Miracle-dz/UniFAR-FTUs huggingface dataset:
HPV Sequencing Facilitates Ultrasensitive Detection of HPV Circulating Tumor DNA

Purpose: Human papillomavirus (HPV) DNA offers a convenient circulating tumor DNA (ctDNA) marker for HPV-associated malignancies, but current methods, such as digital PCR (dPCR), provide insufficient accuracy for clinical applications in patients with low disease burden. We asked whether a next-generation sequencing approach, HPV sequencing (HPV-seq), could provide quantitative and qualitative assessment of HPV ctDNA in low disease burden settings. Experimental Design: We conducted preclinical technical validation studies on HPV-seq and applied it retrospectively to a prospective multicenter cohort of patients with locally advanced cervix cancer (NCT02388698) and a cohort of patients with oropharynx cancer. HPV-seq results were compared with dPCR. The primary outcome was progression-free survival (PFS) according to end-of-treatment HPV ctDNA detectability. Results: HPV-seq achieved reproducible detection of HPV DNA at levels less than 0.6 copies in cell line data. HPV-seq and dPCR results for patients were highly correlated (R2 = 0.95, P = 1.9 × 10–29) with HPV-seq detecting ctDNA at levels down to 0.03 copies/mL plasma in dPCR-negative posttreatment samples. Detectable HPV ctDNA at end-of-treatment was associated with inferior PFS with 100% sensitivity and 67% specificity for recurrence. Accurate HPV genotyping was successful from 100% of pretreatment samples. HPV ctDNA fragment sizes were consistently shorter than non–cancer-derived cell-free DNA (cfDNA) fragments, and stereotyped cfDNA fragmentomic patterns were observed across HPV genomes. Conclusions: HPV-seq is a quantitative method for ctDNA detection that outperforms dPCR and reveals qualitative information about ctDNA. Our findings in this proof-of-principle study could have implications for treatment monitoring of disease burden in HPV-related cancers. Future prospective studies are needed to confirm that patients with undetectable HPV ctDNA following chemoradiotherapy have exceptionally high cure rates.
Effect of Phase Change Material Cooling Vests on Body Thermoregulation and Thermal Comfort of Patients With Paraplegia: A Human Subject Experimental Study

Study design Randomized experimental study. Objective Compared to able-bodied people, patients with paraplegia due to thoracic spinal cord injury (SCI) are at an increased risk of heat illnesses during exercise due to impaired thermoregulatory responses. To overcome this limitation, we investigated the performance of three phase change material (PCM) cooling vests of different melting temperatures (Eijsvogels, #49) and coverage area of the trunk. Methods Sixteen participants were divided into three groups according to their injury level. All were tested for V20 full vest (20°C Tm, 75% coverage). Mid-thoracic and high-thoracic groups were tested for V14 vest (14°C Tm, 75% coverage). The mid-thoracic group was tested for V20 half vest (20°C Tm, 50% coverage). The participants performed a 30-min arm-crank exercise followed by a recovery period inside a controlled hot climatic chamber. The heart rate, segmental skin (Tskin), and core temperature (Tcore) values were recorded, and subjective questionnaires were taken. Results Compared to no vest (NV) test, all the vests showed an effective decrease in Tskin values of the trunk. However, the decrease in Tskin was not enough to induce a significant decrease in Tcore in all three groups. Mid-thoracic and low-thoracic groups showed a reduction in the increasing Tcore by the end of the exercise and recovery period. Finally, the level of thermal comfort was enhanced for the three groups. Conclusion The effectiveness of cooling vests for persons with paraplegia is dependent on injury level and thus the ratio of sensate to insensate skin. Future studies necessitate the investigation of the cooling effects of PCM vests at a lower Tm with a larger sample size.
Successful PD-1 inhibitor treatment in a patient with refractory transformed follicular lymphoma who failed to respond to CAR-T cell therapy: a case report and literature review

ABSTRACT Follicular lymphoma (FL) accounts for approximately 35% of all non-Hodgkin lymphomas and can progress to diffuse large B cell lymphoma (DLBCL) at a rate of 2% per year. Here, we present a 56-year-old female patient who was diagnosed with grade 3a FL. Further pathological investigation revealed that the lymphoma had transformed into DLBCL following six courses of R-CHOP regimen, and further disease progression was observed after two courses of R2-GemOx. We ultimately failed to collect hematopoietic stem cells after two courses of R2-ICE. CD-22 CAR-T cell therapy salvaged the patient; however, a new soft tissue mass of 4.8 × 4.1 cm rapidly emerged in the patient’s right lung. Following the observation of strong tissue staining of PD-L1 (90%), the patient was administered PD-1 inhibitor and 26 Gy of radiotherapy and has maintained progression-free survival at more than 15 months of follow-up. Transformed FL with strong PD-L1 expression showed a poor response to standard immunochemotherapy. Our findings support the potential benefit of PD-1 inhibitor and combination therapies in this type of transformed FL.
A Quantitative Analysis of Cell Bridging Kinetics on a Scaffold Using Computer Vision Algorithms

Tissue engineering involves the seeding of cells into a structural scaffolding to regenerate the architecture of damaged or diseased tissue. To effectively design a scaffold, an understanding of how cells collectively sense and react to the geometry of their local environment is needed. Advances in the development of melt electro-writing have allowed micron and submicron polymeric fibres to be accurately printed into porous, complex and three-dimensional structures. By using melt electrowriting, we created a geometrically relevant in vitro scaffold model to study cellular spatial-temporal kinetics. These scaffolds were paired with custom computer vision algorithms to investigate cell nuclei, cell membrane actin and scaffold fibres over different pore sizes (200-600 µm) and time points (28 days). We find that cells proliferated much faster in the smaller (200 µm) pores which halved the time until confluence versus larger (500 and 600 µm) pores. Our analysis of stained actin fibres revealed that cells were highly aligned to the fibres and the leading edge of the pore filling front, and we found that cells behind the leading edge were not aligned in any particular direction. This study provides a systematic understanding of cellular spatial temporal kinetics within a 3D in vitro model to inform the design of more effective synthetic tissue engineering scaffolds for tissue regeneration. STATEMENT OF SIGNIFICANCE: : Advances in the development of melt electro-writing have allowed micron and submicron polymeric fibres to be accurately printed into porous, complex and three-dimensional structures. By using melt electrowriting, we created a geometrically relevant in vitro model to study cellular spatial-temporal kinetics to provide a systematic understanding of cellular spatial temporal kinetics within a 3D in vitro model. The insights presented in this work help to inform the design of more effective synthetic tissue engineering scaffolds by reducing cell culture time; which is valuable information for the implant or lab-grown-meat industries.
Effect of crank length on biomechanical parameters and muscle activity during standing cycling

ABSTRACT This study investigated the effect of crank length on biomechanical parameters and muscle activity during standing cycling. Ten participants performed submaximal cycling trials on a stand-up bicycle using four crank lengths. Joint angles, moments, powers, and works of the lower limbs were calculated from motion data and pedal reaction forces. Electromyographic (EMG) data were recorded from gluteus maximus (GM), vastus medialis, rectus femoris, biceps femoris (BF), gastrocnemius medialis, soleus, and tibialis anterior, and used to obtain the integrated EMG. Statistical parametric mapping was employed to analyse the biomechanical parameters throughout the pedalling cycle. Knee and hip flexion angles and hip power increased at the initiation (0–20%) of pedalling with increasing crank length, while the BF and GM muscle activities increased during propulsion (20–40%). Additionally, increasing the crank length resulted in increased knee power absorption during upstroke phase (70–100%). Peak knee extension moment increased with decreasing crank length during propulsion, but the moment at a short crank length during propulsion was comparable to fast walking. Consequently, longer crank lengths require increased propulsion power by the lower limb muscles during standing cycling compared to shorter crank lengths. Therefore, shorter crank lengths are recommended for stand-up bicycles to avoid fatigue.
The wear behavior of Al/(Al2O3 + SiC + C) hybrid composites fabricated stir casting assisted squeeze

ABSTRACT Economically fabrication and achieving appropriate properties of HMMCs is a challenge. Keeping in view, an oil fired muffle furnace has been designed and developed for melting of Al matrix. Hybrid Al/(Al2O3 + SiC + C)MMCs were fabricated by liquid stir with squeeze casting. In addition, an electrochemical micro-machining (ECMM) setup has been developed and utilized for micro-machining of hybrid MMC. The wear tests were carried out on a pin on disc machine at a constant track diameter of 60 mm, by varying speed of disc at 300, 600, and 1200 rpm and applying the varying loads at 4.91, 9.82, and 14.72 N under dry sliding conditions. The HMMC with 20% SiC, 7.5% C, and 10% Al2O3 was found to be the best wear resistance under high load and high speed. The wear resistance was improved by 64.28 and 85.29%, when carbon particles reinforcement content increased from 3 to 5% and 3 to 7.5%, respectively. The machined surface texture and decomposition of metallic compounds deposited on workpiece were measured and analyzed through various SEM, EDX, and XRD images.
Estimating HLA haplotype frequencies from homozygous individuals – A Technical Report

We estimated HLA haplotype frequencies based on individuals homozygous for 4, 5 or 6 loci. Validation of our approach using a sample of over 3.4 million German individuals was successful. Compared to an expectation‐maximization algorithm, the errors were larger. However, our approach allows the unequivocal detection of rare haplotypes.
Cosmopolitan morality trades off in-group for the world, separating benefits and protection

Significance Contemporary world challenges—pandemic response, climate change, migration, global poverty, and trade policy—require comparative moral judgments (tradeoffs) between one’s own and other nations. Such choices distribute benefits and protect security for just the national in-group or the whole world. In representative surveys from eight countries, most respondents are willing to sacrifice national well-being to aid foreigners, more to protect from harms than to redistribute benefits. This disaggregates two dimensions of moral cosmopolitanism (benefiting versus protecting), distinguishes it from adjacent constructs (such as group identity), and demonstrates links to attitudes and behaviors. Cognitive associations (global, inclusive words) reflect cosmopolitan thinking; making the world salient can elicit cosmopolitan behavior, at least temporarily. Understanding this global perspective can guide its enhancement. Global cooperation rests on popular endorsement of cosmopolitan values—putting all humanity equal to or ahead of conationals. Despite being comparative judgments that may trade off, even sacrifice, the in-group’s interests for the rest of the world, moral cosmopolitanism finds support in large, nationally representative surveys from Spain, the United Kingdom, Germany, China, Japan, the United States, Colombia, and Guatemala. A series of studies probe this trading off of the in-group’s interests against the world’s interests. Respondents everywhere distinguish preventing harm to foreign citizens, which almost all support, from redistributing resources, which only about half support. These two dimensions of moral cosmopolitanism, equitable security (preventing harm) and equitable benefits (redistributing resources), predict attitudes toward contested international policies, actual charitable donations, and preferences for mask and vaccine allocations in the COVID-19 response. The dimensions do not reflect several demographic variables and only weakly reflect political ideology. Moral cosmopolitanism also differs from related psychological constructs such as group identity. Finally, to understand the underlying thought structures, natural language processing reveals cognitive associations underlying moral cosmopolitanism (e.g., world, both) versus the alternative, parochial moral mindset (e.g., USA, first). Making these global or local terms accessible introduces an effective intervention that at least temporarily leads more people to behave like moral cosmopolitans.
Could computed tomography histogram analysis add value to the diagnosis of cholesteatoma?

Background/aim To investigate the potential role of computed tomography (CT) histogram analysis in differentiating cholesteatoma (CHS) and non-cholesteatoma (NCHS). Materials and methods We evaluated 77 temporal bone CT images (from November 2016 to February 2020) that were obtained pre-operatively (mean age, 37.10±17.27 years in CHS; 36.72±16.08 years in NCHS group). Histogram analyses of the resulting XML files were conducted using the R Project 3.3. 2 program. ROC analysis was used to find threshold values, and the diagnostic efficiency of these values in differentiating CHS-NCHS was determined. Results The CT images of 41 CHS (53.25%) and 36 NHCS cases (46.75%) were evaluated. There was a statistically significant difference between the CHS and NCHS group in terms of the mean, maximum, and median values (p = 0.036, p = 0.006, p = 0.043). When examining the ROC curve obtained from the mean of these parameters, area under the curve (AUC) is determined as 0.638, and when the threshold value is selected as 42.55, the mean value was determined to have a sensitivity of 86.50% and specificity of 56.10% in differentiating CHS-NCHS. Conclusion In cases with magnetic resonance imaging (MRI) contraindications, small-sized lesions may be difficult to detect and characterize due to a poor resolution; to reduce the rate of false positives/negatives in these situations, CT histogram analysis of previously taken images may provide the additional information.
Periorbital aesthetic concerns in patients seeking corneal refractive surgery

Purpose: To report the frequency of periorbital aesthetic abnormalities in patients undergoing refractive surgery and to report the ability of the patient and the refractive surgeon in picking up these findings compared to the oculoplastic surgeon. Methods: Single-center, prospective observational case series. All patients underwent standard pre-operative work-up for refractive surgery, answered a study questionnaire, and underwent face photographs (with and without glasses). The patient, the refractive, and the oculoplastic surgeons evaluated the photographs to categorize the concerns as none, presence of ptosis, tear trough deformity, scleral show, and others. The findings of the oculoplastic surgeon were taken as the standard of reference. Results: The photographs of 121 patients were analyzed. The mean age was 25.76 ± 3.75 years and 72% were males. The main indication for surgery was to eliminate dependency on glasses in a majority (76%) followed by cosmesis in 23%. The oculoplastic surgeon noted tear trough deformity in 14 (11.5%) cases, scleral show in 51 (42.1%), ptosis in 35 (28.9%), and other findings in 45 (37.1%). When the symmetrical scleral show was excluded, the patient picked up aesthetic concerns in only 8.26%, the refractive surgeon in 14% as compared to 39% by the oculoplastic surgeon (P < 0.01). Conclusion: Periorbital aesthetic significant findings were noted in 39% of the patients undergoing corneal refractive surgery when assessed by an oculoplastic surgeon. The refractive surgeon was able to pick up less than 50% of these. We recommend a basic aesthetic initial evaluation prior to refractive surgery and photographic documentation, especially in cosmetically aware patients.
Midbrain dopaminergic innervation of the hippocampus is sufficient to modulate formation of aversive memories

Significance The origin and mode of action of dopamine on hippocampus-dependent memory have been a matter of interest for many years. The latest research has pointed toward the locus coeruleus as the main source of hippocampal dopamine, while inputs from midbrain dopaminergic centers remain controversial and understudied. We provide anatomical evidence for a direct dopaminergic projection to the hippocampus from a distinct, identified midbrain population and report a bidirectional modulation of hippocampal-aversive learning by midbrain dopamine. Our data indicate that this modulation is sustained even in the absence of catecholamine release from the locus coeruleus. These results demonstrate that midbrain dopaminergic innervation of the dorsal hippocampus is significant and plays a functional role in the modulation of aversive memory formation. Aversive memories are important for survival, and dopaminergic signaling in the hippocampus has been implicated in aversive learning. However, the source and mode of action of hippocampal dopamine remain controversial. Here, we utilize anterograde and retrograde viral tracing methods to label midbrain dopaminergic projections to the dorsal hippocampus. We identify a population of midbrain dopaminergic neurons near the border of the substantia nigra pars compacta and the lateral ventral tegmental area that sends direct projections to the dorsal hippocampus. Using optogenetic manipulations and mutant mice to control dopamine transmission in the hippocampus, we show that midbrain dopamine potently modulates aversive memory formation during encoding of contextual fear. Moreover, we demonstrate that dopaminergic transmission in the dorsal CA1 is required for the acquisition of contextual fear memories, and that this acquisition is sustained in the absence of catecholamine release from noradrenergic terminals. Our findings identify a cluster of midbrain dopamine neurons that innervate the hippocampus and show that the midbrain dopamine neuromodulation in the dorsal hippocampus is sufficient to maintain aversive memory formation.
RiboRid: A low cost, advanced, and ultra-efficient method to remove ribosomal RNA for bacterial transcriptomics

RNA sequencing techniques have enabled the systematic elucidation of gene expression (RNA-Seq), transcription start sites (differential RNA-Seq), transcript 3′ ends (Term-Seq), and post-transcriptional processes (ribosome profiling). The main challenge of transcriptomic studies is to remove ribosomal RNAs (rRNAs), which comprise more than 90% of the total RNA in a cell. Here, we report a low-cost and robust bacterial rRNA depletion method, RiboRid, based on the enzymatic degradation of rRNA by thermostable RNase H. This method implemented experimental considerations to minimize nonspecific degradation of mRNA and is capable of depleting pre-rRNAs that often comprise a large portion of RNA, even after rRNA depletion. We demonstrated the highly efficient removal of rRNA up to a removal efficiency of 99.99% for various transcriptome studies, including RNA-Seq, Term-Seq, and ribosome profiling, with a cost of approximately $10 per sample. This method is expected to be a robust method for large-scale high-throughput bacterial transcriptomic studies.
Trajectories of attitude toward own aging and subjective age from 2008 to 2020 among middle-aged and older adults: Partial evidence of a "COVID-19 effect".

As older adults have frequently been portrayed as one homogeneous and vulnerable risk group in public debates and in the media immediately after the outbreak of the Coronavirus disease (COVID-19) pandemic, a general shift toward less favorable attitude toward own aging (ATOA) might have resulted. In contrast, individuals may feel younger than before the pandemic, reflecting a psychological mechanism to avoid identifying themselves with the old age "risk group. " We investigate 12-year trajectories of ATOA and subjective age among middle-aged and older German adults based on assessments between 2008 and Summer 2020 (N = 7,730; age in 2008: 40-93 years, M = 62.41). Based on longitudinal multilevel regression models, we found that for ATOA, a model including a potentially "pandemic-driven" change component between 2017 and 2020 in addition to an overall linear change between 2008 and 2020 revealed a better fit than a linear change model without that additional change component. Mean-level decline in ATOA between 2017 and 2020 was five times steeper in such a model than in a linear change model that did not include an additional 2017-2020 change component. The extent of intraindividual ATOA change between 2017 and 2020 varied interindividually, but for more than 99% of the sample, particularly among those with poorer self-rated health, ATOA became less favorable. There was very limited evidence for a pandemic-specific change in subjective age. In conclusion, our findings suggest that the early phase of the pandemic might have caused a change toward less favorable ATOA, whereas it did not affect subjective age. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Sex and Age Differences in Activity Budgets in a Population of Captive African Penguins (Spheniscus demersus)

ABSTRACT The African penguin (Spheniscus demersus) is an endangered species that continues to experience population decline. Understanding the behavior of this species is a critical step in the conservation efforts to prevent their extinction. A comprehensive activity budget of this species has yet to be conducted in any captive population, which are critical for the Species Survival Plan (SSP) breeding programs. We performed scan sampling observations on a group of 19 penguins to construct an activity budget. We also investigated the behavioral differences between males and females, as well as between adults and juveniles. Results indicate there are minimal sex differences in time budget allocations, but there are some notable age related differences. Creating and comparing activity budgets between populations are critical for understanding animal welfare in captive settings.