Miracle-dz/UniFAR-FTUs huggingface dataset:
Knockdown of astrocytic Grin2a aggravates β‐amyloid‐induced memory and cognitive deficits through regulating nerve growth factor

Synapse degeneration correlates strongly with cognitive impairments in Alzheimer's disease (AD) patients. Soluble Amyloid‐beta (Aβ) oligomers are thought as the major trigger of synaptic malfunctions. Our earlier studies have demonstrated that Aβ oligomers interfere with synaptic function through N‐methyl‐D‐aspartate receptors (NMDARs). Our recent in vitro study found the neuroprotective role of astrocytic GluN2A in the promotion of synapse survival and identified nerve growth factor (NGF) derived from astrocytes, as a likely mediator of astrocytic GluN2A buffering against Aβ synaptotoxicity. Our present in vivo study focused on exploring the precise mechanism of astrocytic GluN2A influencing Aβ synaptotoxicity through regulating NGF. We generated an adeno‐associated virus (AAV) expressing an astrocytic promoter (GfaABC1D) shRNA targeted to Grin2a (the gene encoding GluN2A) to perform astrocyte‐specific Grin2a knockdown in the hippocampal dentate gyrus, after 3 weeks of virus vector expression, Aβ were bilaterally injected into the intracerebral ventricle. Our results showed that astrocyte‐specific knockdown of Grin2a and Aβ application both significantly impaired spatial memory and cognition, which associated with the reduced synaptic proteins PSD95, synaptophysin and compensatory increased NGF. The reduced astrocytic GluN2A can counteract Aβ‐induced compensatory protective increase of NGF through regulating pNF‐κB, Furin and VAMP3, which modulating the synthesis, mature and secretion of NGF respectively. Our present data reveal, for the first time, a novel mechanism of astrocytic GluN2A in exerting protective effects on synapses at the early stage of Aβ exposure, which may contribute to establish new targets for AD prevention and early therapy.
Pioneer neutrophils release chromatin within in vivo swarms

Neutrophils are rapidly recruited to inflammatory sites where their coordinated migration forms clusters, a process termed neutrophil swarming. The factors that modulate early stages of neutrophil swarming are not fully understood, requiring the development of new in vivo models. Using transgenic zebrafish larvae to study endogenous neutrophil migration in a tissue damage model, we demonstrate that neutrophil swarming is a conserved process in zebrafish immunity, sharing essential features with mammalian systems. We show that neutrophil swarms initially develop around an individual pioneer neutrophil. We observed the violent release of extracellular cytoplasmic and nuclear fragments by the pioneer and early swarming neutrophils. By combining in vitro and in vivo approaches to study essential components of neutrophil extracellular traps (NETs), we provide in-depth characterisation and high-resolution imaging of the composition and morphology of these release events. Using a photoconversion approach to track neutrophils within developing swarms, we identify that the fate of swarm-initiating pioneer neutrophils involves extracellular chromatin release and that the key NET components gasdermin, neutrophil elastase, and myeloperoxidase are required for the swarming process. Together our findings demonstrate that release of cellular components by pioneer neutrophils is an initial step in neutrophil swarming at sites of tissue injury.
COVID-Associated Pulmonary Aspergillosis in the United States: Is It Rare or Have We Missed the Diagnosis?

While the incidence of COVID-associated pulmonary aspergillosis (CAPA) in COVID-19 patients admitted to the ICU in Europe is widely published (incidence up to 30%) (1), data on CAPA from the United States is lacking or has not been well described (2, 3). ….
Comparison of mtDNA control region among descendant breeds of the extinct Zaupel sheep revealed haplogroup C and D in Central Europe

Abstract The consideration of the descendance is indispensable in the preservation of endangered animal breeds. The authors compared mitochondrial DNA (mtDNA) control region sequence in three descendant breeds of the extinct Zaupel sheep, firstly. Their investigation was carried out in order to prove the common origin of Waldschaf (Austria), Bovec sheep (Slovenia) and Cikta (Hungary). A total of 118 biological samples were taken from non‐related representatives of the three breeds between 2015 and 2017. A newly designed primer pair was also used to amplify the segment (1180 bp) to be tested. The total number of haplotypes in the whole study population was 49. The majority of which fell into haplogroup B. The significant negative value of the Fu's Fs statistic (Fs statistic = −3.296, p = 0.013) based on haplotype frequencies demonstrated a moderate foreign gene flow. As a novel observation haplogroups C and D appeared in Cikta and Bovec sheep, respectively. The Tajima D‐test value in the entire study population was −0.914 (p > 0.10), meaning that the separation of the three descendant breeds did not cause genetic drift, these are collectively in genetic equilibrium. The genetic information confirmed the common origin of the breeds known from the breed history.
Videos improve patient understanding of chemotherapy terminology in a rural setting

It is critical patients understand the terms used to describe oncology treatments; however, even basic chemotherapy terminology can be misunderstood. Rural communities tend to have especially low levels of health literacy compared with nonrural communities. To address low health literacy in rural communities, this study tested rural participants' understanding of previously developed educational chemotherapy videos that were designed for an underserved urban population. Participants were also asked for feedback to determine if the videos could be improved.
The role of non‐coding RNAs in drug resistance of oral squamous cell carcinoma and therapeutic potential

Oral squamous cell carcinoma (OSCC), the eighth most prevalent cancer in the world, arises from the interaction of multiple factors including tobacco, alcohol consumption, and betel quid. Chemotherapeutic agents such as cisplatin, 5‐fluorouracil, and paclitaxel have now become the first‐line options for OSCC patients. Nevertheless, most OSCC patients eventually acquire drug resistance, leading to poor prognosis. With the discovery and identification of non‐coding RNAs (ncRNAs), the functions of dysregulated ncRNAs in OSCC development and drug resistance are gradually being widely recognized. The mechanisms of drug resistance of OSCC are intricate and involve drug efflux, epithelial‐mesenchymal transition, DNA damage repair, and autophagy. At present, strategies to explore the reversal of drug resistance of OSCC need to be urgently developed. Nano‐delivery and self‐cellular drug delivery platforms are considered as effective strategies to overcome drug resistance due to their tumor targeting, controlled release, and consistent pharmacokinetic profiles. In particular, the combined application of new technologies (including CRISPR systems) opened up new horizons for the treatment of drug resistance of OSCC. Hence, this review explored emerging regulatory functions of ncRNAs in drug resistance of OSCC, elucidated multiple ncRNA‐meditated mechanisms of drug resistance of OSCC, and discussed the potential value of drug delivery platforms using nanoparticles and self‐cells as carriers in drug resistance of OSCC.
Associations between prepregnancy body mass index, gestational weight gain and weight catch‐up in small‐for‐gestational‐age children

Abstract Inadequate gestational weight gain (GWG) was related with a higher incidence of small‐for‐gestational‐age (SGA) births than appropriate GWG; however, the long‐term association of maternal GWG with weight catch‐up growth in SGA children remains unknown. The objective of this study is to evaluate the associations between prepregnancy body mass index (pBMI), GWG and weight catch‐up patterns in SGA children. Data were from the Collaborative Perinatal Project, an American multicentre prospective cohort study. A total of 56,990 gravidas were recruited at the first prenatal visit, and children were followed up until school age. Maternal pBMI, GWG and physical growth of the offspring at birth, 4 months, 1 year, 4 years and 7 years old were recorded. The latent class analysis was employed to form weight catch‐up growth patterns (appropriate, excessive, slow, regression and no catch‐up patterns) in SGA children. SGA children who developed the ‘appropriate catch‐up growth’ pattern and whose mothers had appropriate pBMI and GWG were chosen as the reference. Associations between GWG for different pBMI and weight catch‐up patterns were analysed by multivariate logistic regression models. A total of 1619 infants (9.45%) were born term SGA. After adjusting for relevant confounders, compared with SGA children whose mothers had appropriate pBMI and GWG, SGA children with maternal prepregnancy underweight (for inadequate GWG, GWG below recommendations, adjusted OR: 2.88, 95% CI: 1.13–7.31; for appropriate/excessive GWG, adjusted OR: 3.07, 95% CI: 1.74–5.42) or with prepregnancy normal weight but inadequate GWG (adjusted OR: 2.14, 95% CI: 1.36–3.38) were at a higher risk of having the ‘no catch‐up growth’ pattern. We suggest that SGA children with maternal prepregnancy underweight or inadequate GWG tend to have a poor weight catch‐up growth at least until school age.
The effect of RNA polymerase V on 24-nt siRNA accumulation depends on DNA methylation contexts and histone modifications in rice

Significance Rice RNA polymerase V (Pol V) influences the accumulation of 24-nucleotide small interfering RNAs (24-nt siRNAs) in a locus-specific manner. Accumulation of 24-nt siRNAs is dependent on Pol V on loci with high CHH methylation levels, low CG and CHG methylation levels, and high active histone modifications. In contrast, a low methylation level in the CHH context, high methylation levels in CG and CHG contexts, and enrichment of repressive histone modifications predispose 24-nt siRNA accumulation to be independent of Pol V. DNA methylation is essential for 24-nt siRNA biosynthesis on Pol V–dependent loci but not on Pol V–independent loci. Our results suggest that monocot Pol V–transcribed scaffold RNAs are essential for reproductive development and 24-nt siRNA biosynthesis on euchromatin. RNA-directed DNA methylation (RdDM) functions in de novo methylation in CG, CHG, and CHH contexts. Here, we performed map-based cloning of OsNRPE1, which encodes the largest subunit of RNA polymerase V (Pol V), a key regulator of gene silencing and reproductive development in rice. We found that rice Pol V is required for CHH methylation on RdDM loci by transcribing long noncoding RNAs. Pol V influences the accumulation of 24-nucleotide small interfering RNAs (24-nt siRNAs) in a locus-specific manner. Biosynthesis of 24-nt siRNAs on loci with high CHH methylation levels and low CG and CHG methylation levels tends to depend on Pol V. In contrast, low methylation levels in the CHH context and high methylation levels in CG and CHG contexts predisposes 24-nt siRNA accumulation to be independent of Pol V. H3K9me1 and H3K9me2 tend to be enriched on Pol V–independent 24-nt siRNA loci, whereas various active histone modifications are enriched on Pol V–dependent 24-nt siRNA loci. DNA methylation is required for 24-nt siRNAs biosynthesis on Pol V–dependent loci but not on Pol V–independent loci. Our results reveal the function of rice Pol V for long noncoding RNA production, DNA methylation, 24-nt siRNA accumulation, and reproductive development.
Gene expression changes in male and female rhesus macaque 60 days after irradiation

Purpose Transcriptome changes can be expected in survivors after lethal irradiation. We aimed to characterize these in males and females and after different cytokine treatments 60 days after irradiation. Material and methods Male and female rhesus macaques (n = 142) received a whole-body exposure with 700 cGy, from which 60 animals survived. Peripheral whole blood was drawn pre-exposure and before sacrificing the surviving animals after 60 days. Results We evaluated gene expression in a three-phase study design. Phase I was a whole-genome screening (NGS) for mRNAs using five pre- and post-exposure RNA samples from both sexes (n = 20). Differential gene expression (DGE) was calculated between samples of survivors and pre-exposure samples (reference), separately for males and females. 1,243 up- and down-regulated genes were identified with 30–50% more deregulated genes in females. 37 candidate mRNAs were chosen for qRT-PCR validation in phase II using the remaining samples (n = 117). Altogether 17 genes showed (borderline) significant (t-test) DGE in groups of untreated or treated animals. Nine genes (CD248, EDAR, FAM19A5, GAL3ST4, GCNT4, HBG2/1, LRRN1, NOG, SYT14) remained with significant changes and were detected in at least 50% of samples per group. Panther analysis revealed an overlap between both sexes, related to the WNT signaling pathway, cell adhesion and immunological functions. For phase III, we validated the nine genes with candidate genes (n = 32) from an earlier conducted study on male baboons. Altogether 14 out of 41 genes showed a concordantly DGE across both species in a bilateral comparison. Conclusions Sixty days after radiation exposure, we identified (1) sex and cytokine treatment independent transcriptional changes, (2) females with almost twice as much deregulated genes appeared more radio-responsive than males, (3) Panther analysis revealed an association with immunological processes and WNT pathway for both sexes.
Breakthrough Infections of SARS-CoV-2 Gamma Variant in Fully Vaccinated Gold Miners, French Guiana, 2021

An outbreak of severe acute respiratory syndrome coronavirus 2 caused by the Gamma variant of concern infected 24/44 (55%) employees of a gold mine in French Guiana (87% symptomatic, no severe forms). The attack rate was 60% (15/25) among fully vaccinated miners and 75% (3/4) among unvaccinated miners without a history of infection.
Cytokine‐induced apoptosis inhibitor 1 (CIAPIN1) accelerates vascular remodelling via p53 and JAK2‐STAT3 regulation in vascular smooth muscle cells

Abnormal vascular smooth muscle cell (VSMC) proliferation and migration lead to neointima formation, which eventually results in cardiovascular hyperplastic diseases. The molecular mechanisms underlying these cellular processes have not been fully understood. Cytokine‐induced apoptosis inhibitor 1 (CIAPIN1) has been identified as an anti‐apoptotic molecule, but little is known about its target genes and related pathways in VSMC dysfunction or its clinical implication in neointima formation following vascular injury.
Robotic Kidney Transplant: The Modern Era Technical Revolution

Since the mid 20th century, transplantation has been a fast-developing field of contemporary medicine. The technical aspects of transplant operations were developed in the 1950s, with little significant change for >50 y. Those techniques allowed completion of various organ transplants and successful patient outcomes, but they also carried the inherent disadvantages of open surgery, such as postoperative pain, wound complications and infections, and prolonged length of hospital stay. The introduction and adoption of minimally invasive surgical techniques in the early 1990s to various surgical specialties including general, gynecologic, and urologic surgery led to significant improvements in postoperative patient care and outcomes. Organ transplantation, with its precision demanding vascular anastomoses, initially had been considered infeasible to accomplish with conventional laparoscopic devices. The institution of robotic surgical technology in the late 1990s and its subsequent wide utilization in fields of surgery changed its accessibility and acceptance. With the steady camera, 3D views, and multidirectional wrist motions, surgical robotics opened new horizons for technically demanding surgeries such as transplantation to be completed in a minimally invasive fashion. Furthermore, the hope was this technique could find a niche to treat patients who otherwise are not deemed surgical candidates in many fields including transplantation. Here in, robotics in kidney transplantation and its ability to help provide equity through access to transplantation will be discussed.
Local IP3 receptor–mediated Ca2+ signals compound to direct blood flow in brain capillaries

Brain capillary calcium signaling controls blood flow. Healthy brain function depends on the finely tuned spatial and temporal delivery of blood-borne nutrients to active neurons via the vast, dense capillary network. Here, using in vivo imaging in anesthetized mice, we reveal that brain capillary endothelial cells control blood flow through a hierarchy of IP3 receptor–mediated Ca2+ events, ranging from small, subsecond protoevents, reflecting Ca2+ release through a small number of channels, to high-amplitude, sustained (up to ~1 min) compound events mediated by large clusters of channels. These frequent (~5000 events/s per microliter of cortex) Ca2+ signals are driven by neuronal activity, which engages Gq protein–coupled receptor signaling, and are enhanced by Ca2+ entry through TRPV4 channels. The resulting Ca2+-dependent synthesis of nitric oxide increases local blood flow selectively through affected capillary branches, providing a mechanism for high-resolution control of blood flow to small clusters of neurons.
Free double‐paddle posterior tibial artery perforator flap for hypopharynx reconstruction: A case report and literature review

Microsurgical free tissue transfer is nowadays considered to be one of the main options for head and neck reconstruction. The free posterior tibial artery perforator (PTAP) flap is a well‐known reconstructive technique for local defect coverage in the distal leg, and only recently has been employed for head and neck reconstructions. Being a very thin and pliable flap, with low donor site morbidity and constant anatomy, the PTA perforator‐based flap could be a great alternative to the more commonly‐employed radial forearm free flap (RFFF). The present case report shows a complex head and neck defect coverage by means of a free double‐paddle PTA flap, with a concise literature review of previous PTA flap descriptions in this setting. A 59‐year‐old male patient presented with a hypopharynx leakage after radiotherapy due to hypopharynx carcinoma. Since the patient had an occluded ulnar artery on the left side and an arterial line in the radial artery on the right side, both a RFFF and an ulnar artery perforator (UAP) flap were contraindicated. Moreover, two different cutaneous flaps were needed to reconstruct a 6 × 8 cm2 defect, one for the reconstruction of the hypopharynx and one for the resurfacing of the neck, since previous surgeries and radiotherapy led to severe fibrosis of the neck. The patient had a BMI of 25.4 kg/m2, which led us to exclude the anterolateral thigh (ALT) flap because of its thickness. For the forementioned reasons, an unconventional double‐paddle PTAP flap based on two perforator vessels was chosen. Based on two perforators, two skin islands were harvested, building a double‐paddle PTA perforator‐based flap. The proximal skin island was 6 × 7 cm2 and the distal one was 6 × 4 cm2. The larger skin flap was set at the leakage of the hypopharynx. The smaller skin island was used to monitor the survival of the whole flap and for resurfacing the outer side of the neck. The postoperative course was uneventful and at 3 months follow up the reconstructive result was good with no functional drawback. In view of the obtained result, we can consider that the PTA flap might be a reliable alternative to the much widely used RFFF, with a minor donor site morbidity, for delicate head and neck reconstructions.
How many parents regret having children and how it is linked to their personality and health: Two studies with national samples in Poland

Surveys conducted over the last few years on representative samples in the US and Germany suggest that the percentage of parents who regret having children is approximately 17–8%. In none of these studies did the researchers attempt a detailed examination of this group of parents from the perspective of their psychological functioning. In the present article, two studies based on large, national samples (N = 1175 and N = 1280), one of which was a representative sample of young Poles, are presented. The results obtained show that the percentage of parents who regret parenthood is higher in Poland than in the US or Germany, and that parents who regret having children are characterized by a higher level of adverse childhood experiences, have poorer psychological and somatic health, are more vulnerable to social evaluation, and experience strong parental identity crisis and parental burnout. Regretting parenthood also turns out to be associated with the parent’s financial situation and marital status, and with having children with special needs. The results indicate that regretting becoming a parent is an important social and psychological issue that should become an object of interest for researchers from various disciplines and for social policy authorities.
A meta-analysis of the effects of social-cognitive training in schizophrenia: The role of treatment characteristics and study quality.

OBJECTIVES This meta-analysis was designed to assess the effects of social-cognitive training (SCT) and whether study quality, treatment approach, treatment context, and sample characteristics influence these effects. METHODS Electronic databases were searched up to 5 August 2020 using variants of keywords: 'social cognition', 'training', 'rehabilitation', 'remediation', and 'schizophrenia'. Methodological moderators were extracted through the Clinical Trials Assessment Measure and verified by authors. This study was pre-registered on PROSPERO (CRD42020154026). RESULTS Forty-two controlled trials with 1,868 participants were identified. The meta-analysis revealed moderate effects on emotion recognition, mental state attribution, and social perception. No significant effects were evident on psychiatric symptoms or social functioning. A small signal was evident for the generalization of treatment gains to executive function. Moderator analyses revealed that studies of lower methodological quality reported larger effects, and samples with lower mean years of education were associated with larger effects of SCT on mental state attribution. Treatment effects did not differ by other moderator variables such as treatment context and intervention types. CONCLUSIONS SCT benefits people with schizophrenia on a variety of social-cognitive outcomes. Differences in baseline symptoms, gender distribution, antipsychotic medication dose, IQ, and other sample features did not create barriers to treatment benefits. Future studies should aim to enhance the generalization of training effects on broader clinical outcomes.