Miracle-dz/UniFAR-FTUs huggingface dataset:
Facilitating high throughput bispecific antibody production and potential applications within biopharmaceutical discovery workflows

ABSTRACT A major driver for the recent investment surge in bispecific antibody (bsAb) platforms and products is the multitude of distinct mechanisms of action that bsAbs offer compared to a combination of two monoclonal antibodies. Four bsAb products were granted first regulatory approvals in the US or EU during 2023 and the biopharmaceutical industry pipeline is brimming with bsAb candidates across a broad range of therapeutic applications. In previously reported bsAb discovery campaigns, following a hypothesis-based choice of two specific target proteins, selections and screening activities have often been performed in mono-specific formats. The conversion to bispecific modalities has usually been positioned toward the end of the discovery process and has involved small numbers of lead molecules, largely due to challenges in expressing, purifying, and analyzing large numbers of bsAbs. In this review, we discuss emerging strategies to facilitate the production of expanded bsAb panels, focusing particularly upon combinatorial methods to generate bsAb matrices. Such technologies will enable screening in. bispecific formats at earlier stages of discovery campaigns, not only widening the accessible protein space to maximize chances of success, but also advancing empirical bi-target validation activities to assess initial target selection hypotheses.
The perception of Mandarin speech conveying communicative functions in Chinese heroin addicts

Drug addiction can cause severe damage to the human brain, leading to significant problems in cognitive processing, such as irritability, speech distortions, and exaggeration of negative stimuli. Speech plays a fundamental role in social interaction, including both the production and perception. The ability to perceive communicative functions conveyed through speech is crucial for successful interpersonal communication and the maintaining good social relationships. However, due to the limited number of previous studies, it remains unclear whether the cognitive disorder caused by drug addiction affects the perception of communicative function conveyed in Mandarin speech. To address this question, we conducted a perception experiment involving sixty male participants, including 25 heroin addicts and 35 healthy controls. The experiment aimed to examine the perception of three communicative functions (i.e., statement, interrogative, and imperative) under three background noise conditions (i.e., no noise, SNR [Signal to Noise Ratio] = 10, and SNR = 0). Eight target sentences were first recorded by two native Mandarin speakers for each of the three communicative functions. Each half was then combined with Gaussian White Noise under two background noise conditions (i.e., SNR = 10 and SNR = 0). Finally, 48 speech stimuli were included in the experiment with four options provided for perceptual judgment. The results showed that, under the three noise conditions, the average perceptual accuracies of the three communicative functions were 80.66% and 38% for the control group and the heroin addicts, respectively. Significant differences were found in the perception of the three communicative functions between the control group and the heroin addicts under the three noise conditions, except for the recognition of imperative under strong noise condition (i.e., SNR = 0). Moreover, heroin addicts showed good accuracy (around 50%) in recognizing imperative and poor accuracy (i.e., lower than the chance level) in recognizing interrogative. This paper not only fills the research gap in the perception of communicative functions in Mandarin speech among drug addicts but also enhances the understanding of the effects of drugs on speech perception and provides a foundation for the speech rehabilitation of drug addicts.
Cabergoline as a Novel Strategy for Post-Pregnancy Breast Cancer Prevention in Mice and Human

Post-pregnancy breast cancer often carries a poor prognosis, posing a major clinical challenge. The increasing trend of later-life pregnancies exacerbates this risk, highlighting the need for effective chemoprevention strategies. Current options, limited to selective estrogen receptor modulators, aromatase inhibitors, or surgical procedures, offer limited efficacy and considerable side effects. Here, we report that cabergoline, a dopaminergic agonist, reduces the risk of breast cancer post-pregnancy in a Brca1/P53-deficient mouse model, with implications for human breast cancer prevention. We show that a single dose of cabergoline administered post-pregnancy significantly delayed the onset and reduced the incidence of breast cancer in Brca1/P53-deficient mice. Histological analysis revealed a notable acceleration in post-lactational involution over the short term, characterized by increased apoptosis and altered gene expression related to ion transport. Over the long term, histological changes in the mammary gland included a reduction in the ductal component, decreased epithelial proliferation, and a lower presence of recombinant Brca1/P53 target cells, which are precursors of tumors. These changes serve as indicators of reduced breast cancer susceptibility. Additionally, RNA sequencing identified gene expression alterations associated with decreased proliferation and mammary gland branching. Our findings highlight a mechanism wherein cabergoline enhances the protective effect of pregnancy against breast cancer by potentiating postlactational involution. Notably, a retrospective cohort study in women demonstrated a markedly lower incidence of post-pregnancy breast cancer in those treated with cabergoline compared to a control group. Our work underscores the importance of enhancing postlactational involution as a strategy for breast cancer prevention, and identifies cabergoline as a promising, low-risk option in breast cancer chemoprevention. This strategy has the potential to revolutionize breast cancer prevention approaches, particularly for women at increased risk due to genetic factors or delayed childbirth, and has wider implications beyond hereditary breast cancer cases.
Tree-Ring Carbon Isotope Records from the Western Oregon Cascade Mountains Primarily Record Summer Maximum Temperatures

Abstract Here we examine climatic influences on inter-annual variation in latewood tree growth (i.e. ring-width indices, RWILW) and stable-carbon isotope discrimination (Δ13CLW) from 1950 to 2013 at two SNOTEL snowpack monitoring sites in the Oregon Cascade Mountains. Douglas-fir and mountain hemlock trees were sampled at the lower and upper elevation sites where annual peak snow water equivalent (SWE) averaged 467 and 1128 mm, respectively. RWILW chronologies were poorly correlated among sites/species (r = 0.23, P = 0.063) and neither exhibited strong correlations with monthly or seasonal climate variables. By contrast, Δ13CLW chronologies were significantly correlated (r = 0.69, P < 0.001) and exhibited stronger climate responses. Multiple regression analyses identified summertime maximum temperature (Tmax) and/or vapor pressure deficit (VPD) as the primary drivers of Δ13CLW. Secondary influences included summertime precipitation, specific humidity, cloud cover, and SWE from the previous fall and winter. Overall, our findings suggest that Cascade mixed conifer forests will become increasingly drought stressed as rising temperatures cause progressively diminished snowpacks. Moreover, our Δ13CLW records also provide a proof of concept showing strong potential to expand summertime Tmax reconstructions to other snowy, montane locations.
An evaluation of terrain‐based downscaling of fractional snow covered area data sets based on LiDAR‐derived snow data and orthoimagery

Reliable maps of snow‐covered areas at scales of meters to tens of meters, with daily temporal resolution, are essential to understanding snow heterogeneity, melt runoff, energy exchange, and ecological processes. Here we develop a parsimonious downscaling routine that can be applied to fractional snow covered area (fSCA) products from satellite platforms such as the Moderate Resolution Imaging Spectroradiometer (MODIS) that provide daily ∼500 m data, to derive higher‐resolution snow presence/absence grids. The method uses a composite index combining both the topographic position index (TPI) to represent accumulation effects and the diurnal anisotropic heat (DAH, sun exposure) index to represent ablation effects. The procedure is evaluated and calibrated using airborne‐derived high‐resolution data sets across the Tuolumne watershed, CA using 11 scenes in 2014 to downscale to 30 m resolution. The average matching F score was 0.83. We then tested our method's transferability in time and space by comparing against the Tuolumne watershed in water years 2013 and 2015, and over an entirely different site, Mt. Rainier, WA in 2009 and 2011, to assess applicability to other topographic and climatic conditions. For application to sites without validation data, we recommend equal weights for the TPI and DAH indices and close TPI neighborhoods (60 and 27 m for downscaling to 30 and 3 m, respectively), which worked well in both our study areas. The method is less effective in forested areas, which still requires site‐specific treatment. We demonstrate that the procedure can even be applied to downscale to 3 m resolution, a very fine scale relevant to alpine ecohydrology research.
Examination of social worlds of risky drinking. Insights from Twitter data analysis

Rich nature of social media data offers a great opportunity to examine social worlds of its users. Further to wide range of topics being discussed on social media, alcohol-related content is prevalent on social media and studies have found an association between this content and increased consumption of alcohol, cravings for alcohol and addiction. This study analyses social media data to examine social worlds of risky drinking in Victoria, Australia. This study conducted a scoping literature review and two online surveys, one with the general community and the other with health professionals, to determine key words to search for on social media sites. These keywords were used in a social media analytics tool called Talkwalker to generate quantitative and qualitative data on the social media users and their conversations. NVIVO was used for developing categories and themes in a sample of 172 posts. A total of 1,021 results were obtained from Twitter. The main demographic group found to be involved in conversations about drinking alcohol on Twitter was young fathers aged 25–34 years. The culture of alcohol consumption in Victoria for Twitter users is reflective of Australia’s drinking culture within which risky drinking, and in particular binge drinking, is normalised.
Baseline IgM Amounts Can Identify Patients with Poor Outcomes: Results from a Real-Life Single-Center Study on Classical Hodgkin Lymphoma

Simple Summary Hodgkin Lymphoma (HL) has a prognostic assessment often relying on PET scans after two ABVD treatment cycles (PET-2). This retrospective, observational, single–center, real-life study, evaluated 212 newly diagnosed HL patients, highlighting the role of IgM levels at diagnosis. IgM ≤ 50 mg/dL at baseline emerges as an independent predictor for progression-free survival in classic HL, offering an early and crucial prognostic marker. Additionally, the combined factors of IgM ≤ 50 mg/dL and the presence of a large nodal mass (<7 cm) serve as predictors of outcomes in classic HL, emphasizing the importance of these parameters in understanding and managing the disease above all in cases with unclear PET-2 and guaranteeing the best of care for the patients with an improved outcome. Abstract Hodgkin Lymphoma (HL) is characterized by an inflammatory background in which the reactive myeloid cells may exert an immune-suppressive effect related to the progression of the disease. Immunoglobulin M is the first antibody isotype produced during an immune response, which also plays an immunoregulatory role. Therefore, we investigated if, as a surrogate of defective B cell function, it could have any clinical impact on prognosis. In this retrospective, observational, single–center study, we evaluated 212 newly diagnosed HL patients, including 132 advanced-stage. A 50 mg/dL level of IgM at baseline resulted in 84.1% sensitivity and 45.5% specificity for predicting a complete response in the whole cohort (area under curve (AUC) = 0.62, p = 0.013). In multivariate analysis, baseline IgM ≤ 50 mg/dL and the presence of a large nodal mass (<7 cm) were independent variables able to predict the clinical outcome, while, after two cycles of treatment, IgM ≤ 50 mg/dL at baseline and PET-2 status were independent predictors of PFS. The amount of IgM at diagnosis is a valuable prognostic factor much earlier than PET-2, and it can also provide information for PET-2-negative patients. This can help to identify different HL classes at risk of treatment failure at baseline.
Effects of Probiotic-Fermented Feed on the Growth Profile, Immune Functions, and Intestinal Microbiota of Bamei Piglets

Simple Summary Fermented feed as an alternative to antibiotics in livestock is gaining interest. The purpose of this investigation was to evaluate the effects of the addition of three fermented feeds to the basal diet of Bamei piglets from the Qinghai–Tibetan Plateau. The results suggest that fermented feed has the function of improving the growth condition, immunity and intestinal flora structure of Bamei piglets. This study provides a new approach for using fermented feed as an in-feed antibiotic substitute in the raising of Bamei piglets in high-altitude environments. Abstract Purebred Bamei piglets present problems, including slow growth, respiratory disease, and post-weaning stress. This study investigated the effects of Lactobacillus plantarum QP28-1- and Bacillus subtilis QB8-fermented feed supplementation on the growth performance, immunity, and intestinal microflora of Bamei piglets from Qinghai, China. A total of 48 purebred Bamei piglets (25 days; 6.8 ± 0.97 kg) were divided into the following four groups for a 28-day diet experiment: basal feed (CK); diet containing 10% Lactobacillus plantarum-fermented feed (L); diet containing 10% Bacillus subtilis-fermented feed (B); and diet containing a mixture of 5% Lactobacillus plantarum + 5% Bacillus subtilis-fermented feed (H). The daily weight gain and daily food intake of group H increased (p < 0.05), and the feed/weight gain ratios of the groups fed with fermented feed decreased more than that of the CK group. The levels of three immune factors, namely immunoglobulin (Ig)M, IgG, and interferon-γ, were higher (p < 0.05), whereas those of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were lower (p < 0.05) in the fermented feed groups than in the CK group. Total protein was higher (p < 0.05), while urea nitrogen, total cholesterol and triglycerides were lower (p < 0.05) in the mixed-fermented feed group than in the CK group. Analysis of the gut microbiota showed that the addition of fermented feed increased the α-diversity of the gut microbiota, increasing the abundances of probiotics including Lactobacillus, Muribaculaceae, Ruminococcaceae, Prevotellaceae, and Rikenellaceae. Additionally, correlation analysis demonstrated that several of these probiotic bacteria were closely related to serum immunity. In conclusion, fermented feed supplementation rebuilt the intestinal microbiota of Bamei piglets, thereby reducing the feed/weight ratio, improving feed intake, and enhancing immunity.
Host transcriptome response to heat stress and Eimeria maxima infection in meat-type chickens

Eimeria (E.) maxima parasite infects chickens’ midgut disrupting the jejunal and ileal mucosa causing high morbidity and mortality. Heat stress (HS) is a seasonal stressor that impacts biological functions leading to poor performance. This study elucidates how HS, E. maxima infection, and their combination affect the ileum transcriptome. Two-hundred and forty 2-week-old males Ross708 chickens were randomly allocated into four treatment groups: thermoneutral-control (TNc), thermoneutral-infected (TNi), heat-stress control (HSc), and heat stress-infected (HSi), with 6 replicates each of 10 birds. Infected groups received 200x103 sporulated E. maxima oocysts/bird, and heat-treated groups were raised at 35°C. At 6-day post-treatment, ileums of five randomly selected chickens per group were sampled, RNA was extracted and sequenced. A total of 413, 3377, 1908, and 2304 DEGs were identified when applying the comparisons: TNc vs HSc, TNc vs TNi, HSi vs HSc, and TNi vs HSi, respectively, at cutoff ≥1.2-fold change (FDR: q<0.05). HSc vs TNc showed upregulation of lipid metabolic pathways and degradation/metabolism of multiple amino acids; and downregulation of most immune-related and protein synthesis pathways. TNc vs TNi displayed upregulation of most of immune-associated pathways and eukaryotic mRNA maturation pathways; and downregulation of fatty acid metabolism and multiple amino acid metabolism pathways including tryptophan. Comparing HSi versus HSc and TNi revealed that combining the two stressors restored the expression of some cellular functions, e.g., oxidative phosphorylation and protein synthesis; and downregulate immune response pathways associated with E. maxima infection. During E. maxima infection under HS the calcium signaling pathway was downregulated, including genes responsible for increasing the cytoplasmic calcium concentration; and tryptophan metabolism was upregulated, including genes that contribute to catabolizing tryptophan through serotonin and indole pathways; which might result in reducing the cytoplasmic pool of nutrients and calcium available for the parasite to scavenge and consequently might affect the parasite’s reproductive ability.
Research on joint model relation extraction method based on entity mapping

Relationship Extraction (RE) is a central task in information extraction. The use of entity mapping to address complex scenarios with overlapping triples, such as CasRel, is gaining traction, yet faces challenges such as inadequate consideration of sentence continuity, sample imbalance and data noise. This research introduces an entity mapping-based method CasRelBLCF building on CasRel. The main contributions include: A joint decoder for the head entity, utilizing Bi-LSTM and CRF, integration of the Focal Loss function to tackle sample imbalance and a reinforcement learning-based noise reduction method for handling dataset noise. Experiments on relation extraction datasets indicate the superiority of the CasRelBLCF model and the enhancement on model’s performance of the noise reduction method.
Population Subdivision and Migration Assessment of Mangalica Pig Breeds Based on Pedigree Analysis

Simple Summary The presence of substructures within isolated subpopulations can increase the risk of inbreeding. This ultimately leads to a reduction in overall genetic diversity and increased susceptibility to disease or other environmental stressors. Small subpopulations are more susceptible to genetic drift, where random events can lead to significant changes in genetic composition. This can be problematic for conservation measures aimed at preserving certain genetic traits. The Hungarian Mangalica with three different colour variants (Blonde, Red, Swallow-Bellied), representing three different breeds, have maintained their genetic and phenotypic appearance unchanged since 1976. As all breeds have been kept in multiple herds over a long period of time, the assessment of population subdivision based on these herds could help in investigating the dynamic change in population structure associated with conservation. In our study, the population substructure of each breed was evaluated using the concept of Wright-F statistics, and the results were presented using graphical methods (heat maps). The results showed that none of the breeds analysed had a composition of substructure. This favourable phenomenon is the result of an adequate migration among the herds, which proves the appropriateness of the applied breeding programme. Abstract In conserving the genetic diversity of domestic animal breeds, strategies that emphasise between-breed diversity may not be optimal, as they neglect within-breed variation. The aim of the present study was to assess the extent of population subdivision in three Mangalica pig breeds and the contribution of migration to their substructure. Wright’s FST coefficient was calculated based on genealogical data with breeding animals born between 1981 and 2023, with three colour variants (Blonde, Swallow-Belly and Red). These Wright’s FST coefficients were analysed using multidimensional scaling to reveal the population substructure. The average FST coefficient was 0.04 for the Blonde breed and 0.047 for the Swallow-Belly and Red Mangalica breeds, while these parameters were lower in the active herds at 0.03 and 0.04, respectively. The migration of individuals between herds was 61.63% for the Blonde breed and 75.53% and 63.64% for the Swallow-Belly and Red Magalica breeds, respectively. No population substructure was observed in any of the Mangalica breeds, which can be explained by the extensive migration between herds.
The Lessac Technologies System for Blizzard Challenge 2011

Lessac Technologies has developed a technology for concatenative speech synthesis based on a novel approach for describing speech in which expressivity, voice quality, and speaking style are fundamental. The main aspect of our system is that instead of traditional phonetic symbols, we use a much more fine-grained and richer set of entities called Lessemes to describe speech and to label units, which allow a richer and more precise characterization of speech sounds. The front-end part of our synthesizer translates plain input text into a sequence of these units by syntactic parsing and applying a set of rules developed from expertise. We use a Bayesian method to obtain a particular trainable mapping from linguistic and prosodic features encoded in the Lessemes to a trajectory in the acoustic parameter space. Unit selection consists of selecting the best candidate units from a data base to match them to the target trajectory, while minimizing discontinuities between them.
The effect of moderate and vigorous aerobic exercise training on the cognitive and walking ability among stroke patients during different periods: A systematic review and meta-analysis

Objective The study examined whether rehabilitation using aerobic exercise is more appropriate for patients less than 3 months post-stroke or more appropriate for patients more than 3 months post-stroke. Method PubMed, Embase, Web of Science, Scopus and CNKI databases were searched from inception to September 2023. All studies included must be written in English and grey literature was excluded. The quality of the study was evaluated using the PEDro scale. Standard mean difference (SMD) and 95% confidence interval (CI) were calculated. The primary outcomes are cognitive ability and walking ability. The intervention of the experimental group must be or include high-intensity aerobic training or moderate-intensity aerobic training. In addition, we required low intensity routine exercises in control group. Result Only 15 studies were included in this meta-analysis. The results showed that aerobic exercise has a positive rehabilitation effect on cognitive and walking ability of stroke patients. Global Cognitive Function (SMD = 0.81 95%CI 0.49–1.12), Walking Capacity (SMD = 1.19, 95%CI 0.75–1.62), VO2peak (SMD = 0.97, 95%CI 0.66–1.28), and brain-derived neurotrophic factor (SMD = 2.73, 95%CI 2.03–3.43). We further observed that patients who suffered a stroke within the past three months exhibited superior rehabilitation outcomes compared to patients who suffered a stroke more than three months ago, specifically in terms of cognitive ability, walking tests, and cardiopulmonary function. Conclusions It is recommended to carry out treatment for patients in the initial stage of stroke, and it is required to pay attention to exercise intensity in the process of treatment to ensure patient safety.