Miracle-dz/UniFAR-FTUs huggingface dataset:
Localization and Likelihood of Chondral and Osteochondral Lesions After Patellar Dislocation in Surgically Treated Children and Adolescents

Background: Patellar dislocation is a common injury in children and adolescents. There is a lack of information about concomitant osteochondral lesions in these patients. Hypothesis: We hypothesized that the likelihood of chondral or osteochondral lesions would increase with each prior patellar dislocation and that the appearance of lesions in surgically treated children and adolescents would be influenced by age, sex, injury mechanism, and body mass index (BMI). Study Design: Case-control study; Level of evidence, 3. Methods: Inclusion criteria were (1) age <18 years, (2) surgical treatment with diagnostic arthroscopy of the knee including description of chondral and osteochondral lesions, and (3) maximum time period between the last patellar dislocation and presentation in our department of 6 weeks and maximum of 4 weeks between presentation and surgery. A total of 153 children (173 knees) with a mean age of 13.0 ± 2.1 years were included. All surgical reports and intraoperative arthroscopic imaging were analyzed retrospectively for the location and severity of lesions. The likelihood of lesions was calculated with multiple stepwise regression models regarding injury mechanism, number of dislocations, sex, age, physeal closure, and BMI. Results: The regression model to predict femoral lesions was statistically significant (χ2[5] = 26.55; P < .001) and identified male sex, BMI ≥25, traumatic injury mechanism, and physeal closure as independent factors associated with the appearance of femoral lesions. The second regression model predicting the appearance of patellar lesions was also statistically significant (χ2[4] = 26.07; P < .001) and identified the traumatic injury mechanism as a single independent predictor for patellar lesions. Conclusion: BMI ≥25, male sex, and physeal closure were factors significantly associated with femoral chondral and osteochondral lesions in our cohort. In case of traumatic lateral patellar dislocation (LPD), the likelihood of patellar and femoral chondral and osteochondral lesions is significantly higher than in nontraumatic LPD. Early magnetic resonance imaging and surgical treatment should be considered in obese patients, male patients, and patients with physeal closure and after traumatic LPD.
Bridging the gap between biophysical and social vulnerability in rural India: a community livelihood vulnerability approach

ABSTRACT This study of the nature and extent of livelihood vulnerability of farm households in the Bundelkhand region of Uttar Pradesh, India, involved the computation of livelihood vulnerability indices and indices of exposure, sensitivity and adaptive capacity for different social communities. The empirical findings reveal that farmers belonging to Scheduled Tribes (ST) communities were relatively highly exposed and sensitive to climate change and least able to adapt. In this light, several policy recommendations are proposed to improve the livelihood security of vulnerable groups.
Safety and security of women and girls in public transport

ABSTRACT Violence against women and girls is a major public problem globally. This study had conducted to assess women and girls safety and security in public transport and identify factors contributing to violence in Hawassa city, Ethiopia. Data used in the study have been obtained from 199 randomly selected respondents (36.7% women and 63.3% girls), and in addition, 24 focus group discussion members have also participated. Binary Logistic Regression had employed for quantitative data analysis. Data from focus group discussions were analyzed qualitatively using narrative analysis. The types of violence identified were physical, sexual, and psychological. The finding shows that 50.8% of women and girls have experienced more than one type of violence while using public transport. The results indicated that six variables significantly contributed to violence. These variables were age, marital status, type of public transport used, travel time, facilities, and management of public transport services. The result indicates that violence against women and girls in public transport is a serious threat to women’s safety and security to access their mobility in the city. Therefore, cities must focus on developing gender-sensitive public transport service plans and policies that consider women and girls unique needs in public transportation.
Gravity Wave Characteristics in the Southern Hemisphere Revealed by a High-Resolution Middle-Atmosphere General Circulation Model

AbstractGravity wave characteristics in the middle- to high-latitude Southern Hemisphere are analyzed using simulation data over 3 yr from a high-resolution middle-atmosphere general circulation model without using any gravity wave parameterizations. Gravity waves have large amplitudes in winter and are mainly distributed in the region surrounding the polar vortex in the middle and upper stratosphere, while the gravity wave energy is generally weak in summer. The wave energy distribution in winter is not zonally uniform, but it is large leeward of the southern Andes and Antarctic Peninsula. Linear theory in the three-dimensional framework indicates that orographic gravity waves are advected leeward significantly by the mean wind component perpendicular to the wavenumber vector. Results of ray-tracing and cross-correlation analyses are consistent with this theoretical expectation. The leeward energy propagation extends to several thousand kilometers, which explains part of the gravity wave distribution aro.
Combined effect of brine salting and high-hydrostatic-pressure processing to improve the microbial quality and physicochemical properties of milkfish fillet

ABSTRACT The effects of soaking milkfish fillet in 3% or 9% NaCl brines for 90 min at 4°C, and followed by processing with varying hydrostatic pressures (300, 400, 500, and 600 MPa) for 5 min on microbial quality and physicochemical properties were evaluated. After brine salting, the color of the fillet, the L* (lightness), W (whiteness), and ΔE (color difference) values increased with the increases in pressure, whereas the a* (redness) and b* (yellowness) values decreased, indicating that the fillet became brighter and whiter. Among them, 3% brine salting combined with pressures of 300 and 400 MPa groups had higher redness (a* value) and lower ΔE value compared to the higher pressure groups. Regarding the texture of the fillet, the hardness and chewiness of unsalted fish were significantly higher than that of brine salted fish under the same pressure, whereas the cohesiveness of the unsalted fillet was significantly lower than that of brine salted fillet. The results indicates that brine salting could make the instrumental texture of fish softer, which can compensate for the disadvantages of increased hardness and chewiness of the fillet caused by high-pressure processing. Brine salting combined with high pressure produced a significantly reducing effect on aerobic plate count (APC), psychrotrophic bacteria count (PBC), and total volatile basic nitrogen (TVBN) values of the fish as compared with that by brine salting or high pressure alone. Therefore, brine salting at a proper brine concentration (3%) and followed by high-pressure processing at 300 or 400 MPa for 5 min can improve or maintain a relatively good color and texture, as well as result in a synergistic bactericidal effect.
Origin and Evolution of Pseudomurein Biosynthetic Gene Clusters

The peptidoglycan (PG; or murein) is a mesh-like structure, which is made of glycan polymers connected by short peptides and surrounds the cell membrane of nearly all bacterial species. In contrast, there is no PG counterpart that would be universally found in Archaea, but rather various polymers that are specific to some lineages. Methanopyrales and Methanobacteriales are two orders of Euryarchaeota that harbor pseudomurein (PM) in their cell-wall, a structural analogue of the bacterial PG. Owing to the differences between PG and PM biosynthesis, some have argued that the origin of both polymers is not connected. However, recents studies have revealed that the genomes of PM-containing Archaea encode homologues of the bacterial genes involved in PG biosynthesis, even though neither their specific functions nor the relationships within the corresponding inter-domain phylogenies have been investigated so far. In this work, we devised a bioinformatic pipeline to identify all potential proteins for PM biosynthesis in Archaea without relying on a candidate gene approach. After an in silico characterization of their functional domains, the taxonomic distribution and evolutionary relationships of the collected proteins were studied in detail in Archaea and Bacteria through HMM similarity searches and phylogenetic inference of the Mur domain-containing family, the ATP-grasp superfamily and the MraY-like family. Our results notably show that the extant archaeal muramyl ligases are ultimately of bacterial origin, but likely diversified through a mixture of horizontal gene transfer and gene duplication. Moreover, structural modeling of these enzymes allowed us to propose a tentative function for each of them in pentapeptide elongation. While our work clarifies the genetic determinants behind PM biosynthesis in Archaea, it also raises the question of the architecture of the cell wall in the last universal common ancestor.
Repurposing Vanoxerine as a new antimycobacterial drug and its impact on the mycobacterial membrane

Mycobacterium tuberculosis is a deadly pathogen, currently the leading cause of death worldwide from a single infectious agent through tuberculosis infections. If the End TB 2030 strategy is to be achieved, additional drugs need to be identified and made available to supplement the current treatment regimen. In addition, drug resistance is a growing issue, leading to significantly lower treatment success rates, necessitating further drug development. Vanoxerine (GBR12909), a dopamine re-uptake inhibitor, was recently identified as having anti-mycobacterial activity. Repurposing vanoxerine or its analogues to treat tuberculosis infections may allow a faster route to clinical use than novel drug discovery. However, its effects on Mycobacteria were not well characterised. Herein, we report vanoxerine as a disruptor of the membrane potential, inhibiting mycobacterial efflux and survival, with an undetectable level of resistance. This study suggests a mechanism of action for vanoxerine, which will allow for its continued development and optimisation for pre-clinical testing.
Performance modulations phase-locked to action depend on internal state

Several studies have probed perceptual performance at different times after a self-paced motor action and found frequency-specific modulations of perceptual performance phase-locked to the action. Such action-related modulation has been reported for various frequencies and modulation strengths. In an attempt to establish a basic effect at the population level, we had a relatively large number of participants (n=50) perform a self-paced button press followed by a detection task at threshold, and we applied both fixed- and random-effects tests. The combined data of all trials and participants surprisingly did not show any significant action-related modulation. However, based on previous studies, we explored the possibility that such modulation depends on the participant’s internal state. Indeed, when we split trials based on performance in neighboring trials, then trials in periods of low performance showed an action-related modulation at ≈17 Hz. When we split trials based on the performance in the preceding trial, we found that trials following a “miss” showed an action-related modulation at ≈17 Hz. Finally, when we split participants based on their false-alarm rate, we found that participants with no false alarms showed an action-related modulation at ≈17 Hz. All these effects were significant in random-effects tests, supporting an inference on the population. Together, these findings indicate that action-related modulations are not always detectable. However, the results suggest that specific internal states such as lower attentional engagement and/or higher decision criterion are characterized by a modulation in the beta-frequency range.
Chromosome-level, nanopore-only genome and allele-specific DNA methylation of Pallas's cat, Otocolobus manul

Pallas’s cat, or the manul cat (Otocolobus manul), is a small felid native to the grasslands and steppes of central Asia. Population strongholds in Mongolia and China face growing challenges from climate change, habitat fragmentation, poaching, and other sources. These threats, combined with O. manul’s zoo collection popularity and value in evolutionary biology, necessitate improvement of species genomic resources. We used standalone nanopore sequencing to assemble a 2.5 Gb, 61-contig nuclear assembly and 17,097 bp mitogenome for O. manul. The primary nuclear assembly had 56x sequencing coverage, a contig N50 of 118 Mb, and a 94.7% BUSCO completeness score for Carnivora-specific genes. High genome collinearity within Felidae permitted alignment-based scaffolding onto the fishing cat (Prionailurus viverrinus) reference genome. Manul contigs spanned all 19 felid chromosomes with an inferred total gap length of less than 400 kilobases. Modified basecalling and variant phasing produced an alternate pseudohaplotype assembly and allele-specific DNA methylation calls; sixty-one differentially methylated regions were identified between haplotypes. Nearest features included classical imprinted genes, non-coding RNAs, and putative novel imprinted loci. The assembled mitogenome successfully resolved existing discordance between Felinae nuclear and mtDNA phylogenies. All assembly drafts were generated from 158 Gb of sequence using seven minION flow cells.
Regulation of replicative histone RNA metabolism by the histone chaperone ASF1

In S phase, duplication and assembly of the whole genome into chromatin requires upregulation of replicative histone gene expression. Here, we explored a potential role of histone chaperones in this process thereby linking chromatin assembly with histone production in human cells. Depletion of the ASF1 chaperone specifically decreased the pool of replicative histones both at the levels of soluble protein and total RNA, while depletion of CAF-1 did not. Most replicative histone genes decreased in their overall expression as revealed by total RNA-seq. In contrast, both their newly synthesized RNAs and nascent RNAs at transcription sites increased as shown by 4sU-labeled RNA-seq and single-molecule RNA FISH, respectively. Further inspection of the sequences corresponding to replicative histone RNAs showed a 3’ processing defect, leading to unprocessed transcripts usually targeted for degradation. We discuss how this regulation of replicative histone RNA metabolism by ASF1 fine-tunes the histone dosage to avoid unbalanced situations deleterious for cell survival.
Despite Impaired Binocular Function, Binocular Disparity Integration Across the Visual Field Is Spared in Normal Aging and Glaucoma

Objective To examine how binocularly asymmetric glaucomatous visual field damage affects processing of binocular disparity across the visual field. Design Case–control study. Participants and Controls A sample of 18 patients with primary open-angle glaucoma, 16 age-matched controls, and 13 young controls. Methods Participants underwent standard clinical assessments of binocular visual acuity, binocular contrast sensitivity, stereoacuity, and perimetry. We employed a previously validated psychophysical procedure to measure how sensitivity to binocular disparity varied across spatial frequencies and visual field sectors, i.e. with full-field stimuli spanning the central 21° of the visual field, and with stimuli restricted to annular regions spanning 0°-3°, 3°-9° or 9°-21°. Main Outcome Measures We verified the presence of binocularly asymmetric glaucomatous visual field damage by comparing—between the two eyes— the mean deviation values obtained from the Humphrey Field Analyzer (HFA) 24-2 test. To assess the spatial-frequency tuning of disparity sensitivity across the visual field of patients and controls, we fit disparity sensitivity data to log-parabola models and compared fitted model parameters. Lastly, we employed disparity sensitivity measurements from restricted visual field conditions to model different possible scenarios regarding how disparity information is combined across visual field sectors. We adjudicated between the potential mechanisms by comparing model predictions to the observed patterns of disparity sensitivity with full-field stimuli. Results The interocular difference in HFA 24-2 mean deviation was greater in glaucoma patients compared to both young and age-matched controls (ps=.01). Across participant groups foveal regions preferentially processed disparities at finer spatial scales, whereas periphery regions were tuned for coarser scales (p<.001). Disparity sensitivity also decreased from the fovea to the periphery (p<.001) and across participant groups (ps<.01). Finally, similar to controls, glaucoma patients exhibited near-optimal disparity integration, specifically at low spatial frequencies (p<.001). Conclusions Contrary to the conventional view that glaucoma spares central vision, we find that glaucomatous damage causes a widespread loss of disparity sensitivity across both foveal and peripheral regions. Despite these losses, cortical integration mechanisms appear to be well preserved, suggesting that glaucoma patients make the best possible use of their remaining binocular function.
Experience Adaptively Tunes the Timing Rules for Associative Plasticity

A key function of the brain is to learn about the statistical relationships between events in the world. A mechanism of this learning is associative neural plasticity, controlled by the timing between neural events. Here, we show that experience can dramatically alter the timing rules governing associative plasticity to match the constraints of a particular circuit and behavior, thereby improving learning. In normal mice, the timing requirements for associative plasticity in the oculomotor cerebellum are precisely matched to the 120 ms delay for visual feedback about behavioral errors.1 This task-specific specialization of the timing rules for plasticity is acquired through experience; in dark-reared mice that had never experienced visual feedback about oculomotor errors, plasticity defaulted to a coincidence-based rule. Computational modeling suggests two broad strategies for implementing this Adaptive Tuning of the Timing Rules for Associative Plasticity (ATTRAP), which tune plasticity to different features of the statistics of neural activity. The modeling predicts a critical role of this process in optimizing the accuracy of temporal credit assignment during learning; consistent with this, behavioral experiments revealed a delay in the timing of learned eye movements in mice lacking experience-dependent tuning of the timing rules for plasticity. ATTRAP provides a powerful mechanism for matching the timing contingencies for associative plasticity to the functional requirements of a particular circuit and learning task, thereby providing a candidate neural mechanism for meta-learning.
Hematopoiesis and cell growth are differentially regulated by TAL1 isoforms

T-cell acute lymphoblastic leukemia (T-ALL) protein 1 (TAL1) is a central transcription factor in hematopoiesis. The timing and level of TAL1 expression orchestrate the differentiation to specialized blood cells and its overexpression is a common cause of T-ALL. Here we studied the two protein isoforms of TAL1, short and long, that are generated by the use of alternative promoters as well as by alternative splicing. We analyzed the expression of each isoform by deleting an enhancer or insulator, or by opening chromatin at the enhancer location. Our results show that each enhancer promotes expression from a specific TAL1 promoter. Expression from a specific promoter gives rise to a unique 5’ UTR with differential regulation of translation. In addition, the enhancers regulate TAL1 exon 3 alternative splicing by altering the chromatin at its location. Furthermore, our results indicate that TAL1-short binds more strongly to TAL1 E-protein partners and functions as a stronger transcription factor than TAL1-long. Specifically TAL1-short has a unique transcription signature promoting apoptosis. Finally, when we expressed both isoforms in mice bone-marrow, we found that while overexpression of both isoforms prevents lymphoid differentiation, expression of TAL-short alone leads to hematopoietic stem cell exhaustion. Furthermore, we found that TAL1-short promoted erythropoiesis and reduced cell survival in the CML cell line K562. While TAL1 and its partners are considered promising therapeutic targets in the treatment of T-ALL, our results show that TAL1-short could act as a tumor suppressor and suggest that altering TAL1 isoform’s ratio could be a preferred therapeutic approach.
Regulation of pSYSA defense plasmid copy number in Synechocystis through RNase E and a highly transcribed asRNA

Synthetic biology approaches toward the development of cyanobacterial producer strains require the availability of appropriate sets of plasmid vectors. A factor for the industrial usefulness of such strains is their robustness against pathogens, such as bacteriophages infecting cyanobacteria. Therefore, it is of great interest to understand the native plasmid replication systems and the CRISPR-Cas based defense mechanisms already present in cyanobacteria. In the model cyanobacterium Synechocystis sp. PCC 6803, four large and three smaller plasmids exist. The ∼100 kb plasmid pSYSA is specialized in defense functions by encoding all three CRISPR-Cas systems and several toxin-antitoxin systems. The expression of genes located on pSYSA depends on the plasmid copy number in the cell. The pSYSA copy number is positively correlated with the expression level of the endoribonuclease E. As molecular basis for this correlation we identified the RNase E-mediated cleavage within the pSYSA-encoded ssr7036 transcript. Together with a cis-located abundant antisense RNA (asRNA1), this mechanism resembles the control of ColE1-type plasmid replication by two overlapping RNAs, RNA I and II. In the ColE1 mechanism, two non-coding RNAs interact, supported by the small protein Rop, which is encoded separately. In contrast, in pSYSA the similar-sized protein Ssr7036 is encoded within one of the interacting RNAs and it is this mRNA that likely primes pSYSA replication. Essential for plasmid replication is furthermore the downstream encoded protein Slr7037 featuring primase and helicase domains. Deletion of slr7037 led to the integration of pSYSA into the chromosome or the other large plasmid pSYSX. Moreover, the presence of slr7037 was required for successful replication of a pSYSA-derived vector in another model cyanobacterium, Synechococcus elongatus PCC 7942. Therefore, we annotated the protein encoded by slr7037 as Cyanobacterial Rep protein A1 (CyRepA1). Our findings open new perspectives on the development of shuttle vectors for genetic engineering of cyanobacteria and of modulating the activity of the entire CRISPR-Cas apparatus in Synechocystis sp. PCC 6803.