Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of four novel variants in the CDH23 gene from four affected families with hearing loss

Background: Hearing loss (HL) is the most common form of sensory disorder in humans. Molecular diagnosis of HL is important for genetic counseling for the affected individuals and their families. Methods: To identify potential genetic causes, we performed whole-exome sequencing and related biomedical informatics for 351 non-syndromic HL patients and their family members. Results: In the present study, we report the identification of four compound heterozygous variants in the CDH23 gene from four affected families, including four novel variants (c.995C>A, p.T332K; c.2159G>A, p.R720Q; c.5534A>G, p.N1845S, and c.7055-1G>C) and two frequently reported variants (c.719C>T, p.P240L and c.4762C>T, p.R1588W). Conclusion: Our findings significantly expanded the mutation spectrum of CDH23-associated autosomal recessive hearing loss.
Single-cell transcriptomic analysis of the tumor ecosystem of adenoid cystic carcinoma

Adenoid cystic carcinoma (ACC) is a malignant tumor that originates from exocrine gland epithelial cells. We profiled the transcriptomes of 49,948 cells from paracarcinoma and carcinoma tissues of three patients using single-cell RNA sequencing. Three main types of the epithelial cells were identified into myoepithelial-like cells, intercalated duct-like cells, and duct-like cells by marker genes. And part of intercalated duct-like cells with special copy number variations which altered with MYB family gene and EN1 transcriptomes were identified as premalignant cells. Developmental pseudo-time analysis showed that the premalignant cells eventually transformed into malignant cells. Furthermore, MYB and MYBL1 were found to belong to two different gene modules and were expressed in a mutually exclusive manner. The two gene modules drove ACC progression into different directions. Our findings provide novel evidence to explain the high recurrence rate of ACC and its characteristic biological behavior.
The impact of digital transformation on corporate sustainability- new evidence from Chinese listed companies

As Industry 4.0 is seen as the core industrial stage for achieving sustainable development, more and more scholars are exploring the practical effects of Industry 4.0. This paper evaluates the impact of digital transformation on business sustainability, explores whether digital transformation breaks down perceptions, and examines the mechanisms by which it works. First, we measured the digital transformation of each firm using textual analysis. and found that the coefficient of digital transformation is 0.006 on corporate sustainability at the 1% significant level. Secondly, we found that digital transformation eases knowledge flow barriers and makes knowledge more accessible to firms. Firms with higher digital transformation attract more skilled people, which can create talent barriers. Digital transformation can exacerbate firms’ industry monopolies, while increasing the proportion of boardroom women and the inclusion of older members sends positive signals to outsiders. Finally, we find that low costs, high labor productivity, high innovation and low cost of sales are important channels for digital transformation. In addition, digital transformation increases the management costs of firms.
Short-term and long-term outcomes in patients with cryptococcal meningitis after ventriculoperitoneal shunt placement

Objective The purpose of this study was to assess the short-term and long-term outcomes of ventriculoperitoneal shunt (VPS) placement in patients with cryptococcal meningitis (CM). Methods We performed a retrospective analysis of all patients with CM admitted to the Peking Union Medical College Hospital from September 1990 to January 2021. We collected related clinical features to analyze the short- and long-term outcomes of VPS at 1 month and 1 year at least the following therapy, respectively. Overall survival (OS) was compared with all patients and a subgroup of critically ill cases by the Kaplan–Meier method with the log-rank test. Univariable and multivariable analyses were also performed using the Cox proportional hazard model to identify statistically significant prognostic factors. Results We enrolled 98 patients, fifteen of whom underwent VPS. Those who received VPS had a lower cerebrospinal fluid (CSF) Cryptococcus burden (1:1 vs. 1:16; p = 0.046), lower opening pressures (173.3 mmH2 O vs. 224 mmH2O; p = 0.009) at lumbar punctures, and a lower incidence of critical cases (6.7 vs. 31.3%; p = 0.049). According to our long-term follow-up, no significant difference was shown in the Barthel Index (BI) between the two groups. Two patients in the VPS group suffered postoperative complications and had to go through another revision surgery. According to survival analysis, overall survival (OS) between the VPS and non-VPS groups was not significantly different. However, the Kaplan–Meier plots showed that critical patients with VPS had better survival in OS (p < 0.009). Multivariable analyses for critical patients showed VPS was an independent prognostic factor. Conclusion A VPS could reduce the intracranial pressure (ICP), decrease the counts of Cryptococcus neoformans by a faster rate and reduce the number of critical cases. The VPS used in critical patients with CM has a significant impact on survival, but it showed no improvement in the long-term Barthel Index (BI) vs. the conservative treatment and could lead to postoperative complications.
QUANTUM COPYING : FUNDAMENTAL INEQUALITIES

How well can one copy an arbitrary qubit? To answer this question we consider two arbitrary vectors in a two-dimensional state space and an abstract copying transformation which will copy these two vectors. If the vectors are orthogonal, then perfect copies can be made. If they are not, then errors will be introduced. The size of the error depends on the inner product of the two original vectors. We derive a lower bound for the amount of noise induced by quantum copying. We examine both copying transformations which produce one copy and transformations which produce many, and show that the quality of each copy decreases as the number of copies increases.
The Tensor Pomeron and Small-x Deep Inelastic Scattering

We apply the tensor-pomeron model to small-$x$ deep-inelastic lepton-proton scattering and photoproduction. Our model includes a soft and a hard tensor pomeron as well as a reggeon contribution. Data with c.m. energies $6 < \sqrt{s} < 318$ GeV and virtualities $Q^2 < 50 \,\mbox{GeV}^2$ are considered. Our fit gives a very good description of the available data in this kinematic region, including the latest HERA data for $x < 0.01$. In particular, the transition region from low to high $Q^2$ is well described. Within the errors, the hard pomeron is absent in photoproduction. The intercepts of the soft and hard pomeron in the two-tensor-pomeron model are found to be $1.0935\, ({}^{+76}_{-64})$ and $1.3008 \,({}^{+73}_{-84})$, respectively. We argue that a vector pomeron would not give any contribution to photoproduction.
Ceramic bone graft substitute (Mg-HA) in spinal fusion: A prospective pilot study

Background: Iliac crest bone graft (ICBG) is considered the gold standard for spine surgical procedures to achieve a successful fusion due to its known osteoinductive and osteoconductive properties. However, complications related to harvesting procedure and donor site morbidity have been largely reported in the literature, favoring the development of a wide range of alternative products to be used as bone graft extenders or substitutes for spine fusion. Among all, ceramic-based biomaterials have been widely studied and employed in the last years as bone graft substitutes. Methods: We report here the results of a prospective pilot study aimed to evaluating the grade of ossification obtained by the use of an Mg-doped hydroxyapatite (HA) product to achieve postero-lateral fusion in degenerative spine diseases. Results: Results show a successful degree of fusion of about 62% at the 12-month follow-up and an improvement of quality of life and health status following surgery, as evaluated by clinical scores (ODI, VAS, and EQ-5L). No adverse events related to the material were reported. Conclusion: The present pilot study shows the effectiveness and the safety profile of an Mg-doped HA bone graft substitute used to achieve postero-lateral fusion in the treatment of degenerative spine diseases, laying down the basis for further larger clinical investigations.
The protective immunity induced by intranasally inoculated serotype 63 chimpanzee adenovirus vector expressing human respiratory syncytial virus prefusion fusion glycoprotein in BALB/c mice

Human respiratory syncytial virus (RSV) is a ubiquitous pediatric pathogen causing serious lower respiratory tract disease worldwide. No licensed vaccine is currently available. In this work, the coding gene for mDS-Dav1, the full-length and prefusion conformation RSV fusion glycoprotein (F), was designed by introducing the stabilized prefusion F (preF) mutations from DS-Cav1 into the encoding gene of wild-type RSV (wtRSV) F protein. The recombinant adenovirus encoding mDS-Cav1, rChAd63-mDS-Cav1, was constructed based on serotype 63 chimpanzee adenovirus vector and characterized in vitro. After immunizing mice via intranasal route, the rChAd63-mDS-Cav1 induced enhanced neutralizing antibody and F-specific CD8+ T cell responses as well as good immune protection against RSV challenge with the absence of enhanced RSV disease (ERD) in BALB/c mice. The results indicate that rChAd63-mDS-Cav1 is a promising mucosal vaccine candidate against RSV infection and warrants further development.
Semi-analytic derivation of the threshold mass for prompt collapse in binary neutron-star mergers

The threshold mass for prompt collapse in binary neutron-star (NS) mergers was empirically found to depend on the stellar properties of the maximum-mass non-rotating NS model. Here, we present a semi-analytic derivation of this empirical relation, which suggests that it is rather insensitive to thermal effects, to deviations from axisymmetry and to the exact rotation law in merger remnants. We utilize axisymmetric, cold equilibrium models with differential rotation and determine the threshold mass for collapse from the comparison between an empirical relation that describes the angular momentum in the remnant for a given total binary mass and the sequence of rotating equilibrium models at the threshold to collapse (the latter assumed to be near the turning point of fixed-angular-momentum sequences). In spite of the various simplifying assumptions, the empirical relation for prompt collapse is reproduced with good accuracy, which demonstrates its robustness. We discuss implications of our methodology and results for understanding other empirical relations satisfied by NS merger remnants that have been discovered by numerical simulations and that play a key role in constraining the high-density equation of state through gravitational-wave observations.
Glass-induced enhancement of superconducting 
Tc
: Pairing via dissipative mediators

With substantial evidence of glassy behavior in the phase diagram of high $T_c$ superconductors and its co-existence with superconductivity, we attempt to answer the question: what are the properties of a superconducting state where the force driving cooper pairing becomes dissipative? We find that when the bosonic mediator is local, dissipation acts to reduce the superconducting critical temperature ($T_c$). On the other hand, contrary to na\"{i}ve expectations, $T_c$ behaves non-monotonically with dissipation for a non-local mediator -- weakly dissipative bosons at different energy scales act coherently to give rise to an increase in $T_c$ and eventually destroy superconductivity when the dissipation exceeds a critical value. The critical value occurs when dissipative effects become comparable to the energy scale associated with the spatial stiffness of the mediator, at which point, $T_c$ acquires a maximum. We outline consequences of our results to recent proton irradiation experiments (M. Leroux et al.,~\cite{Welp2018}) on the cuprate superconductor La$_{2-x}$Ba$_x$CuO$_4$ (LBCO) which observe a disorder induced increase in $T_c$ even when the transition temperature of the proximate charge density wave (CDW) is unaffected by the presence of irradiation. Our mechanism is a novel way to raise $T_c$ that does not require a `tug-of-war' -type scenario between two competing phases.
Case report: Tunneling foreign body in the metatarsal bones of a dog

A 2-year-old male intact goldendoodle presented for intermittent lameness, persistent draining tracts, and radiographic identified boney lytic lesions involving the metatarsal region, which had persisted for approximately 8 months before presentation to our referral hospital. Radiographic and computed tomography (CT) images suggested a tubular structure encircling and tunneling through the right metatarsal bones. Exploratory surgery confirmed a circumferential rubber band foreign body, with lytic boney tunneling within the metatarsal bones. CT provided vital information to assist in the surgical planning for this patient with a chronic tunneling foreign body.
Iron-folic acid adherence and associated factors among pregnant women attending antenatal care at Metema District, Northwest Ethiopia

Background Iron deficiency accounts for about half of anemia cases worldwide. Iron and folate supplementation can effectively control and prevent anemia during pregnancy. Despite the efforts to reduce iron deficiency anemia during pregnancy, only a few women took an iron supplement as recommended. The aim of this study is to assess adherence to iron-folic acid supplementation and associated factors. Methods A facility-based cross-sectional study was conducted from April 1 to May 31, 2021, among pregnant women attending the antenatal care clinic at Metema district governmental health institutions. Data was collected through face-to-face interviews with an interviewer-administered questionnaire. Epi info version 7.1 and SPSS 20 were used for data entry and analysis. Binary logistic regression analysis was done to identify factors associated with iron-folic acid supplementation for pregnant women. Significant associations were determined based on the adjusted odds ratio (AOR) and 95% confidence, with a p-value < 0.05. Results The proportion of pregnant women adhering to iron-folic acid supplementation was 34.9% (95% CI: 31, 38.8%). Maternal educational status [AOR = 6.09, 95% CI (3.26, 11.4)], time of first antenatal consultation [AOR = 1.95, 95% CI (1.25, 3.06)], having good knowledge of iron with folic acid supplementation [AOR = 2.80, 95% CI (1.83, 4.28)], having a good understanding of anemia [AOR = 1.61, 95% CI (1.06, 2.43)], and a history of anemia during current pregnancy [AOR = 2.31, 95% CI (1.36, 3.94)] were factors affecting iron-folic acid supplementation adherence. Conclusions Iron-folic acid supplementation adherence was low in the study area. Increasing maternal awareness, having good knowledge about the benefits of iron-folate supplements, and early registration to antenatal care were positive determinants of iron with folic acid adherence.
Impacts of vitamin A deficiency on biological rhythms: Insights from the literature

Vitamin A is essential for brain function, in addition to its important roles in vision, immunity, and reproduction. Previous studies have shown that retinoic acid (RA), the bioactive form of vitamin A, is involved in the regulation of various intracellular responses related to biological rhythms. RA is reported to affect the circadian rhythm by binding to RA receptors, such as receptors in the circadian feedback loops in the mammalian suprachiasmatic nucleus. However, evidence of the impacts of vitamin A deficiency (VAD) on biological rhythms is limited, and most of the related studies were conducted on animals. In this review, we described the physiological functions of biological rhythms and physiological pathways/molecular mechanisms regulating the biological rhythms. We then discussed the current understanding of the associations of VAD with biological rhythm disorders/diseases (sleep disorders, impairments in learning/memory, emotional disorders, and other immune or metabolism diseases) and summarized the currently proposed mechanisms (mainly by retinoid nuclear receptors and related proteins) for the associations. This review may help recognize the role of VAD in biological rhythm disorders and stimulate clinical or epidemiological studies to confirm the findings of related animal studies.
Regulation of piglet T-cell immune responses by thioredoxin peroxidase from Cysticercus cellulosae excretory-secretory antigens

Taenia solium (T. solium) cysticercosis is a serious threat to human health and animal husbandry. During parasitization, Cysticercus cellulosae (C. cellulosae) can excrete and secrete antigens that modulate the host’s T-cell immune responses. However, the composition of C. cellulosae excretory-secretory antigens (ESAs) is complex. This study sought to identify the key molecules in C. cellulosae ESAs involved in regulating T-cell immune responses. Thus, we screened for thioredoxin peroxidase (TPx), with the highest differential expression, as the key target by label-free quantification proteomics of C. cellulosae and its ESAs. In addition, we verified whether TPx protein mainly exists in C. cellulosae ESAs. The TPx recombinant protein was prepared by eukaryotic expression, and ESAs were used as the experimental group to further investigate the effect of TPx protein on the immune response of piglet T cells in vitro. TPx protein induced an increase in CD4+ T cells in piglet peripheral blood mononuclear cells (PBMCs), while CD8+ T cells did not change significantly. This resulted in an imbalance in the CD4+/CD8+ T-cell ratio and an increase in CD4+CD25+Foxp3+ Treg cells in the PBMCs. In addition, TPx protein initiated T helper 2 (Th2)-type immune responses by secreting IL-4 and IL-10 and suppressed Th1/Th17-type immune responses. The results showed that ESAs were involved in regulating piglet T-cell immune responses cells. This suggests that TPx protein found in ESAs plays an essential role to help the parasite evade host immune attack. Moreover, this lays a foundation for the subsequent exploration of the mechanism through which TPx protein regulates signaling molecules to influence T-cell differentiation.
Image discrimination reversal learning is impaired by sleep deprivation in rats: Cognitive rigidity or fatigue?

Introduction Insufficient sleep is pervasive worldwide, and its toll on health and safety is recapitulated in many settings. It is thus important to understand how poor sleep affects the brain and decision making. A robust literature documents the adverse effects of sleep deprivation on cognitive processes including cognitive flexibility, which is the capacity to appraise new feedback and make behavioral adjustments to respond appropriately. Animal models are often used to unravel the molecules, genes and neural circuits that are altered by sleep loss. Herein we take a translational approach to model the effects of sleep deprivation on cognitive rigidity, i.e., impaired cognitive flexibility in rats. Methods There are several approaches to assess cognitive rigidity; in the present study, we employ a pairwise discrimination reversal task. To our knowledge this is the first time this paradigm has been used to investigate sleep deprivation. In this touchscreen operant platform, we trained rats to select one of two images to claim a sucrose pellet reward. If the non-rewarded image was selected the rats proceeded to a correction trial where both images were presented in the same position as before. This image presentation continued until the rat selected the correct image. Once rats reached performance criteria, the reward contingencies were reversed. In one group of rats the initial reversal session was preceded by 10 h of sleep deprivation. We compared those rats to controls with undisturbed sleep on the number of sessions to reach performance criteria, number of trials per session, response latencies, correct responses, errors, perseverative errors and perseveration bouts in the initial training and reversal phases. Results We report that on reversal session one, sleep deprived rats completed a fraction of the trials completed by controls. On subsequent reversal sessions, the sleep deprived rats struggled to adapt to the reversed contingencies despite completing a similar number of trials, suggesting an effect of cognitive rigidity separate from fatigue. Discussion We discuss the delayed performance dynamics incurred by sleep loss in the context of fatigue and the implications of using pairwise discrimination reversal as a model to further examine the effects of sleep loss on adaptive decision making.
Influence of nutrients and metabolites on the differentiation of plasma cells and implications for autoimmunity

The modulation of inflammatory (auto)immune reactions by nutrients and gut bacterial metabolites is of great interest for potential preventive and therapeutic strategies. B cell-derived plasma cells are major players in inflammatory (auto)immune responses and can exhibit pro- or anti-inflammatory effects through (auto)antibody-dependent and -independent functions. Emerging evidence indicates a key role of nutrients and microbial metabolites in regulating the differentiation of plasma cells as well as their differentiation to pro- or anti-inflammatory phenotypes. These effects might be mediated indirectly by influencing other immune cells or directly through B cell-intrinsic mechanisms. Here, we provide an overview of nutrients and metabolites that influence B cell-intrinsic signaling pathways regulating B cell activation, plasma cell differentiation, and effector functions. Furthermore, we outline important inflammatory plasma cell phenotypes whose differentiation could be targeted by nutrients and microbial metabolites. Finally, we discuss possible implications for inflammatory (auto)immune conditions.
Development of sequencing-based methodologies to distinguish viable from non-viable cells in a bovine milk matrix: A pilot study

Although high-throughput DNA sequencing-based methods have been of great value for determining the composition of microbial communities in various environments, there is the potential for inaccuracies arising from the sequencing of DNA from dead microorganisms. In this pilot study, we compared different sequencing-based methods to assess their relative accuracy with respect to distinguishing between viable and non-viable cells, using a live and heat-inactivated model community spiked into bovine milk. The methods used were shotgun metagenomics with and without propidium monoazide (PMA) treatment, RNA-based 16S rRNA sequencing and metatranscriptomics. The results showed that methods were generally accurate, though significant differences were found depending on the library types and sequencing technologies. Different molecular targets were the basis for variations in the results generated using different library types, while differences in the derived composition data from Oxford Nanopore Technologies-and Illumina-based sequencing likely reflect a combination of different sequencing depths, error rates and bioinformatics pipelines. Although PMA was successfully applied in this study, further optimisation is required before it can be applied in a more universal context for complex microbiomes. Overall, these methods show promise and represent another important step towards the ultimate establishment of approaches that can be applied to accurately identify live microorganisms in milk and other food niches.