Miracle-dz/UniFAR-FTUs huggingface dataset:
Establishment of a pure culture of immature Sertoli cells by PDGFRA staining and cell sorting

Sertoli cells are key somatic cells in the testis that form seminiferous tubules and support spermatogenesis. The isolation of pure Sertoli cells is important for their study. However, it is a difficult effort because of the close association of Sertoli cells with peritubular myoid cells surrounding seminiferous tubules. Here, we propose a novel approach to the establishment of a pure Sertoli cell culture from immature mouse testes. It is based on the staining of testicular cells for platelet‐derived growth factor receptor alpha (PDGFRA), followed by fluorescence‐activated cell sorting and culturing of a PDGFRA‐negative cell population. Cells positive for a Sertoli cell marker WT1 accounted for more than 96% of cells in cultures from 6 to 12 days postpartum (dpp) mice. The numbers of peritubular myoid cells identified by ACTA2 staining did not exceed 4%. Cells in the cultures were also positive for Sertoli cell proteins SOX9 and DMRT1. Amh and Hsd17b3 expression decreased and Ar and Gata1 expression increased in 12 dpp cultures compared to 6 dpp cultures, which suggests that cultured Sertoli cells at least partially retained their differentiation status. This method can be employed in various applications including the analysis of differential gene expression and functional studies.
Semitendinosus vs Gracilis Grafts With 1- vs 2-Tunnel Techniques for Coracoclavicular Ligament Reconstruction: A Biomechanical Study

Background: Despite the evolution of acromioclavicular joint surgery to a more anatomic coracoclavicular (CC) ligament reconstruction, no definitive guidance regarding the number and position of bone tunnels in the clavicle, as well as the ideal graft choice, is established. Purpose/Hypothesis: The purpose of this study was to biomechanically compare the reconstruction of the CC ligament complex between gracilis- and semitendinosus-tendon grafts in 1- and 2-tunnel techniques. It was hypothesized that the gracilis tendon graft will provide comparable primary stability in both tunnel techniques while utilizing a smaller tunnel diameter. Study Design: Controlled laboratory study. Methods: A total of 24 cadaveric shoulders (13 men, 11 women; 66 ± 7.5 years) were randomly allocated to 4 repair groups: gracilis with 1 tunnel (GT-1), gracilis with 2 tunnels (GT-2), semitendinosus with 1 tunnel (ST-1), and semitendinosus with 2 tunnels (ST-2). First, specimens were tested for native anterior, posterior, and superior translations. Then, specimens were randomly assigned to 1 of the 4 CC reconstruction groups before undergoing the same testing, followed by cyclic loading and load to failure (LTF). Results: The GT-2 reconstruction demonstrated significantly less translation when compared with ST-2 in anterior (P = .024) and posterior (P = .048) directions. GT-1 and ST-2 both showed significantly less translation than ST-1 in anterior and superior directions (P < .001). All reconstructions demonstrated less superior translation compared with native testing, with GT-1 and ST-2 significantly less than ST-1 (P < .001). There were no significant differences for peak displacement and LTF between groups. Conclusion: Gracilis tendon grafts using a 1- or 2-tunnel technique for CC ligament reconstruction provided comparable translation, displacement, and LTF as corresponding semitendinosus grafts. Therefore, the gracilis tendon should be considered as a biomechanical equivalent graft choice for the reconstruction of the CC ligament complex. Clinical Relevance: In a cadaveric model, the gracilis tendon demonstrated adequate fixation with minimal translation in CC ligament reconstruction while utilizing smaller diameter bone tunnels, which may help minimize the risk of complications such as loss of reduction and fracture.
Caffeic acid dimethyl ether alleviates alcohol-induced hepatic steatosis via microRNA-378b-mediated CaMKK2-AMPK pathway

ABSTRACT Alcoholic liver disease (ALD), with its increasing morbidity and mortality, has seriously and extensively affected the health of people worldwide. Caffeic Acid Dimethyl Ether (CADE) significantly inhibits alcohol-induced hepatic steatosis in vivo through AMP-activated protein kinase (AMPK) pathway, but its in-depth mechanism remains unclear. This work aimed to clarify further mechanism of CADE in improving hepatic lipid accumulation in ALD through the microRNA-378b (miR-378b)-mediated Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2)-AMPK signaling pathway. Here, we reported that the hepatic or serum triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), and aspartate transaminase (AST) levels were sharply escalated by ethanol while prominently decreased by CADE. Ethanol sharply up-regulated miR-378b expression while CADE effectively prevented the elevation of miR-378b in vivo. And treatment of CADE surely increased mRNA and protein expression of CaMKK2 as a kinase of AMPK and reduced lipid accumulation in the livers of alcohol-fed C57BL/6 mice. MiR-378b escalation exacerbated hepatic steatosis and inhibited CaMKK2-AMPK signaling, while miR-378b deficiency alleviated lipid accumulation and activated the CaMKK2 cascade. Furthermore, CADE alleviated the lipid deposition and reversed the disorder of CaMKK2-AMPK signaling pathway induced by miR-378b over-expression. However, knockdown of miR-378b eliminated the beneficial effect of CADE on lipid metabolism. In brief, our results showed that CADE ultimately improved hepatic lipid deposition by regulating the CaMKK2-AMPK signaling pathway through miR-378b. Graphical abstract
Prefusion F Protein-Based Respiratory Syncytial Virus Immunization in Pregnancy.

BACKGROUND Respiratory syncytial virus (RSV), a major cause of illness and death in infants worldwide, could be prevented by vaccination during pregnancy. The efficacy, immunogenicity, and safety of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine in pregnant women and their infants are uncertain. METHODS In a phase 2b trial, we randomly assigned pregnant women, at 24 through 36 weeks' gestation, to receive either 120 or 240 μg of RSVpreF vaccine (with or without aluminum hydroxide) or placebo. The trial included safety end points and immunogenicity end points that, in this interim analysis, included 50% titers of RSV A, B, and combined A/B neutralizing antibodies in maternal serum at delivery and in umbilical-cord blood, as well as maternal-to-infant transplacental transfer ratios. RESULTS This planned interim analysis included 406 women and 403 infants; 327 women (80.5%) received RSVpreF vaccine. Most postvaccination reactions were mild to moderate; the incidence of local reactions was higher among women who received RSVpreF vaccine containing aluminum hydroxide than among those who received RSVpreF vaccine without aluminum hydroxide. The incidences of adverse events in the women and infants were similar in the vaccine and placebo groups; the type and frequency of these events were consistent with the background incidences among pregnant women and infants. The geometric mean ratios of 50% neutralizing titers between the infants of vaccine recipients and those of placebo recipients ranged from 9.7 to 11.7 among those with RSV A neutralizing antibodies and from 13.6 to 16.8 among those with RSV B neutralizing antibodies. Transplacental neutralizing antibody transfer ratios ranged from 1.41 to 2.10 and were higher with nonaluminum formulations than with aluminum formulations. Across the range of assessed gestational ages, infants of women who were immunized had similar titers in umbilical-cord blood and similar transplacental transfer ratios. CONCLUSIONS RSVpreF vaccine elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns. (Funded by Pfizer; ClinicalTrials.gov number, NCT04032093.).
Neural Mechanisms of Facial Emotion Recognition in Autism: Distinct Roles for Anterior Cingulate and dlPFC

ABSTRACT Objective The present study sought to measure and internally validate neural markers of facial emotion recognition (FER) in adolescents and young adults with ASD to inform targeted intervention. Method We utilized fMRI to measure patterns of brain activity among individuals with ASD (N = 21) and matched controls (CON; N = 20) 2 s prior to judgments about the identity of six distinct facial emotions (happy, sad, angry, surprised, fearful, disgust). Results Predictive modeling of fMRI data (support vector classification; SVC) identified mechanistic roles for brain regions that forecasted correct and incorrect identification of facial emotion as well as sources of errors over these decisions. BOLD signal activation in bilateral insula, anterior cingulate (ACC) and right dorsolateral prefrontal cortex (dlPFC) preceded accurate FER in both controls and ASD. Predictive modeling utilizing SVC confirmed the utility of ACC in forecasting correct decisions in controls but not ASD, and further indicated that a region within the right dlPFC was the source of a type 1 error signal in ASD (i.e. neural marker reflecting an impending correct judgment followed by an incorrect behavioral response) approximately two seconds prior to emotion judgments during fMRI. Conclusions ACC forecasted correct decisions only among control participants. Right dlPFC was the source of a false-positive signal immediately prior to an error about the nature of a facial emotion in adolescents and young adults with ASD, potentially consistent with prior work indicating that dlPFC may play a role in attention to and regulation of emotional experience.
Using Smartphone Sensor Paradata and Personalized Machine Learning Models to Infer Participants’ Well-being: Ecological Momentary Assessment

Background Sensors embedded in smartphones allow for the passive momentary quantification of people’s states in the context of their daily lives in real time. Such data could be useful for alleviating the burden of ecological momentary assessments and increasing utility in clinical assessments. Despite existing research on using passive sensor data to assess participants’ moment-to-moment states and activity levels, only limited research has investigated temporally linking sensor assessment and self-reported assessment to further integrate the 2 methodologies. Objective We investigated whether sparse movement-related sensor data can be used to train machine learning models that are able to infer states of individuals’ work-related rumination, fatigue, mood, arousal, life engagement, and sleep quality. Sensor data were only collected while the participants filled out the questionnaires on their smartphones. Methods We trained personalized machine learning models on data from employees (N=158) who participated in a 3-week ecological momentary assessment study. Results The results suggested that passive smartphone sensor data paired with personalized machine learning models can be used to infer individuals’ self-reported states at later measurement occasions. The mean R2 was approximately 0.31 (SD 0.29), and more than half of the participants (119/158, 75.3%) had an R2 of ≥0.18. Accuracy was only slightly attenuated compared with earlier studies and ranged from 38.41% to 51.38%. Conclusions Personalized machine learning models and temporally linked passive sensing data have the capability to infer a sizable proportion of variance in individuals’ daily self-reported states. Further research is needed to investigate factors that affect the accuracy and reliability of the inference.
Gene‐environment interaction in type 2 diabetes in Korean cohorts: Interaction of a type 2 diabetes polygenic risk score with triglyceride and cholesterol on fasting glucose levels

Type 2 diabetes (T2D) is caused by genetic and environmental factors as well as gene‐environment interactions. However, these interactions have not been systematically investigated. We analyzed these interactions for T2D and fasting glucose levels in three Korean cohorts, HEXA, KARE, and CAVAS, using the baseline data with a multiple regression model. Two polygenic risk scores for T2D (PRST2D) and fasting glucose (PRSFG) were calculated using 488 and 82 single nucleotide polymorphisms (SNP) for T2D and fasting glucose, respectively, which were extracted from large‐scaled genome‐wide association studies with multiethnic data. Both lifestyle risk factors and T2D‐related biochemical measurements were assessed. The effect of interactions between PRST2D‐triglyceride (TG) and PRST2D‐total cholesterol (TC) on fasting glucose levels was observed as follows: β ± SE = 0.0005 ± 0.0001, p = 1.06 × 10−19 in HEXA, β ± SE = 0.0008 ± 0.0001, p = 2.08 × 10−8 in KARE for TG; β ± SE = 0.0006 ± 0.0001, p = 2.00 × 10−6 in HEXA, β ± SE = 0.0020 ± 0.0004, p = 2.11 × 10−6 in KARE, β ± SE = 0.0007 ± 0.0004, p = 0.045 in CAVAS for TC. PRST2D‐based classification of the participants into four groups showed that the fasting glucose levels in groups with higher PRST2D were more adversely affected by both the TG and TC. In conclusion, blood TG and TC levels may affect the fasting glucose level through interaction with T2D genetic factors, suggesting the importance of consideration of gene‐environment interaction in the preventive medicine of T2D.
Research Using Social Media to Recruit Research Participants Should Proceed With Caution. Comment on “Telemanagement of Home-Isolated COVID-19 Patients Using Oxygen Therapy With Noninvasive Positive Pressure Ventilation and Physical Therapy Techniques: Randomized Clinical Trial”

UNSTRUCTURED The original article provided a deeper understanding on the effectiveness of home-based oxygen therapy with bilevel positive airway pressure and that of osteopathic manipulative respiratory and physical therapy techniques in impeding exacerbation of early-stage COVID-19 pneumonia. In this letter, we propose further issues that should be discussed in terms of research design, technologies for patient recruitment, and the influence of a telemanagement system on health care development.
An introductory review of robotically assisted surgical systems

The scope of the work is to present the state of the art of robotically assisted surgical systems and to give a general idea about how technology can help today and tomorrow robotic surgery. The road to innovation passes through research and on field trials; for this reason, not only commercial surgery robots, but also innovative prototype robots, proposed by the Academic world, are presented.
Does Varying Resistance Exercises for the Same Muscle Group Promote Greater Strength Gains?

Abstract Costa, BDV, Kassiano, W, Nunes, JP, Kunevaliki, G, Castro-E-Souza, P, Sugihara-Junior, P, Fernandes, RR, Cyrino, ES, and de Fortes, LS. Does varying resistance exercises for the same muscle group promote greater strength gains? J Strength Cond Res 36(11): 3032–3039, 2022—Two of the foremost principles of progression are progressive overload and variation. A way to vary within a resistance training (RT) program is to perform different exercises for the same muscle group; however, this strategy is still overlooked. The purpose of the present study was to compare strength adaptations between an RT routine that maintained the exercises fixed (N-VAR) and another that varied the exercises for the same muscle group during the weekly sessions (VAR). Twenty-three young men (23.3 ± 4.1 years) were randomly allocated to N-VAR (n = 11) and VAR (n = 12) conditions. The RT was performed 3 times a week for 9 weeks and consisted of a whole-body routine (3 sets of 8–12 repetitions). Maximum dynamic strength was assessed using the 1-repetition maximum test (1RM), and the isometric strength was assessed using an isokinetic dynamometer, before and after training. Following the training period, both groups increased the 1RM values in all exercises (p ≤ 0.002), without significant differences between them (p ≥ 0.20). In contrast, a greater increase (p = 0.02) in isometric knee extension strength was showed to N-VAR (+12%) compared with VAR (+7%). There was no significant increase in both groups for isometric knee flexion strength (N-VAR, p = 0.10; VAR, p = 0.18). Our findings indicate that maintaining or varying the exercises for the same muscle group promotes similar adaptations in the maximum dynamic strength. In contrast, for the isometric strength in knee extension, maintaining the fixed exercises seems to be more interesting.
Overview of basic epidemiological characteristics and descriptive analysis of the incidence of human yersiniosis in the Czech Republic in 2018-2020.

OBJECTIVE The aim was to provide an overview of the basic epidemiological characteristics of human yersiniosis and to analyze the reported epidemiological data on the incidence of this disease in the Czech Republic (CZ) in 2018-2020. METHODS A descriptive analysis was performed of cases of yersiniosis captured in the Infectious Disease Information System (ISIN) in the CZ in 2018-2020. MS Excel 2010 was used for data processing and sorting. RESULTS In the CZ, a total of 1,686 cases of yersiniosis were reported in 2018-2020 (average annual incidence of 5/100,000 population). The highest average age-specific incidence was recorded in the age group 1-4 years (31.3/100,000), followed by 0-year-olds (26.9/100,000). In the study period, 942 cases were male and 744 cases were female, with the respective incidences of 6.0 /100,000 and 4.6/100,000. By administrative region, the highest average annual incidences were recorded in the South Moravian (9.1/100,000) and Moravian-Silesian (7.5/100,000) Regions. Hospital admission was required for 14.3% (n = 241) of reported cases. No death or outbreak was reported during the study period. A total of 31 cases were imported from usual recreational destinations. No seasonality was detected in the CZ; however, more cases always occur in January and in the second half of the year. Over the last three years, a stagnant trend in the incidence of the disease has been observed in the CZ. CONCLUSIONS In 2018 and 2019, yersiniosis (caused by Y. enterocolitica and rarely Y. pseudotuberculosis) was the fourth most commonly reported zoonosis in humans in the European Union (EU), with a stable trend in 2014-2019. The CZ reports an incidence up to three times higher but a 2.5 lower share of hospitalized patients compared to the EU average, which probably indicates that the CZ has an effective surveillance system in place. The trend in the incidence of the disease has stagnated in the CZ and the EU in recent years. The most common vehicle for transmission of yersiniosis to humans is contaminated food, especially undercooked pork, less often vegetables or water. Contamination of products from home slaughtered animals intended for private consumption is likely and would also explain the increased incidence of the disease, particularly in the winter months.
Advances in screening and detection of gastric cancer

With an estimated one million new cases and 769 000 deaths in 2020, gastric cancer is the fifth most frequent cancer and fourth leading cause of cancer death globally. Incidence rates are highest in Asia and Eastern Europe. This manuscript will review the current modalities of diagnosis, staging, and screening of gastric cancer. We will also highlight development of novel diagnostics and advancements in endoscopic detection of early gastric cancer.
Spatial, temporal, and space-time clusters associated with opioid and cannabis poisoning events in U.S. dogs (2005–2014)

While a substantial amount of research has focused on the abuse of opioids and cannabinoids in human populations, few studies have investigated accidental poisoning events in pet populations. The objective of this study was to identify whether poisoning events involving opioids and cannabinoids clustered in space, time, and space-time, and compare the locations of clusters between the two toxicants. Data were obtained concerning reports of dog poisoning events from the American Society for the Prevention of Cruelty to Animals’ (ASPCA) Animal Poisoning Control Center (APCC), from 2005–2014. The spatial scan statistic was used to identify clusters with a high proportion of these poisoning events. Our analyses show that opioid and cannabinoid poisoning events clustered in space, time, and space-time. The cluster patterns identified for each toxicant were distinct, but both shared some similarities with human use data. This study may help increase awareness to the public, public health, and veterinary communities about where and when dogs were most affected by opioid and cannabinoid poisonings. This study highlights the need to educate dog owners about safeguarding opioid and cannabinoid products from vulnerable populations.
Organic-Inorganic Composite Electrolytes Optimized with Fluoroethylene Carbonate Additive for Quasi-Solid-State Lithium-Metal Batteries.

Composite solid electrolytes (CSEs) are considered crucial materials for next-generation solid-state lithium batteries with high energy density and reliable safety, and they make full use of the advantages of both organic and inorganic solid-state electrolytes. However, few CSEs have sufficiently high ionic conductivity at room temperature for practical applications. Here, a traditional CSE consisting of poly(ethylene oxide) (PEO) matrix and Li1.3Al0. 3Ti1.7(PO4)3 (LATP) fillers was optimized by introducing a fluoroethylene carbonate (FEC) additive, resulting in an improved high ionic conductivity of 1.99 × 10-4 S cm-1 at 30 °C. The symmetric Li||Li cell assembled with the optimized CSE exhibited a low overpotential and a good cycling stability of more than 1500 h at room temperature. Moreover, the Li||LiFePO4 battery with the optimized CSE delivered a discharge capacity of 132 mAh g-1 at 0.2 C after 300 cycles at room temperature. Comparisons between the LATP-containing CSE and control electrolytes indicated that the enhanced ion conductivity of the former resulted from the synergistic effect of LATP and FEC. Comprehensive characterizations and DFT calculations suggest that with the presence of LATP, FEC additives in the precursor could transform into some other species in the preparation process of CSE. It is believed that these FEC-derived species improve the ion conductivity of the CSEs. The results reported here may open up new approaches to developing composite electrolytes with high ionic conductivity at room temperature by introducing organic additives in the precursor and converting them into species that facilitate ion conduction in the CSE preparation process.
Coupling CRISPR interference with FACS enrichment: New approach in glycoengineering of CHO cell lines for therapeutic glycoprotein production

Difficulties in obtaining and maintaining the desired level of the critical quality attributes (CQAs) of therapeutic proteins as well as the pace of the development are major challenges of current biopharmaceutical development. Therapeutic proteins, both innovative and biosimilars, are mostly glycosylated. Glycans directly influence the stability, potency, plasma half‐life, immunogenicity, and effector functions of the therapeutic. Hence, glycosylation is widely recognized as a process‐dependent CQA of therapeutic glycoproteins. Due to the typically high heterogeneity of glycoforms attached to the proteins, control of glycosylation represents one of the most challenging aspects of biopharmaceutical development. Here, we explored a new glycoengineering approach in therapeutic glycoproteins development, which enabled us to achieve the targeted glycoprofile of the Fc‐fusion protein in a fast manner. Coupling CRISPRi technology with lectin‐FACS sorting enabled downregulation of the endogenous gene involved in fucosylation and further enrichment of CHO cells producing Fc‐fusion proteins with reduced fucosylation levels. Enrichment of cells with targeted glycoprofile can lead to time‐optimized clone screening and speed up cell line development. Moreover, the presented approach allows isolation of clones with varying levels of fucosylation, which makes it applicable to a broad range of glycoproteins differing in target fucosylation level.