Miracle-dz/UniFAR-FTUs huggingface dataset:
Impairment of sympathetic nerve responses by dopa, dopamine and their α‐methyl analogues

Dopa and dopamine reduced the response of the nictitating membrane to postganglionic sympathetic nerve stimulation in cats pretreated with the monoamine oxidase inhibitor pargyline. A similar reduction could be obtained with α‐methyldopa and α‐methyldopamine in untreated cats. The sensitivity of the membrane to injected noradrenaline, α‐methylnoradrenaline or adrenaline was not reduced. The possible mechanism of the anti‐hypertensive action of monoamine oxidase inhibitors and α‐methyldopa is discussed in the light of these findings.
Visit‐to‐visit blood pressure variability and sleep architecture

Visit‐to‐visit blood pressure (BP) variability (BPV) is an independent risk factor of cardiovascular disease (CVD). Sleep architecture characterizes the distribution of different stages of sleep and may be important in CVD development. We examined the association between visit‐to‐visit BPV and sleep architecture using in‐lab polysomnographic data from 3,565 patients referred to an academic sleep center. BPV was calculated using the intra‐individual coefficient of variation of BP measures collected 12 months before the sleep study. We conducted multiple linear regression analyses to assess the association of systolic and diastolic BPV with sleep architecture—rapid eye movement (REM) and non‐rapid eye movement (NREM) sleep duration.
Spontaneous ilio-psoas haematomas (IPHs): a warning for COVID-19 inpatients

Abstract Introduction Critically ill patients with COVID-19 are at increased risk of developing a hypercoagulable state due to haemostatic changes directly related to the SARS-CoV-2 infection or to the consequence of the cytokine storm. Anticoagulation is now recommended to reduce the thrombotic risk. Ilio-psoas haematoma (IPH) is a potentially lethal condition that can arise during the hospitalization, especially in intensive care units (ICUs) and frequently reported as a complication of anticoagulation treatment. Materials and methods We report a case series of seven subjects with SARS-CoV-2 pneumonia complicated by Ilio-psoas haematomas (IPHs) at our COVID-Hospital in Rome, Italy. Results Over the observation period, 925 subjects with confirmed SARS-CoV-2 infection were admitted to our COVID-hospital. Among them, we found seven spontaneous IPHs with an incidence of 7.6 cases per 1000 hospitalization. All the reported cases had a severe manifestation of COVID-19 pneumonia, with at least one comorbidity and 5/7 were on treatment with low weight molecular heparin for micro or macro pulmonary thrombosis. Conclusions Given the indications to prescribe anticoagulant therapy in COVID-19 and the lack of solid evidences on the optimal dose and duration, it is important to be aware of the iliopsoas haematoma as a potentially serious complication in COVID-19 inpatients. KEY MESSAGE Critically ill patients with COVID-19 are at increased risk of hypercoagulability state and anticoagulation therapy is recommended. Ilio-psoas haematoma (IPH) is found to be a complication of anticoagulation regimen especially in severe COVID-19 cases. An incidence of 7.6 cases per 1000 admission of IPHs was reported. Hypoesthesia of the lower limbs, pain triggered by femoral rotation, hypovolaemia and anaemia are the most common symptoms and signs of IPHs that should alert physician.
Composites from Northern Red Oak (Quercus robur) Leaves and Plant Oil-Based Resins

Composite materials were successfully made out of plant oil-based resin and northern red oak (Quercus robur) leaves col- lected in the fall. The viscosities of the bio-based resins (MAESO and MAELO) were suited to high temperature resin transfer mold- ing (RTM) and vacuum-assisted resin transfer molding (VARTM) processing. The leaves have a waxy epidermal surface layer that needs to be dewaxed prior to use in a composite part. We used different treatments (such as benzene-ethanol, boiling water, and strong detergent) to dewax the leaves; all three methods seem to give good results; but boiling water and strong detergent were con- sidered the best treatments for the dewaxing of leaves and boiling water was considered the greenest dewaxing method. The compati- bility between the resin and the leaves was improved with a silane treatment which resulted in composites with higher mechanical stiffness than the resin itself. With 10 wt % leaves, we obtained an improvement in the composite modulus of about 14% from which we could estimate the leaf modulus at about 5.3 GPa. An alternative method to produce biocomposites from leaves without the need for silane treatments consists in carbonizing the leaves first at 215 � C for 12 h, and then at 450 � C for 1 h. The composites made with leaves and bioresins derived from functionalized triglycerides have the potential for use in high volume applications with low costs such as housing, construction, civil infrastructure, toys, and furniture. The use of leaves as a biocomposite filler has several advantages including (a) reduced cost, (b) improved properties of the resin, (c) composites with high bio content, (d) removal of a waste mate- rial with subsequent prevention of burning with attendant health hazards, and (e) interesting design aesthetics for interior and exte- rior decoration. V C 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 127: 18-26, 2013
Neurobehavioral correlates of impaired emotion recognition in pediatric PTSD

Abstract Despite broad evidence suggesting that adversity-exposed youth experience an impaired ability to recognize emotion in others, the underlying biological mechanisms remains elusive. This study uses a multimethod approach to target the neurological substrates of this phenomenon in a well-phenotyped sample of youth meeting diagnostic criteria for posttraumatic stress disorder (PTSD). Twenty-one PTSD-afflicted youth and 23 typically developing (TD) controls completed clinical interview schedules, an emotion recognition task with eye-tracking, and an implicit emotion processing task during functional magnetic resonance imaging )fMRI). PTSD was associated with decreased accuracy in identification of angry, disgust, and neutral faces as compared to TD youth. Of note, these impairments occurred despite the normal deployment of visual attention in youth with PTSD relative to TD youth. Correlation with a related fMRI task revealed a group by accuracy interaction for amygdala–hippocampus functional connectivity (FC) for angry expressions, where TD youth showed a positive relationship between anger accuracy and amygdala–hippocampus FC; this relationship was reversed in youth with PTSD. These findings are a novel characterization of impaired threat recognition within a well-phenotyped population of severe pediatric PTSD. Further, the differential amygdala–hippocampus FC identified in youth with PTSD may imply aberrant efficiency of emotional contextualization circuits.
The relationship of carotid intima-media thickness with anthropometric and metabolic parameters in patients with classic congenital adrenal hyperplasia

Background/aim We aimed to determine the presence of subclinical atherosclerosis using carotid intima-media thickness (CIMT) and biochemical parameters in children and adolescents with congenital adrenal hyperplasia (CAH). Materials and methods Thirty-four patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency on regular glucocorticoid treatment for ≥3 years and 31 healthy subjects were included in the study. The patients were divided into two groups according to the degree of control of the clinic, laboratory, and radiological parameters as a) “uncontrolled” [n= 22; with increased height velocity (HV) standard deviation score (SDS) (≥2 SDS), advanced bone age, serum 17-OH progesterone <2.0 and ≥10.0 ng/mL or androstenedione <0.3 and ≥ 3.0 ng/mL] or b) “controlled” [n= 12; with HV SDS < 2, bone age (BA)/ chronologic age (CA) ratio < 1.2, serum 17-OH progesterone between 2 and 10 ng/mL and androstenedione between 0.3 and 3.0 ng/mL]. Ultrasonographic examination of carotid artery was performed by the same radiologist using a B-mode ultrasound system. Results There was no significant difference between the CAH and control groups in terms of median (IQR) CIMT values [0.47 (0.05) mm and 0.47 (0.07) mm, respectively; p > 0.05]. When subgroup comparisons were done in terms of median (IQR) CIMT values, there was no significant difference among the controlled, uncontrolled, and healthy control groups [0.45 (0.03) mm, 0.47 (0.04) mm, 0.47 (0.07) mm, respectively; p> 0.05]. In addition, CIMT levels were similar according to sex and disease control status. Conclusion In this study, the CIMT values of CAH cases were similar to those of healthy subjects.
Epigenetic reprogramming rewires transcription during the alternation of generations in Arabidopsis

Alternation between morphologically distinct haploid and diploid life forms is a defining feature of most plant and algal life cycles, yet the underlying molecular mechanisms that govern these transitions remain unclear. Here, we explore the dynamic relationship between chromatin accessibility and epigenetic modifications during life form transitions in Arabidopsis. The diploid-to-haploid life form transition is governed by the loss of H3K9me2 and DNA demethylation of transposon-associated cis-regulatory elements. This event is associated with dramatic changes in chromatin accessibility and transcriptional reprogramming. In contrast, the global loss of H3K27me3 in the haploid form shapes a chromatin accessibility landscape that is poised to re-initiate the transition back to diploid life after fertilisation. Hence, distinct epigenetic reprogramming events rewire transcription through major reorganisation of the regulatory epigenome to guide the alternation of generations in flowering plants.
NOTCH signalling in ovarian cancer angiogenesis

The Notch signalling pathway is involved in the new vessel formation process by regulating tip and stalk cells, which are key cells in the sprout formation. This process is essential in both normal ovary and cancer angiogenesis and is regulated by Notch-VEGF crosstalk. Furthermore, Notch has been linked in ovary with stem cell maintenance and epithelial mesenchymal transition processes. Dysregulation of the Notch pathway is frequent in ovarian cancer (OC) and it has been associated with impaired survival and advanced stages or lymph node involvement. Notch also plays a role in chemoresistance to platinum. In this context, this pathway has emerged as an attractive target for precision medicine in OC. Two main targets of this pathway concentrate the clinical development of compounds blocking Notch: gamma secretase and Delta-like ligand 4. Most of the clinical trials including OC patients have been developed in phase I or phase Ib. Despite being in an early phase, both of these compounds, navicixizumab or demcizumab, two monoclonal antibodies targeting Dll4, showed promising efficacy data in platinum-resistant OC patients in recent studies. This review will focus on the mechanisms of the Notch pathway with special interest in angiogenesis regulation and the implication of Notch as a potential therapeutic target in OC.
The effect of proton pump inhibitor uses on outcomes for cancer patients treated with immune checkpoint inhibitors: a meta-analysis

Background Proton pump inhibitors (PPIs) are commonly prescribed for preventing and treating gastrointestinal ulcers. In patients with advanced cancer, it is unclear whether concomitant use of immune checkpoint inhibitors (ICIs) and PPIs could result in poorer outcomes. This study investigates the impact of PPIs on the survival of cancer patients treated with ICIs. Methods PubMed, MEDLINE, EMBASE, and the Cochrane Library databases were searched from January 1, 1970 to June 2, 2020 for studies reporting the prognoses of cancer patients receiving antitumor therapies including ICIs with or without PPIs. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Hazard ratios (HRs) with a 95% confidence interval (CI) were reported to express the effectiveness of ICIs in PPI users compared to non-PPI users, using a random effects model. Results Five studies were identified comprising 1,167 cancer patients. Concomitant use of PPIs with ICIs did not result in statistically significant changes in OS (HR 0.996; 95% CI: 0.486–1.447) and PFS (HR 0.858; 95% CI: 0.388–1.328). Statistical testing suggested heterogeneity among studies. Sensitivity analyses confirmed the stability of our results. Conclusions Concomitant ICI-PPI therapy does not appear to be significantly associated with OS or PFS, and further research on the effect of individual ICIs in different cancer patients is needed.
Metabolic NMR mapping with microgram tissue biopsy

This study explores the potential of profiling a microgram‐scale soft tissue biopsy by NMR spectroscopy. The important elements of high resolution and high sensitivity for the spectral data are achieved through a unique probe, HR‐μMAS, which allowed comprehensive profiling to be performed on microgram tissue for the first time under MAS conditions. Thorough spatially resolved metabolic maps were acquired across a coronal brain slice of rat C6 gliomas, which rendered the delineation of the tumor lesion. The results present a unique ex vivo NMR possibility to analyze tissue pathology that cannot be fully explored by the conventional approach, HR‐MAS and in vivo MRS. Aside from the capability of analyzing a small localized region to track its specific metabolism, it could also offer the possibility to carry out longitudinal investigations on live animals due to the feasibility of minimally invasive tissue excision.
Adsorption of Rhodamine 3B Dye on Saponite Colloidal Particles in Aqueous Suspensions

Absorption and fluorescence spectroscopies were used to study the adsorption of Rhodamine 3B (R3B) dye on Saponite (Sap) particles in aqueous suspensions. Fluorescence data confirmed that the R3B monomer can be adsorbed in the interlayer space and at the water/clay interface of the Sap tactoids. From the evolution of the fluorescence band with the loading and the aging, it was concluded that the internally adsorbed R3B molecules were obtained by the migration of externally adsorbed species. The aggregation of the dye at the clay surfaces was studied by the metachromasy observed in the R3B absorption spectrum, and head-to-tail R3B dimers and trimers were identified. The molecular arrangement for the head-to-tail J-type R3B allows the incorporation of more monomeric units to reach trimers (and higher aggregates), even in the restricted interlayer space of Sap tactoids.
Changes in transcriptome profiling during the acute/subacute phases of contusional spinal cord injury in rats

Background Spinal cord injuries (SCIs), along with subsequent secondary injuries, often result in irreversible damage to both sensory and motor functions. However, a thorough view of the underlying pathological mechanisms of SCIs, especially in a temporal-spatial manner, is still lacking. Methods To obtain a comprehensive, real-time view of multiple subsets of the cellular mechanisms involved in SCIs, we applied RNA-sequencing technology to characterize the temporal changes in gene expression around the lesion site of contusion SCI in rats. First, we identified the differentially expressed genes (DEGs) in contrast to sham controls at 1, 4, and 7 days post SCI. Through bioinformatics analysis, including Pathway analysis, Gene-act-net, and Pathway-act-net, we screened and verified potential key pathways and genes associated with either the acute or subacute stages of SCI pathology. Results The top three overrepresented pathways were associated with cytokine-cytokine receptor interaction, TNF signaling pathway, and cell cycle at day 1; lysosome, cytokine-cytokine receptor interaction, phagosome at day 4; and phagosome, lysosome, cytokine-cytokine receptor interaction at day 7 post injury. Further, we identified uniquely enriched genes at each time point, such as Ccr1 and Nos2 at day 1; as well as Mgst2, and Pla2g3 at 4 and 7 days post-injury. Conclusions Our pathway analysis suggested a transition from inflammatory responses to multiple forms of cell death processes from the acute to subacute stages of SCI. Further, our results revealed a continuous transformation from a more inflammatory to an apoptotic/self-repairing transcriptome following the time-course of SCIs. Our research provides novel insights into the molecular mechanisms of SCI pathophysiology and identifies potential targets for therapeutic intervention after SCI.
Reliability of the application of transvaginal color Doppler ultrasound in the identification of pelvic tumors in women of childbearing age

Background Recently, transvaginal color Doppler ultrasound (TVCDU) has been widely used in the diagnosis of pelvic tumors. This study aimed to assess the reliability of the application of TVCDU in the identification of pelvic tumors in women of childbearing age. Methods The clinical data of 209 patients with pelvic tumors at childbearing age admitted to our hospital from January 2016 to December 2019 were retrospectively analyzed. The ultrasound signs, color Doppler ultrasound score (CDUS), and resistance index (RI) of benign and malignant pelvic tumors diagnosed by TVCDU were analyzed. The value of transabdominal color Doppler ultrasound (TACDU) and TVCDU in the diagnosis of benign and malignant pelvic tumors was calculated. Results There were 150 cases with benign pelvic tumors and 59 cases with malignant tumors. Most benign tumors had an intact capsule and regular shape, were mainly cystic, and were rarely accompanied by ascites; meanwhile, malignant tumors were mostly non-capsular and irregular in shape, mainly solid or cystic, and were often accompanied by ascites. There were significant differences in the above-mentioned ultrasound signs between benign and malignant tumors (P<0.05). The CDUS score of benign pelvic tumors was significantly lower than that of malignant tumors, and the RI value was significantly higher than that of the malignant tumors (P<0.05). The sensitivity, specificity, and accuracy of TACDU in the diagnosis of benign pelvic and malignant tumors were 83.33%, 84.75%, and 83.73%, respectively; and the sensitivity, specificity, and the accuracy of TVCDU in the diagnosis of benign pelvic and malignant tumors were 95.33%, 88.14%, and 93.30%, respectively; thus TVCDU had a superior performance compared to TACDU, especially in sensitivity and accuracy (P<0.05). Conclusions The sensitivity and accuracy of TVCDU in the differential diagnosis of benign pelvic and malignant tumors in women at childbearing age were significantly higher than those of TACDU. The combined application of CDUS and RI can further improve the accuracy in the diagnosis of pelvic tumors.
DNAJC3 deficiency induces β-cell mitochondrial apoptosis and causes syndromic young-onset diabetes.

OBJECTIVE DNAJC3, also known as P58IPK, is an Hsp40 family member that interacts with and inhibits PKR-like ER-localized eIF2α kinase (PERK). Dnajc3 deficiency in mice causes pancreatic β-cell loss and diabetes. Loss-of-function mutations in DNAJC3 cause early-onset diabetes and multisystemic neurodegeneration. The aim of our study was to investigate the genetic cause of early-onset syndromic diabetes in two unrelated patients, and elucidate the mechanisms of β-cell failure in this syndrome. METHODS Whole exome sequencing was performed and identified variants were confirmed by Sanger sequencing. DNAJC3 was silenced by RNA interference in INS-1E cells, primary rat β-cells, human islets, and induced pluripotent stem cell-derived β-cells. β-cell function and apoptosis were assessed, and potential mediators of apoptosis examined. RESULTS The two patients presented with juvenile-onset diabetes, short stature, hypothyroidism, neurodegeneration, facial dysmorphism, hypoacusis, microcephaly and skeletal bone deformities. They were heterozygous compound and homozygous for novel loss-of-function mutations in DNAJC3. DNAJC3 silencing did not impair insulin content or secretion. Instead, the knockdown induced rat and human β-cell apoptosis and further sensitized cells to endoplasmic reticulum stress, triggering mitochondrial apoptosis via the pro-apoptototic Bcl-2 proteins BIM and PUMA. CONCLUSIONS This report confirms previously described features and expands the clinical spectrum of syndromic DNAJC3 diabetes, one of the five monogenic forms of diabetes pertaining to the PERK pathway of the endoplasmic reticulum stress response. DNAJC3 deficiency may lead to β-cell loss through BIM- and PUMA-dependent activation of the mitochondrial pathway of apoptosis.
Surgical Management of Sigmoid Volvulus: A Multicenter Observational Study

Purpose This study aimed to evaluate real-world clinical outcomes from surgically treated patients for sigmoid volvulus. Methods Five tertiary centers participated in this retrospective study with data collected from October 2003 through September 2018, including demographic information, preoperative clinical data, and information on laparoscopic/open and elective/emergency procedures. Outcome measurements included operation time, postoperative hospitalization, and postoperative morbidity. Results Among 74 patients, sigmoidectomy was the most common procedure (n = 46), followed by Hartmann’s procedure (n = 23), and subtotal colectomy (n = 5). Emergency surgery was performed in 35 cases (47.3%). Of the 35 emergency patients, 34 cases (97.1%) underwent open surgery, and a stoma was established for 26 patients (74.3%). Elective surgery was performed in 39 cases (52.7%), including 21 open procedures (53.8%), and 18 laparoscopic surgeries (46.2%). Median laparoscopic operation time was 180 minutes, while median open surgery time was 130 minutes (P < 0.001). Median postoperative hospitalization was 11 days for laparoscopy and 12 days for open surgery. There were 20 postoperative complications (27.0%), and all were resolved with conservative management. Emergency surgery cases had a higher complication rate than elective surgery cases (40.0% vs. 15.4%, P = 0.034). Conclusion Relative to elective surgery, emergency surgery had a higher rate of postoperative complications, open surgery, and stoma formation. As such, elective laparoscopic surgery after successful sigmoidoscopic decompression may be the optimal clinical option.
Decreased expression of AKAP4 and TyrPho proteins in testis, epididymis, and spermatozoa with low sexual performance of mice induced by modified CUMS

The molecular mechanism of chronic stress especially reduced motility, a major cause of male infertility, has not been proved. It is known that A‐kinase anchor protein 4 (AKAP4) and tyrosine‐phosphorylated (TyrPho) proteins are involved in progressive motility. This study aimed to investigate the effect of chronic unpredictable mild stress (CUMS) on sexual behaviours, sperm quality, and expressions of AKAP4 and TyrPho proteins in testis, epididymis, and spermatozoa. Sixteen male mice were divided into control and CUMS groups (n = 8/group). Animals were induced by a stressor from twelve stressors for 36 days. Sexual behaviours, corticosterone and testosterone, sperm parameters, and histopathology were observed. The expressions of AKAP4 and TyrPho proteins in testis, epididymis, and spermatozoa were examined. Results showed that CUMS significantly increased corticosterone while serum testosterone level was decreased. Sexual behaviours and sperm parameter quality were significantly decreased. CUMS mice showed vacuolisation and pyknotic cells in seminiferous epithelium and less sperm mass was observed within epididymal lumen. CUMS decreased expressions of AKAP4 and TyrPho proteins in testis, epididymis, and spermatozoa. In conclusion, the decreased expression of AKAP4 and TyrPho proteins may be a mechanism associated with low semen qualities particularly decrease of sperm motility in CUMS.