Miracle-dz/UniFAR-FTUs huggingface dataset:
More on: How Do You Boost Resilience During the Current COVID-19 Pandemic in Your Practice?

Wearing a tight-fitting, difficult-to-breathe-through mask and a steamed-up visor as part of our personal protective equipment, together with the constant fear of catching this life-threatening infection, can induce a feeling of anxiety in the sanest of individuals. According to my psychiatrist colleagues, this stress is causing some normally anxious medical and nursing staff to become psychotic. Fortunately, there is reasonable evidence that acupuncture might be of some help. Pilkington and colleagues and Errington–Evans have each reviewed published trials on acupuncture for anxiety, finding positive results in most trials, although neither review could draw firm conclusions due to low methodological research quality of the studies concerned. Formerly, in my pain-clinic practice, I found that most of my patients had an element of anxiety related to constant pain, poor sleeping, fear of incapacity and job loss. After a session or two of acupuncture most of these patients would report feeling calmer, with reduction in anxiety and improved sleep patterns, even if their chronic pain had shown little change in intensity—they just did not worry about that pain so much. I had treated most patients with electroacupuncture (EA) in dense–disperse mode at frequencies of 2/100 Hz. So, the calming effect was probably due to endogenous opioid and serotonin boost from the EA. For those anxious patients in my pain clinic with whom I was not otherwise using EA stimulation, I would add the EA at LI 4 and LI 11. This seemed to be effective. However, after discussion at a national acupuncture symposium, I was persuaded to try the Four Wise Men, Sishencong. To my surprise, patients claimed enhanced benefit and would insist on my using it with every treatment, as they found the improved sleep, and the antianxiety and antistress effects so good that their quality of life (QoL) seemed improved as a result. Occasionally, this was quite dramatic.
Abstract 5387: Integrative analysis of transcriptomic and metabolomic data reveals a critical role for aminosugar metabolism in prostate cancer.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Prostate Cancer is the second most common cause of cancer-related death in men in the US. Like other tumors, prostate cancer development and progression is dictated by multiple molecular events that include changes in levels of genes, transcripts, proteins and metabolites. To better understand the biology of prostate cancer development it is essential to integrate these disparate yet related datasets. Our laboratory has identified matched transcriptomic, proteomic and metabolomic changes in localized prostate cancer relative to adjacent benign tissue as well in metastatic disease compared to organ-confined tumor. To study this using a System's Biology approach we have recently embarked on a pilot study aimed at integrating transcriptomic and metabolomic data to obtain biochemical pathways that key to prostate cancer development. Using an in-house network-based enrichment strategy, amino sugar metabolism was found to be significantly enriched in organ-confined prostate cancer but not in metastatic disease. Amino sugar metabolism describes the utilization of glucose-derived carbon and amino acid (mostly glutamine)-derive nitrogen to produce glucosamines. These amino sugars participate in synthesis of immune modulatory compounds as well as in glycosylation cascades. In this study, we describe the molecular analyses of Glucosamine-6 phosphate-N-acetyl Transferase (GNPNAT1), a key enzyme that converts D-glucosamine 6-phosphate to N-acetyl-D-glucosamine 6-phosphate, in prostate cancer. Our results indicate upregulation of GNPNAT1 in organ-confined prostate cancer as compared to benign adjacent tissue as well as metastatic tissue and regulation of the pathway by androgen. Stable knockdown of GNPNAT1 in androgen dependent LNCap cells leads to diminished cell growth and cell cycle arrest. In contrast, growth and cell cycle are not affected by the knockdown of GNPNAT1 in androgen independent C4-2 cells. Knockdown of GNPNAT1 in C4-2 cells enhances invasiveness which is not observed in LNCap knockdown cells. In this work we show that GNPNAT1 is linked to androgen receptor (AR) action and thus is a critical enzyme for the survival of androgen dependent prostate cancer cells. Citation Format: Katrin Panzitt, Ali Shojaie, Nagireddy Putluri, Sumanta Basu, Vasanta Putluri, Susmita Samanta, Michael Ittmann, Ismael Vergara, George Michailidis, Ganesh Palapattu, Arun Sreekumar. Integrative analysis of transcriptomic and metabolomic data reveals a critical role for aminosugar metabolism in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5387. doi:10.1158/1538-7445.AM2013-5387
Atherosclerosis in SLE: a potential role for serum parathormone levels

Objective A link between bone metabolism and cardiovascular (CV) disease has been suggested mainly in the general population. In the current study we explored whether altered bone metabolism influence CV risk in patients with SLE. Methods In 138 consecutive patients with SLE, atherosclerosis was assessed by the presence of plaque and/or arterial wall thickening in carotid/femoral arteries by ultrasound. Bone mineral density (BMD) levels and hip/spinal cord fractures together with classical CV disease and osteoporosis risk factors including serum 25(OH) vitamin D3 and parathormone (PTH) levels were recorded in all patients. Serum osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand were quantitated by commercial ELISA. Statistical analysis included both univariate and multivariate models. Results Abnormal PTH serum concentrations (>65 pg/mL)—but not 25(OH) vitamin D3 serum levels—were identified as a risk factor for both plaque formation and arterial wall thickening in patients with SLE (ORs (95% CIs): 8.2 (1.8 to 37.4) and 3.9 (1.3 to 11.8), respectively). This association remained significant following adjustment for vitamin D3 levels and classical CV risk factors. Moreover, an independent association between osteoporosis with plaque formation and arterial wall thickening was detected following adjustment for total steroid dose, premature menopause and disease duration (ORs (95% CIs): 5.3 (1.1 to 26.2) and 3.5 (1.1 to 11.4), respectively). An inverse correlation between femoral neck BMD values and intima–medial thickness scores was also observed (r: −0.42, p=0.008). Conclusions These findings further strengthen the concept of shared pathophysiological mechanisms between atherogenesis and altered bone metabolism in autoimmune populations, revealing heightened PTH levels as a potential marker for atherosclerosis among patients with SLE.
Classification performance of administrative coding data for detection of invasive fungal infection in paediatric cancer patients

Background Invasive fungal infection (IFI) detection requires application of complex case definitions by trained staff. Administrative coding data (ICD-10-AM) may provide a simplified method for IFI surveillance, but accuracy of case ascertainment in children with cancer is unknown. Objective To determine the classification performance of ICD-10-AM codes for detecting IFI using a gold-standard dataset (r-TERIFIC) of confirmed IFIs in paediatric cancer patients at a quaternary referral centre (Royal Children’s Hospital) in Victoria, Australia from 1st April 2004 to 31st December 2013. Methods ICD-10-AM codes denoting IFI in paediatric patients (<18-years) with haematologic or solid tumour malignancies were extracted from the Victorian Admitted Episodes Dataset and linked to the r-TERIFIC dataset. Sensitivity, positive predictive value (PPV) and the F1 scores of the ICD-10-AM codes were calculated. Results Of 1,671 evaluable patients, 113 (6.76%) had confirmed IFI diagnoses according to gold-standard criteria, while 114 (6.82%) cases were identified using the codes. Of the clinical IFI cases, 68 were in receipt of ≥1 ICD-10-AM code(s) for IFI, corresponding to an overall sensitivity, PPV and F1 score of 60%, respectively. Sensitivity was highest for proven IFI (77% [95% CI: 58–90]; F1 = 47%) and invasive candidiasis (83% [95% CI: 61–95]; F1 = 76%) and lowest for other/unspecified IFI (20% [95% CI: 5.05–72%]; F1 = 5.00%). The most frequent misclassification was coding of invasive aspergillosis as invasive candidiasis. Conclusion ICD-10-AM codes demonstrate moderate sensitivity and PPV to detect IFI in children with cancer. However, specific subsets of proven IFI and invasive candidiasis (codes B37.x) are more accurately coded.
En Guard! The Interactions between Adenoviruses and the DNA Damage Response

Virus–host cell interactions include several skirmishes between the virus and its host, and the DNA damage response (DDR) network is one of their important battlegrounds. Although some aspects of the DDR are exploited by adenovirus (Ad) to improve virus replication, especially at the early phase of infection, a large body of evidence demonstrates that Ad devotes many of its proteins, including E1B-55K, E4orf3, E4orf4, E4orf6, and core protein VII, and utilizes varied mechanisms to inhibit the DDR. These findings indicate that the DDR would strongly restrict Ad replication if allowed to function efficiently. Various Ad serotypes inactivate DNA damage sensors, including the Mre11-Rad50-Nbs1 (MRN) complex, DNA-dependent protein kinase (DNA-PK), and Poly (ADP-ribose) polymerase 1 (PARP-1). As a result, these viruses inhibit signaling via DDR transducers, such as the ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) kinases, to downstream effectors. The different Ad serotypes utilize both shared and distinct mechanisms to inhibit various branches of the DDR. The aim of this review is to understand the interactions between Ad proteins and the DDR and to appreciate how these interactions contribute to viral replication.
Evaluation of Plasma Circulating Cell Free DNA Concentration and Integrity in Patients with Prostate Cancer in Jamaica: A Preliminary Study

Background: Cell free circulating DNA (cfcDNA) is a promising diagnostic tool for prostate cancer (PCa). This study aimed to measure the cfcDNA concentration and integrity in PCa patients using quantitative polymerase chain reaction (qPCR) analysis. This study also assessed the correlation between these molecular biomarkers with total prostate-specific antigen (PSA), Gleason score, prostate volume, and age. Methods: Eleven PCa patients and 9 persons with benign prostatic hyperplasia (BPH) were recruited. Blood samples were collected before prostate biopsy and plasma quantified by qPCR amplification of the ALU 115 DNA sequence, with the ratio of ALU 247 to ALU 115 reflecting cfcDNA integrity. Results: There were no significant differences in median, interquartile range (IQR) cfcDNA concentration or cfcDNA integrity between the patients with PCa (47.9 (214.93) ng/mL; 0.61 (0.49)) and persons with BPH (41.5 (55.13) ng/mL, p = 0.382; 0.67 (0.45), p = 0.342). A weakly positive correlation exists between cfcDNA concentration and total PSA (r = 0.200, p = 0.555) but not with age or Gleason score in PCa patients. Conclusion: cfcDNA concentration was relatively nonsignificantly higher in PCa patients in comparison to persons with BPH, whereas cfcDNA integrity was similar in both groups. Though limited in sample size, this study shows that cfcDNA concentration may be a potentially valuable noninvasive biomarker for the diagnosis of PCa.
Clinical characteristics and prevalence of dihydropteroate synthase gene mutations in Pneumocystis jirovecii-infected AIDS patients from low endemic areas of China

Pneumocystis pneumonia (PCP) is an opportunistic and potentially life-threatening infection of AIDS patients caused by the fungus Pneumocystis jirovecii (P. jirovecii). Trimethoprim-sulfamethoxazole (TMP-SMX) is the most commonly used drug combination in the treatment and prophylaxis of PCP. However, with long-term use of this combination, mutations in the dihydropteroate synthase (DHPS) gene of P. jirovecii bring about the development of resistance. Data on the prevalence of P. jirovecii and its DHPS mutants in China, especially in low endemic areas, are still limited. Thus, in the present study, we measured the P. jirovecii infection rate among HIV-positive and AIDS (HIV/AIDS) patients with suspected PCP and investigated the relationship between CD4+ T cell count and PCP occurrence. As well as the polymerase chain reaction (PCR) analysis and sequencing, the restriction fragment length polymorphism (RFLP) method was used to analyze DHPS point mutation in P. jirovecii strains. P. jirovecii was detected in 40.82% of cases. The clinical symptoms and signs of PCP were not typical; with decreasing CD4+ T cell counts, PCP infection in HIV/AIDS patients increased. In only one case (1.67%), the patients’ DHPS gene could not be cut by the Acc I restriction enzyme. Furthermore, mutation at codon 171 was detected in 11 cases and no mutation was found at codon 57. Patients treated with sulfamethoxazole combined with Voriconazole or Caspofungin exhibited favorable results. After treatment, the symptoms of dyspnea were alleviated, and chest computed tomography findings showed the improvement of lung shadows. These indicated that the prevalence of DHPS mutations in P. jirovecii isolates in AIDS-PCP patients in the region was low. Thus, the contribution of gene mutations to treatment failure requires further research.
CHARGE syndrome without colobomas: Ophthalmic findings

To report ophthalmic findings of patients without colobomas, and with a clinical and molecular diagnosis of CHARGE Syndrome. Retrospective study of ophthalmic findings in 67 CHARGE patients—clinically confirmed diagnosis with positive CHD7 mutation—seen in the Ophthalmology department of Cincinnati Children's Hospital Medical Center between January 1, 2008 through September 25, 2018. Criteria for inclusion in this study was absence of any form of a coloboma in either eye. In our cohort, all patients had a positive CHD7 mutation, in addition to a clinical diagnosis. 19.4% (13/67) of CHARGE patients did not have a coloboma in either eye. 69.2% (9/13) had strabismus, 76.9% (10/13) had a refractive error that warranted refractive correction, 23.1% (3/13) had amblyopia, 38.5% (5/13) had nasolacrimal duct obstruction, 30.8% (4/13) had dry eye syndrome and exposure keratopathy, 15.4% (2/13) had ptosis, 15.4% (2/13) had blepharitis, 15.4% (2/13) had Cortical Visual Impairment, 7.7% (1/13) of patients had optic nerve drusen, 7.7% (1/13) had Marcus Gunn Jaw Winking, and 7.7% (1/13) with an eyelid nevus. There are numerous ophthalmic findings in individuals with CHARGE Syndrome without colobomas. No study to date has evaluated the ophthalmic findings in CHD7 positive CHARGE patients without colobomas. These findings need to be assessed and treated to ensure optimal vision in the CHARGE patient population. Absence of coloboma does not rule out a diagnosis of CHARGE syndrome, and if there is a clinical suspicion, clinical confirmation then genetic testing would be warranted.
Two New Species of Triturus from California

M Y interest in the taxonomy of this genus in California was first stimulated in April, 1934, by the discovery that Triturus embryos collected for experimental purposes near Ukiah, Mendocino County, differed strikingly in their development from those of torosus (Rathke), familiar to me from collections near Stanford, and described in accounts by Ritter (1897) and Storer (1925). As a result of subsequent observations and extensive collecting it has been possible to distinguish two new forms, here described as species, of this common western salamander. The present account is limited to a description of the salient features of the life-history necessary to establish these forms as distinct. The bulk of the data concerning the life-histories, development and relationships in nature of the three forms of California Triturus (including torosus) will be presented later.
Pomegranate fruit development and maturation

SummaryThe development of pomegranate fruit was studied under continental (Bet Shean Valley) and moderate maritime (coastal plain) climatic conditions. Fertile flowers were vase-shaped and developed into fruits. Bell-shaped flowers with few egg cells were sterile and did not produce fruits. Gibberellic acid induced the sterile flowers to develop into small fruits; however, these were devoid of juicy seeds. The growth curve of pomegranate fruits from both climatic regions showed a single sigmoid pattern. The seeds accounted for about half of the fruit weight. The edible juicy tissue of the seeds grew continuously from June to October whereas the internal stone tissue stopped growing and hardened by the end of June. Juice, total soluble solids (TSS) and anthocyanin content increased continuously during maturation while acidity decreased. Fruit of cv Mule’s Head ripens early and has a low acid content, whereas fruit of the late-ripening cv Wonderful has high juice contents, TSS, acids and anthocyanins, and i.
The Antihypertensive Effect of Quercetin in Young Spontaneously Hypertensive Rats; Role of Arachidonic Acid Metabolism

Hypertension affects almost 50% of the adult American population. Metabolites of arachidonic acid (AA) in the kidney play an important role in blood pressure regulation. The present study investigates the blood pressure-lowering potential of quercetin (QR), a naturally occurring polyphenol, and examines its correlation to the modulation of AA metabolism. Spontaneously hypertensive rats (SHR) were randomly divided into four groups. Treatment groups were administered QR in drinking water at concentrations of 10, 30, and 60 mg/L. Blood pressure was monitored at seven-day intervals. After a total of seven weeks of treatment, rats were killed and kidney tissues were collected to examine the activity of the two major enzymes involved in AA metabolism in the kidney, namely cytochrome P450 (CYP)4A and soluble epoxide hydrolase (sEH). Medium- and high-dose QR resisted the rise in blood pressure observed in the untreated SHR and significantly inhibited the activity of the CYP4A enzyme in renal cortical microsomes. The activity of the sEH enzyme in renal cortical cytosols was significantly inhibited only by the high QR dose. Our data not only demonstrate the antihypertensive effect of QR, but also provide a novel mechanism for its underlying cardioprotective properties.
The Preputial Organ of Snails in the Genus Helisoma (Gastropoda: Pulmonata)

The structure of the penis of members of the family Planorbidae has be:n considered by several workers. In this family, as well as in other families of the Basommatophora and the Stylommatophora, it has been used as one of the important genital structures in taxonomic studies largely because it reveals many generic and specific relations. In the classical work on the morphology of planorbids by Buchner (1891), the penis of members of the genera Planorbarius, Segmentina, Planorbis and Anisus, Bathyomphalus and Gyrautus were compared. Rao (1923) and also Baker (1933 and 1945) described the penis of Indoplanorbis in considerable detail. Soos (1935) dealt with the genitalia of Hungarian planorbids, particularly Anisus (Tropidiscus), Gyvaulus and Armiger and he, too, emphasized the i:rnportance of the penis in taxonomy. The presence of a "penial gland" in the North American genus Helisoma was first reported by Baker (1926) and he also found it later in several other genera of American, European, and Asiatic planorbids. This same investigator (1931) thought that the gland was in some way involved in the formation of the spermatophore and, consequently, called it the spermatophore gland. Later, Baker realized that this assertion was not in agreement with the structure of this organ. In 1945 he stated that the function of the "penial gland" "is insufficiently known but it seemed to him that the secretion of the gland might serve to dilate an opening through which the verge protrudes or that the gland might serve as an excitatory organ or sarcobelum. In this present study, special attention is given to the morphological and histological structure of the organ, as well as to the mating habits of the snails, in order to clarify how this gland functions. Helisoma trivolvis was used mainly for this work, but a comparison was also made with certain other members of this genus. Further studies on other genera will be published in a forthcoming paper.
Chemopreventive Effect of Dietary Anthocyanins against Gastrointestinal Cancers: A Review of Recent Advances and Perspectives

Anthocyanins are a group of dietary polyphenols, abundant mainly in fruits and their products. Dietary interventions of anthocyanins are being studied extensively related to the prevention of gastrointestinal (GI) cancer, among many other chronic disorders. This review summarizes the hereditary and non-hereditary characteristics of GI cancers, chemistry, and bioavailability of anthocyanins, and the most recent findings of anthocyanin in GI cancer prevention through modulating cellular signaling pathways. GI cancer-preventive attributes of anthocyanins are primarily due to their antioxidative, anti-inflammatory, and anti-proliferative properties, and their ability to regulate gene expression and metabolic pathways, as well as induce the apoptosis of cancer cells.
Thymoquinone and Difluoromethylornithine (DFMO) Synergistically Induce Apoptosis of Human Acute T Lymphoblastic Leukemia Jurkat Cells Through the Modulation of Epigenetic Pathways

Thymoquinone (TQ), a natural anticancer agent exerts cytotoxic effects on several tumors by targeting multiple pathways, including apoptosis. Difluoromethylornithine (DFMO), an irreversible inhibitor of the ornithine decarboxylase (ODC) enzyme, has shown promising inhibitory activities in many cancers including leukemia by decreasing the biosynthesis of the intracellular polyamines. The present study aimed to investigate the combinatorial cytotoxic effects of TQ and DFMO on human acute T lymphoblastic leukemia Jurkat cells and to determine the underlying mechanisms. Here, we show that the combination of DFMO and TQ significantly reduced cell viability and resulted in significant synergistic effects on apoptosis when compared to either DFMO or TQ alone. RNA-sequencing showed that many key epigenetic players including Ubiquitin-like containing PHD and Ring finger 1 (UHRF1) and its 2 partners DNA methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1) were down-regulated in DFMO-treated Jurkat cells. The combination of DFMO and TQ dramatically decreased the expression of UHRF1, DNMT1 and HDAC1 genes compared to either DFMO or TQ alone. UHRF1 knockdown led to a decrease in Jurkat cell viability. In conclusion, these results suggest that the combination of DFMO and TQ could be a promising new strategy for the treatment of human acute T lymphoblastic leukemia by targeting the epigenetic code.