE We evaluated the impact of an integrated infant and young child feeding (IYCF)-MNP intervention on anemia and micronutrient status among children aged 12-23 mo in Eastern Uganda. The intervention focused on MNP distribution, IYCF education, and caregiver behavior change. METHODS Population-based cross-sectional surveys representative of children aged 12-23 mo in Amuria (intervention) and Soroti (nonintervention) districts were collected in June/July 2015 at baseline (n = 1260) and 12 mo after implementation at endline in 2016 (n = 1490). From pooled capillary blood, we assessed hemoglobin, malaria, ferritin, retinol binding protein (RBP), C-reactive protein, and ɑ1-acid glycoprotein. Ferritin and RBP were regression-adjusted to correct for inflammation. Caregivers reported sociodemographic characteristics and MNP knowledge and practices. Linear regression estimated the difference-in-difference (DiD) effect of MNP on hemoglobin, ferritin, and RBP, and logistic regression estimated DiD effect of MNP on anemia (hemoglobin <11.0 g/dL), iron deficiency (ferritin <12.0 µg/L), iron deficiency anemia (hemoglobin <11.0 g/dL and ferritin <12.0 µg/L), and vitamin A deficiency (VAD; RBP equivalent to <0.70 µmol/L retinol: <0.79 µmol/L at baseline and RBP <0.67 µmol/L at endline). RESULTS In Amuria, 96% of children had ever consumed MNP versus <1% of children in Soroti. Fifty-four percent of caregivers reported organoleptic changes when MNP were added to foods cooked with soda ash. Adjusting for age, sex, malaria, recent morbidity, and household-level factors, the intervention was associated with -0.83 g/dL lower hemoglobin (95% CI, -1.36, -0.30 g/dL; P = 0.003) but not with anemia, ferritin, iron deficiency, iron deficiency anemia, RBP, or VAD. CONCLUSIONS Despite high program fidelity, the intervention was associated with reduced hemoglobin concentrations but not with change in anemia or micronutrient status among children aged 12-23 mo in Eastern Uganda. Contextual factors, such as cooking with soda ash, might explain the lack of effectiveness.
Ovarian Stimulation Is Safe and Effective for Patients with Gynecologic Cancer.

Purpose: To compare long-term outcomes of gynecologic cancer patients who pursued controlled ovarian hyperstimulation (COH) for fertility preservation (FP) with those who did not. Methods: Retrospective cohort, COH, and health outcomes in gynecologic cancer patients; data were analyzed by chi-square test, t-tests, and logistic regression. Results: Ninety patients with a gynecologic malignancy contacted the FP patient navigator: 45.6% (n = 41) had ovarian cancer, 25.6% (n = 23) endometrial cancer, 18.9% (n = 17) cervical cancer, 5.6% (n = 5) uterine cancer, and 4.4% (n = 4) multiple gynecologic cancers. From this cohort, 32 underwent COH, 43 did not, and 18 pursued ovarian tissue cryopreservation (OTC; 3 patients had both COH and OTC). Median age and type of cancer were not significantly different between the groups. COH patients had a range of 1-35 oocytes retrieved. Days to next cancer treatment in the COH group was 36 days; for those who declined COH, it was 22 days (not significant [NS], p > 0.05). There were two recurrences reported in the stimulation group and four in the no stimulation group (NS). Five deaths were reported, two in the stimulation group, none in the no stimulation group, and three in the OTC group (NS); 34% (n = 11) COH patients returned to use cryopreserved specimens, of which 45% (n = 5) had a live birth. Conclusion: Although time to next treatment was longer in the group of patients who underwent COH, this did not reach statistical significance. It appears that in selected patients with GYN malignancies, COH for oocyte or embryo cryopreservation is safe, with reasonable stimulation outcomes and no difference in long-term outcomes.
Missing regions within the molecular architecture of human fibrin clots structurally resolved by XL-MS and integrative structural modeling

Significance Fibrinogen hexamers are major components of blood clots. After release of fibrinopeptides resulting in fibrin monomers, clot formation occurs through fibrin oligomerization followed by lateral aggregation, packing into fibrin fibers, and consequent branching. Shedding light on fibrin clots by in situ cross-linking mass spectrometry and structural modeling extends our current knowledge of the structure of fibrin with regard to receptor-binding hotspots. Further restraint-driven molecular docking reveals how fibrin oligomers laterally aggregate into clots and uncovers the molecular architecture of the clot to albumin interaction. We hypothesize this interaction is involved in the prevention of clot degradation. Mapping known mutations validates the generated structural model and, for a subset, brings their molecular mechanisms into view. Upon activation, fibrinogen forms large fibrin biopolymers that coalesce into clots which assist in wound healing. Limited insights into their molecular architecture, due to the sheer size and the insoluble character of fibrin clots, have restricted our ability to develop novel treatments for clotting diseases. The, so far resolved, disparate structural details have provided insights into linear elongation; however, molecular details like the C-terminal domain of the α-chain, the heparin-binding domain on the β-chain, and other functional domains remain elusive. To illuminate these dark areas, we applied cross-linking mass spectrometry (XL-MS) to obtain biochemical evidence in the form of over 300 distance constraints and combined this with structural modeling. These restraints additionally define the interaction network of the clots and provide molecular details for the interaction with human serum albumin (HSA). We were able to construct the structural models of the fibrinogen α-chain (excluding two highly flexible regions) and the N termini of the β-chain, confirm these models with known structural arrangements, and map how the structure laterally aggregates to form intricate lattices together with the γ-chain. We validate the final model by mapping mutations leading to impaired clot formation. From a list of 22 mutations, we uncovered structural features for all, including a crucial role for βArg’169 (UniProt: 196) in lateral aggregation. The resulting model can potentially serve for research on dysfibrinogenemia and amyloidosis as it provides insights into the molecular mechanisms of thrombosis and bleeding disorders related to fibrinogen variants. The structure is provided in the PDB-DEV repository (PDBDEV_00000030).
The expression of tissue inhibitors of metalloproteinase-2 (TIMP-2) in epithelial serous ovarian tumors

Objective：Tissue inhibitors of metalloproteinases (TIMPs) play a key role in maintaining homeostasis of the extracellular matrix (ECM) by controlling matrix metalloproteinases (MMPs). In addition to their role in regulating MMPs, TIMPs have also been shown to have pluripotential effects on cell growth, apoptosis and differentiation. The aim of this study was to examine TIMP-2 level in serous ovarian tumor tissues and to understand further the role of TIMP-2 protein in ovarian tumorigenesis. Methods：Expression of TIMP-2 was assessed by immunohistochemistry in a total of 57 ovarian specimens including five normal ovaries, 12 benign serous cystadenomas, 20 serous borderline tumors and 20 serous carcinomas. Results：The present study found that TIMP-2 immunostaining was significantly more frequent in serous carcinomas, mainly in tumor epithelium, compared with cells of the other tissues studied. Conclusion：TIMP-2 in serous ovarian carcinoma may function to favor tumor growth in serous ovarian tumorigenesis. Additional research is now needed to elucidate further the role of TIMP-2 in the biological behavior of ovarian serous tumors.
The Impact of the ITI International Team for Implantology on Implant Dentistry: A Retrospective and Descriptive Analysis of 30 Years of Research Support.

PURPOSE The purpose of this study was to analyze the projects submitted to the ITI International Team for Implantology for funding and the scientific publications ensuing from these projects, over a period of 30 years. MATERIALS AND METHODS This analysis was performed based on information available in the database of the ITI. For each project, data related to institution, country of origin, and grant status (financed or rejected) were extracted. For the financed projects, the grant amount and number of publications were recorded. Publications were searched independently by two investigators. For all publications, the study topic, study design, and citation number were recorded. RESULTS From a total of 1,372 submitted projects from 51 different countries and 308 different institutions, 514 (37.46%) were financed by the ITI. This amounts to more than CHF 52 million invested in favor of implant dentistry and related fields. A total of 552 publications (including original research and reviews) were identified related to these projects, with the majority being in vitro studies (n = 198), and the most common topic researched was implant surface modification (n = 134). The United States was the country and the University of Bern was the institution with the largest number of financed projects and published papers. CONCLUSION This analysis revealed that the ITI has been actively supporting research in the field of implant dentistry and related areas globally. Several concepts in present-day implantology are based on literature from ITI-funded projects.
Influence of Facial Bone Thickness After Implant Placement into the Healed Ridges on the Remodeled Facial Bone and Considering Soft Tissue Recession: A Systematic Review.

PURPOSE A systematic review was performed of the dimensional changes in facial cortical bone following implant placement into healed ridges, with the aim of establishing a minimum bone thickness that limits such changes. The influence of such bone remodeling upon the soft tissues and implant survival was also evaluated. MATERIALS AND METHODS A search was done of two electronic databases (MEDLINE via PubMed and CENTRAL), complemented by a manual search and lists of references. The risk of bias and methodological quality were assessed using the Cochrane Collaboration tool, the Methodological Index for Non-randomized Studies (MINORS), and the Quality Appraisal Checklist for Case Series. RESULTS The search yielded 536 publications, of which 11 (four randomized clinical trials, two non-randomized clinical trials, and five case series) were entered in the review. All the included studies reported vertical and horizontal implant facial bone resorption. Decreased facial bone thickness was correlated with increased vertical bone resorption, which in turn was associated with slight soft tissue retraction. A meta-analysis could not be performed, due to the heterogeneity of the study designs and measurement sites. CONCLUSION No minimum facial bone thickness was seen that would completely avoid peri-implant bone loss and maintain soft tissue stability. However, a thickness of approximately 2 mm was associated with diminished vertical bone resorption and less peri-implant mucosal recession.
T cell epitope mapping of secukinumab and ixekizumab in healthy donors

ABSTRACT Secukinumab, a human monoclonal antibody that selectively neutralizes IL-17A, has consistently shown low anti-drug antibody responses in patients with psoriasis, psoriatic arthritis, and ankylosing spondylitis. Secukinumab has also shown lower in vitro immunogenicity potential compared with other monoclonal antibodies used to treat psoriasis and psoriatic arthritis, and a significantly lower in vitro T cell precursor frequency compared with ixekizumab, which targets the same antigen. Here, secukinumab and ixekizumab were further examined regarding their specific T cell epitopes. Secukinumab- or ixekizumab-specific CD4 T cell lines were generated from 31 healthy, treatment-naïve donors via 28-day co-culture with mature monocyte-derived dendritic cells exposed to either antibody. Consistent with previous data, the frequency of preexisting T cells to secukinumab was significantly lower as compared with ixekizumab. Only two T cell lines from two different donors could be derived for secukinumab, but no specific T cell epitope was identified. In contrast, 32 T cell lines from eight donors were obtained for ixekizumab. For 11 of these T cell lines, the specific T cell epitopes could be identified and confirmed by major histocompatibility complex–associated peptide proteomics as being naturally presented peptides. All identified T cell epitopes cluster in four main regions that are overlapping with the complementarity-determining regions HCDR3, LCDR1, LCDR2 and LCDR3. Interestingly, ixekizumab CDRs contain amino acids that are not found in any of the germline family members. These amino acids may be associated with the higher number of T cell epitopes identified for ixekizumab light chain and may contribute to the increased in vitro immunogenicity potential observed for ixekizumab vs. secukinumab.