Miracle-dz/UniFAR-FTUs huggingface dataset:
The relationship between the alterations in metabolite levels in the dorsolateral prefrontal cortex and clinical symptoms of patients with first-episode schizophrenia: a one year follow-up study

Background Reduced brain metabolites such as N-acetyl-aspartate (NAA), glutamate (Glx), Choline (Cho) and myo-inositol (MI) have been repeatedly found in first-episode schizophrenia (FES) and suggest neuronal loss or dysfunction. However, the potential relationship between the metabolite level and the clinical symptoms or the recovery of FES remained unclear. Objectives This study aimed to investigate the correlation between the alterations in dorsolateral prefrontal cortex (DLPFC) metabolite levels of patients with first-episode schizophrenia (FES) and the changes in clinical symptoms after one year treatment. Materials and Methods FES patients underwent 1H-MRS scan twice: one time at the baseline and the other one year later, while the healthy group patients underwent only once at the baseline time. The symptom severity of patients was measured by PANSS. Principal Observations An increase in the NAA/Cr level was detected in the left DLPFC of patients with FES. The change in the NAA/Cr level was significantly correlated with the alteration in their PANSS-P score. The Cho/Cr levels on both sides of DLPFC in patients with FES were lower compared with the healthy controls both at the baseline and after the treatment. The NAA/Cr and MI/Cr levels in the right DLPFC were decreased after the treatment. Conclusions (1) the depletion of NAA in left DLPFC might be a state characteristic; (2) the Cho/Cr level might be the potential endophenotype of schizophrenia; (3) the decrease of NAA/Cr and MI/Cr level in right DLPFC might be due to the development of schizophrenia.
Comment on “Shiatsu as an Adjuvant Therapy for Depression in Patients With Alzheimer’s Disease: A Pilot Study”

Recently, there has been increasing interest toward nonpharmacological approaches for dementia and associated clinical manifestations, such as depression, with the common goal to improve health and quality of life of both patients and caregivers. In this scenario, the role of Shiatsu is of clinical and research interest, although to date a definitive recommendation on a systematic use in clinical practice cannot be made. To overcome the heterogeneity of the previous studies, we tested Shiatsu as an add-on treatment for late-life depression in a dedicated community of patients with mild-to-moderate Alzheimer’s disease. We found a significant adjuvant effect of Shiatsu for depression in these patients and hypothesized a neuroendocrine-mediated action on the neural circuits implicated in mood and affect regulation. However, this finding must be considered preliminary and requires confirmation in larger-scale controlled studies, possibly extending the range of outcome measures and including predictors of response. Future investigations should also include an objective assessment of the hypothalamus-pituitary-adrenocortical axis functioning. Nevertheless, starting from this pilot study, we suggest that a customized protocol applied for an adequate period in a controlled sample will represent a non-invasive and feasible advance for promoting patients’ mood and, possibly, slowing cognitive decline.
Advances in the knowledge of the Inocybe mixtilis group (Inocybaceae, Agaricomycetes), through molecular and morphological studies

Inocybe mixtilis constitutes a complex of species characterized by nodulose-angulose spores, absence of cortina and a more or less bulbous marginate stipe that is not darkening when desiccated. In order to elucidate species limits within the I. mixtilis complex, an ITS-RPB2 phylogeny was performed and interpreted using morphological and ecological characters. Six supported clades were obtained in our analyses that correspond to I. mixtilis, I. subtrivialis, and four new species to science: I. ceskae, I. johannis-stanglii, I. nothomixtilis and I. occulta. Species within this complex can be morphologically recognized through a unique combination of morphological characters, such as the spore shape, cystidial length and shape, presence and development of the velipellis and pileus colour and viscidity. Nevertheless, those characters overlap, especially among I. mixtilis, I. ceskae and I. occulta, and intermediate collections are therefore more reliably identified through ITS-sequencing. Two species, I. ceskae and I. occulta are present in both North America and Europe, while the rest are so far only known in Europe, or Europe and Asia (I. mixtilis). All species, except I. johannis-stanglii, seem to be able to establish ectomycorrhizal association both with conifers and angiosperms. Descriptions, colour illustrations and a key to all known species in the I. mixtilis group are provided.
Optimal targeting of BCL-family proteins in head and neck squamous cell carcinoma requires inhibition of both BCL-xL and MCL-1

Mechanisms of treatment resistance in head and neck squamous cell carcinoma (HNSCC) are not well characterized. In this study, HNSCC tumors from a cohort of prospectively enrolled subjects on an ongoing tissue banking study were divided into those that persisted or recurred locoregionally (n=23) and those that responded without recurrence (n=35). Gene expression was evaluated using llumina HumanHT-12-v3 Expression BeadChip microarrays. Sparse Partial Least Squares – Discriminant Analysis (sPLS-DA) identified 135 genes discriminating treatment-resistant from treatment-sensitive tumors. BCL-xL was identified among 23% of canonical pathways derived from this set of genes using Ingenuity Pathway analysis. The BCL-xL protein was expressed in 8 HNSCC cell lines examined. Cells were treated with the BCL-xL inhibitor, ABT-263 (navitoclax): the average half maximal inhibitory concentration (IC50) was 8. 9μM (range 6.6μM – 13.9μM). Combining ABT-263 did not significantly increase responses to 2 Gy radiation or cisplatin in the majority of cell lines. MCL-1, a potential mediator of resistance to ABT-263, was expressed in all cell lines and HNSCC patient tumors, in addition to BCL-xL. Treatment with the MCL-1 inhibitor, A-1210477, in HNSCC cell lines showed an average IC50 of 10. 7μM (range, 8.8μM to 12.7μM). Adding A-1210477 to ABT-263 (navitoclax) treatment resulted in an average 7-fold reduction in the required lethal dose of ABT-263 (navitoclax) when measured across all 8 cell lines. Synergistic activity was confirmed in PCI15B, Detroit 562, MDA686LN, and HN30 based on Bliss Independence analysis. This study demonstrates that targeting both BCL-xL and MCL-1 is required to optimally inhibit BCL-family pro-survival molecules in HNSCC, and co-inhibition is synergistic in HNSCC cancer cells.
Prognostic factors in IUI

Dear Editor, Prognostic factors in IUI analyses is a subject both topical and of importance if pregnancy rates in IUI are to be improved. Although the recent retrospective study (Sicchieri et al., 2018) aims to decipher the various contributors to IUI pregnancy rates, such as patient age, cause of infertility, ovulation induction method, number of mature follicles and sperm with progressive motility, the overall pregnancy rate of 7.59%/cycle was disappointing and this may give a wrong perception of IUI practice. The UK IUI pregnancy rates averaged around 13.5%/cycle and some clinics exceeding 20%/cycle. It also means that with every 100 women seeking first line treatment as IUI, 25-35% of the cohort will become pregnant (Bahadur et al., 2016a). We even demonstrated how it was possible to overcome the severe oligozoospermic effect by utilising a consecutive ejaculate (Bahadur et al., 2016b). Crucial to IUI success was to switch over to gonadotropin stimulated cycles, aiming for 2-3 follicles, but with a strict cancellation policy to protect the patient from OHSS and multiple births. In more complex and older patients, combination stimulation regimes can be tried. The cost-effective data clearly shows that more pregnancies can occur with gonadotropin stimulated cycles (Peeraer et al., 2018), or where greater than 3 million motile progressive sperm are inseminated. Newer, well-constructed RCT's provide further strong support for using IUI as first treatment option based on high-quality evidence (Bensdorp et al., 2015; Farquhar et al., 2018; Nandi et al., 2017). Sicchieri et al. (2018) rightly draw attention to affordability issues in most parts of the world, and we now know that over 50% of women undergoing IVF do not need IVF (Malchau et al., 2017). The way forward is to achieve IUI pregnancies earlier, paying attention to numerous prognostic factors and tailoring the stimulation method for IUI. In particular, these are associated with the use of gonadotrophin stimulation, having greater than 3 million motile progressive sperm in the insemination, having 2-3 follicles, and above all ensuring safe practice against OHSS and multiple births with a strict cancellation policy in place. Secondly, clinics should monitor their outcomes in real time using a dedicated database. Our proposals should help steer the global use of IUI towards a more effective and efficient first line treatment option.
Effect of Cigarette Smoking on Patient-Reported Outcomes in Hip Arthroscopic Surgery: A Matched-Pair Controlled Study With a Minimum 2-Year Follow-up

Background: The rate of hip arthroscopic surgery has recently increased; however, there is limited literature examining patient-reported outcomes (PROs) in cigarette smokers. Purpose/Hypothesis: The purpose of this study was to evaluate whether smoking status for patients undergoing hip arthroscopic surgery affects clinical findings and PRO scores. We hypothesized that patients who smoke and undergo primary hip arthroscopic surgery will have similar clinical examination findings and preoperative and postoperative PRO scores compared with nonsmoking patients. Study Design: Cohort study; Level of evidence, 3. Methods: Data were collected on all patients who underwent primary hip arthroscopic surgery from February 2008 to July 2015. A retrospective analysis of the data was then conducted to identify patients who reported cigarette use at the time of the index procedure. Patients were matched 1:2 (smoking:nonsmoking) based on sex, age within 5 years, labral treatment (repair vs reconstruction vs debridement), workers’ compensation status, and body mass index within 5 kg/m2. All patients were assessed preoperatively and postoperatively using 4 PRO measures: the modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), Hip Outcome Score–Sport-Specific Subscale (HOS-SSS), and International Hip Outcome Tool–12 (iHOT-12). Pain was estimated using a visual analog scale. Satisfaction was measured on a scale from 0 to 10. Significance was set at P < . 05. Results: A total of 75 hips were included in the smoking group, and 150 hips were included in the control group. Preoperatively, the smoking group had significantly lower PRO scores compared with the control group for the mHHS, NAHS, and HOS-SSS. Both groups demonstrated significant improvement from preoperative levels. A minimum 2-year follow-up was achieved, with a mean of 42.5 months for the smoking group and 47.6 months for the control group (P = .07). At the latest follow-up, the smoking group reported inferior results for all outcome measures compared with controls. The improvement in PRO scores and rates of treatment failure, revision arthroscopic surgery, and complications was not statistically different between the groups. Conclusion: Patients who smoke had lower PRO scores preoperatively and at the latest follow-up compared with nonsmokers. Both groups demonstrated significant improvement in all PRO scores. These results show that while hip arthroscopic surgery may still yield clinical benefit in smokers, these patients may ultimately achieve an inferior functional status. To optimize results, physicians should advise patients to cease smoking before undergoing hip arthroscopic surgery.
Impact of automated OCT in a high-volume eye urgent care setting

Background/Aims Optical coherence tomography (OCT) has become standard of care in the diagnosis and management of a myriad of retinal and optic nerve pathology. Access to diagnostic equipment and skilled imaging personnel in the after-hours setting is often limited. We examined the utility and diagnostic indications for automated OCT in a high-volume after-hours clinic within an eye institute. Methods OCT images obtained over a period of 15 months were reviewed in the context of electronic patient records. Residents and fellows were surveyed regarding their experience with the OCT and its value in emergency patient management. Results 202 patients and 359 eyes were examined. Complaints prompting imaging included flashes/floaters, metamorphopsia, decreased vision and scotomas. Diagnoses included vascular occlusion, retinal detachment, macular hole, cystoid macular oedema and central serous retinopathy. Of the 25 residents and fellows surveyed, most agreed that the OCT that facilitated delivery of optimal urgent management. OCT also aided in the triage of patients to specialty clinics. Conclusion Expanded access to automated OCT in the urgent care setting shows promise for improving the accuracy and timeliness of diagnosis, which can be critical for optimising patient outcomes. OCT also provides clear, immediate documentation of pathology for substantiating medical decision-making.
Molecular and topological reorganizations in mitochondrial architecture interplay during Bax-mediated steps of apoptosis

During apoptosis, Bcl-2 proteins such as Bax and Bak mediate the release of pro-apoptotic proteins from the mitochondria by clustering on the outer mitochondrial membrane and thereby permeabilizing it. However, it remains unclear how outer membrane openings form. Here, we combined different correlative microscopy and electron cryo-tomography approaches to visualize the effects of Bax activity on mitochondria in human cells. Our data show that Bax clusters localize near outer membrane ruptures of highly variable size. Bax clusters contain structural elements suggesting a higher-order organization of their components. Furthermore, unfolding of inner membrane cristae is coupled to changes in the supramolecular assembly of ATP synthases, particularly pronounced at membrane segments exposed to the cytosol by ruptures. Based on our results, we propose a comprehensive model in which molecular reorganizations of the inner membrane and sequestration of outer membrane components into Bax clusters interplay in the formation of outer membrane ruptures.
Cost-Effectiveness of Pharmacological Treatments for Osteoporosis Consistent with the Revised Economic Evaluation Guidelines for Canada

Introduction. Given the lack of independent analyses comparing numerous pharmacotherapies for osteoporosis, the study objective was to identify the optimal osteoporosis treatment based on a woman’s age, fracture history, and ability to tolerate oral bisphosphonates adopting practices recommended in the recently revised Canadian guidelines. Methods. A cost utility analysis from the health care system perspective compared alendronate, etidronate, risedronate, zoledronate, denosumab, and no pharmacotherapy using a Markov model incorporating data on fracture risk and their associated costs, mortality, and disutility and treatment effect. Stratified analysis was conducted based on age, fracture history, and ability to tolerate oral bisphosphonates. Expected lifetime outcomes were obtained through probabilistic analysis with scenario analyses addressing methodological and structural uncertainty. Results. For women able to tolerate oral bisphosphonates, risedronate and etidronate were dominated. Compared to no therapy, alendronate was either dominant or was associated with a low incremental cost per QALY (quality-adjusted life years) gained (ICER)—less than CAN$3,751 based on age and fracture history. In comparison with alendronate, both zoledronate and denosumab were either dominated or associated with a high ICER—greater than CAN$660,000 per QALY. For women unable to tolerate bisphosphonates, dependent on age and fracture history, the ICER for zoledronate versus no therapy ranged from CAN$17,770 to CAN$94,365 per QALY. For all strata, denosumab was dominated by zoledronate or had an ICER greater than CAN$3.0 million. Scenario analyses found consistent findings. Conclusions. Based on a threshold of CAN$50,000 per QALY, alendronate is optimal for osteoporotic women who can tolerate oral bisphosphonates regardless of age or fracture history. For women unable to tolerate oral bisphosphonates, zoledronate is optimal for women with previous fracture or aged 80 to 84 or over 90 with no previous fracture.
Mitochondrial DNA and temperature tolerance in lager yeasts

Mitochondrial genome origin affects the temperature tolerance of synthetic and industrial lager-brewing yeast hybrids. A growing body of research suggests that the mitochondrial genome (mtDNA) is important for temperature adaptation. In the yeast genus Saccharomyces, species have diverged in temperature tolerance, driving their use in high- or low-temperature fermentations. Here, we experimentally test the role of mtDNA in temperature tolerance in synthetic and industrial hybrids (Saccharomyces cerevisiae × Saccharomyces eubayanus or Saccharomyces pastorianus), which cold-brew lager beer. We find that the relative temperature tolerances of hybrids correspond to the parent donating mtDNA, allowing us to modulate lager strain temperature preferences. The strong influence of mitotype on the temperature tolerance of otherwise identical hybrid strains provides support for the mitochondrial climactic adaptation hypothesis in yeasts and demonstrates how mitotype has influenced the world’s most commonly fermented beverage.
Biomaterial-Derived Calcium Carbonate Nanoparticles for Enteric Drug Delivery

Oral drug delivery systems provide the most convenient, noninvasive, readily acceptable alternatives to parenteral systems. In the current work, eggshell-derived calcium carbonate (CaCO3) nanoparticles were used to develop enteric drug delivery system in the form of tablets. CaCO3 nanoparticles were manufactured using top-down ball-milling method and characterized by X-ray diffractometry (XRD) and transmission electron microscopy (TEM) and loaded with 5-fluorouracil as a model drug. Tablets with varying CaCO3 core and binder compositions were fabricated and coated with Eudragit S100 or Eudragit L100. Suitability for enteric delivery of the tablets was tested by oral administration to rabbits and radiography. Radiograph images showed that the tablet remained in the stomach of the rabbit for up to 3 hours. Further modifications of these biomaterial-derived nanoparticles and the coatings will enable manufacturing of stable formulations for slow or controlled release of pharmaceuticals for enteric delivery.
β-Fructofuranosidase and β –D-Fructosyltransferase from New Aspergillus carbonarius PC-4 Strain Isolated from Canned Peach Syrup: Effect of Carbon and Nitrogen Sources on Enzyme Production

β-fructofuranosidase (invertase) and β-D-fructosyltransferase (FTase) are enzymes used in industrial processes to hydrolyze sucrose aiming to produce inverted sugar syrup or fructooligosaccharides. In this work, a black Aspergillus sp. PC-4 was selected among six filamentous fungi isolated from canned peach syrup which were initially screened for invertase production. Cultivations with pure carbon sources showed that invertase and FTase were produced from glucose and sucrose, but high levels were also obtained from raffinose and inulin. Pineapple crown was the best complex carbon source for invertase (6.71 U/mL after 3 days of cultivation) and FTase production (14.60 U/mL after 5 days of cultivation). Yeast extract and ammonium chloride nitrogen sources provided higher production of invertase (6.80 U/mL and 6.30 U/mL, respectively), whereas ammonium nitrate and soybean protein were the best nitrogen sources for FTase production (24.00 U/mL and 24.90 U/mL, respectively). Fermentation parameters for invertase using yeast extract were YP/S = 536.85 U/g and PP = 1.49 U/g/h. FTase production showed values of YP/S = 2,627.93 U/g and PP = 4.4 U/h using soybean protein. The screening for best culture conditions showed an increase of invertase production values by 5.10-fold after 96 h cultivation compared to initial experiments (fungi bioprospection), while FTase production increased by 14.60-fold (44.40 U/mL) after 168 h cultivation. A. carbonarius PC-4 is a new promising strain for invertase and FTase production from low cost carbon sources, whose synthesized enzymes are suitable for the production of inverted sugar, fructose syrups, and fructooligosaccharides.
Ruptured Berry Aneurysms: Clip Or Coil?

Aneurysmal rupture with subarachnoid haemorrhage is a significant cause of morbidity and mortality affecting about 6-12 persons in 100,000 per year. Traditionally, aneurysmal clipping has been employed to manage the condition, but recently endovascular coiling has enjoyed increasing popularity. Here we review these two modalities and assess the possible impact of The International Subarachnoid Aneurysm Trial (ISAT) on their use.
MOLECULAR AND PHYLOGENETIC STUDY OF BACTERIA RESISTANT TO COAL FLY ASH

The assessment of the bacteria in coal fly ash has been a critical issue with respect to its enormous production and utilization purpose. 16S rDNA based fingerprints revealed the resistant bacteria to coal fly ash and the molecular analog was studied. The bacteria observed were Aeromonas punctata, Bacillus cereus, Bacillus probio 32 and Kocuria. The consensus sequences along with the significant alignment of the bacteria were revealed in turn helping in the formulation of their unrooted phylogenetic tree.
An evaluation of tribes and generic relationships in Melioideae (Meliaceae) based on nuclear ITS ribosomal DNA

Phylogenetic analyses of Melioideae, including representatives of all currently recognized tribes, were carried out using nuclear ITS ribosomal DNA sequence data. The secondary structure models employed for ITS1 and ITS2 allowed optimization of the alignment across Meliaceae genera of both subfamilies, yielding a maximum amount of information without the exclusion of some highly variable sites. This study is the first to assess the current circumscription of Melioideae and its tribes in detail, with data independent of morphology. Maximum parsimony, maximum likelihood and Bayesian analyses of nuclear ITS, in contrast to analyses based on plastid rbcL, confirm monophyly for Aglaieae, Sandoriceae and Melieae, an isolated position for Vavaeeae, the position of Pterorhachis and Quivisianthe in Melioideae, and a close relationship between Turraeeae and Trichilieae. Trichilieae are morphologically and genetically the most complex tribe. Trichilieae cannot be separated from Turraeeae, Vavaeeae and Sandoriceae. Anthocarapa and "Pseudocarapa" form a clade but exhibit a high number of autapomorphies, which needs further investigation. We propose to keep Naregamia separate from Turraea, and to reconsider the present circumscription of Trichilieae.