G2S: A New Deep Learning Tool for Predicting Stool Microbiome Structure From Oral Microbiome Data

Deep learning methodologies have revolutionized prediction in many fields and show the potential to do the same in microbial metagenomics. However, deep learning is still unexplored in the field of microbiology, with only a few software designed to work with microbiome data. Within the meta-community theory, we foresee new perspectives for the development and application of deep learning algorithms in the field of the human microbiome. In this context, we developed G2S, a bioinformatic tool for taxonomic prediction of the human fecal microbiome directly from the oral microbiome data of the same individual. The tool uses a deep convolutional neural network trained on paired oral and fecal samples from populations across the globe, which allows inferring the stool microbiome at the family level more accurately than other available approaches. The tool can be used in retrospective studies, where fecal sampling was not performed, and especially in the field of paleomicrobiology, as a unique opportunity to recover data related to ancient gut microbiome configurations. G2S was validated on already characterized oral and fecal sample pairs, and then applied to ancient microbiome data from dental calculi, to derive putative intestinal components in medieval subjects

Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on IR in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity. Sixty nine NAFLD patients were randomized to 16 weeks exercise supervision (n=38) or counselling (n=31) without dietary modification. All participants underwent MRI/spectroscopy to assess changes in body fat and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset (n=12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean [95% confidence interval (CI)]. Fifty participants (30 exercise, 20 counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29, 35) with baseline liver fat/water % of 18.8% (IQR 10.7, 34.6) completed the study (12/12 exercise and 7/12 counselling completed the clamp studies). Supervised exercise mediated a greater reduction in liver fat/water percentage than counselling [Δ mean change 4.7% (0.01, 9.4); P<0.05], which correlated with the change in cardiorespiratory fitness (r=-0.34, P=0.0173). With exercise, peripheral insulin sensitivity significantly increased (following high-dose insulin) despite no significant change in hepatic glucose production (HGP; following low-dose insulin); no changes were observed in the control group. Although supervised exercise effectively reduced liver fat, improving peripheral IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR

Globigerinoides rublobatus – a new species of Pleistocene planktonic foraminifera

We describe Globigerinoides rublobatus n. sp., a new morphospecies of fossil planktonic foraminifera, from the Pleistocene sediments (∼810 ka) of the Indian Ocean and Pacific Ocean. We use image analysis and morphometry of 860 specimens from International Ocean Discovery Program Site U1483 in the tropical Indian Ocean to document morphological variability in the new morphospecies and related taxa, and we also report it from Pacific Ocean Site U1486 for the first time. The new morphospecies combines characteristics typical of Globigerinoides conglobatus (Brady, 1879) and Globigerinoides ruber (d'Orbigny, 1839), with which it co-occurs, but is distinct from both. Morphometric data indicate that G. rublobatus n. sp. is closer to G. conglobatus, potentially signalling an evolutionary affinity. We find that Globigerinoides rublobatus n. sp. occurs as two variants, a pigmented (pink) form and a non-pigmented (white) form. The non-pigmented forms are on average ∼50 % larger than the pigmented forms. This is so far only the third instance of fossil planktonic foraminifera known to exhibit this pink pigmentation. We regard the pink and white forms as variants of a single morphospecies and suggest the pink form may represent a later evolutionary adaptation

Bridging the extant and fossil record of planktonic foraminifera: implications for the Globigerina lineage

We conducted a morphometric study and wall texture analysis on extant and fossil specimens of the planktonic foraminifera Globigerina falconensis plexus. Our global data reveal morphological inconsistencies between fossil and extant populations. Our results are significant as G. falconensis is widely used in palaeoceanographic studies in conjunction with its sister taxon G. bulloides. Morphologically these two species are similar, with the main difference being the distinctive apertural lip present in G. falconensis. We selected cores covering the entire stratigraphic range of G. falconensis, from the early Miocene to current day, spanning sites from high latitudes in the North Atlantic Ocean and the southern Indian Ocean to sites in equatorial regions. The morphology found in the modern ocean is not consistent with the Miocene holotype of Globigerina falconensis Blow described from lower Miocene sediments in Venezuela. A more lobate morphology evolved in the late Miocene, thus, a new name is required for this morphotype, coexisting in the modern oceans with G. falconensis s.s. We thus describe the new morphospecies, G. neofalconensis for the more lobate forms which evolved in the late Miocene and inhabit the modern oceans. Additionally, we report a pseudocancellate wall texture present in the G. falconensis plexus. We use the molecular sequences from the PR2 database to explore the generic attribution of the G. falconensis lineage, confirming its close relationship with G. bulloides and its retention in the genus Globigerina

Rediscovering Globigerina bollii Cita and Premoli Silva 1960

Globigerina bollii Cita and Premoli Silva was described from the historical Langhian-type section in Langhe, Piedmont (Italy). Due to its peculiar compact morphology, it was set apart from all the other globigerinids typical of the coeval Mediterranean fauna, and it was only reported for a short and limited stratigraphic range. The taxon became a first-order marker for the local biostratigraphy with its own Globigerina bollii Zone within the Langhian stage. However, the species was later synonymised with Globigerina falconensis Blow, ending its use in biostratigraphic schemes, and it was no longer utilised by authors working in the Mediterranean area and Paratethys. We present a reassessment of Globigerina bollii, showing for the first time a full collection of high-quality scanning electron and optical microscope images of the type series of specimens and a comparative study with Mediterranean individuals from the Langhian of the Cretaccio Section (Italy) and extra-Mediterranean individuals from Ocean Drilling Program Site 747 in the Kerguelen Plateau (Indian Ocean). The stratigraphic ranges of all the occurrences cited in the scientific literature from 1960 to the present day and all the references including images of the taxon are compiled. We compare G. bollii to other four-chambered morphospecies inhabiting the oceans during the Miocene, providing a detailed discussion of their morphological differences, which allows us to retain G. bollii as a valid taxon and to disclaim its synonymy with Globigerina falconensis. Our taxonomical observations also allow us to reassign Globigerina bollii to the genus Globoturborotalita, due to its strong affinities with other members of that genus, such as G. eolabiacrassata Spezzaferri and Coxall, and G. ouachitaensis (Howe and Wallace). We present a direct visual comparison with the other representatives of middle Miocene globoturborotaliids. An additional comparison is also discussed with Globigerina bollii lentiana Rögl, a species endemic in the Paratethys. We conclude that the presence of G. bollii in the Mediterranean Basin during such a confined stratigraphic interval (Mediterranean Subzone MMi4c–MMi4d), might be a palaeogeographical indicator of the intermittent opening of the eastern gateway with the Paratethys, affecting the Mediterranean faunas during the Langhian and their migration from oceanic realms into the Paratethys and Mediterranean

Correlation between Quality of Life and severity of Parkinson's Disease by assessing an optimal cut-off point on the Parkinson's Disease questionnaire (PDQ-39) as related to the Hoehn & Yahr (H&Y) scale

Purpose: Strong evidence shows that symptoms in individuals with Parkinson's Disease (PD) restrict both their independence and social participation, leading to a low Quality of Life (QoL). Conversely, a reduced QoL has a negative impact on symptoms. The aim is to evaluate the correlation between QoL and severity of PD by assessing the presence of an optimal cut-off point on the Parkinson's disease questionnaire (PDQ-39) as related to the Hoehn &amp;Yahr (H&amp;Y) scale in a cohort of Italian adults with PD. Methods: A multicenter, cross-sectional study was performed. This study was conducted on a cohort of consecutive individuals. All participants were evaluated with the PDQ-39, and the severity of PD was recorded according to the H&amp;Y scale by a neurologist. Receiver op-erating characteristic (ROC) curves and coordinates, visually inspected, were used to find cut-off points with optimal sensitivity and specificity. These were in turn used to determine the optimal PDQ-39 cut-off score for identifying disease severity according to H&amp;Y stages. Results: 513 individuals were included in the study. The ROC curve analysis showed that QoL worsened with an increase in disease severity and age. Moreover, QoL was worse in females. Conclusions: The results of this study allowed for the correlation of QoL and disease severity in a cohort of individuals with PD. With this cut-off point, it is now possible to make a determination of QoL of an individual with PD at a certain stage of the disease, in a specific age range, and of a particular gender

Levodopa-Induced Dyskinesia Is Associated with Increased Thyrotropin Releasing Hormone in the Dorsal Striatum of Hemi-Parkinsonian Rats

Background Dyskinesias associated with involuntary movements and painful muscle contractions are a common and severe complication of standard levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine) therapy for Parkinson's disease. Pathologic neuroplasticity leading to hyper-responsive dopamine receptor signaling in the sensorimotor striatum is thought to underlie this currently untreatable condition. Methodology/Principal Findings Quantitative real-time polymerase chain reaction (PCR) was employed to evaluate the molecular changes associated with L-DOPA-induced dyskinesias in Parkinson's disease. With this technique, we determined that thyrotropin releasing hormone (TRH) was greatly increased in the dopamine-depleted striatum of hemi-parkinsonian rats that developed abnormal movements in response to L-DOPA therapy, relative to the levels measured in the contralateral non-dopamine-depleted striatum, and in the striatum of non-dyskinetic control rats. ProTRH immunostaining suggested that TRH peptide levels were almost absent in the dopamine-depleted striatum of control rats that did not develop dyskinesias, but in the dyskinetic rats, proTRH immunostaining was dramatically up-regulated in the striatum, particularly in the sensorimotor striatum. This up-regulation of TRH peptide affected striatal medium spiny neurons of both the direct and indirect pathways, as well as neurons in striosomes. Conclusions/Significance TRH is not known to be a key striatal neuromodulator, but intrastriatal injection of TRH in experimental animals can induce abnormal movements, apparently through increasing dopamine release. Our finding of a dramatic and selective up-regulation of TRH expression in the sensorimotor striatum of dyskinetic rat models suggests a TRH-mediated regulatory mechanism that may underlie the pathologic neuroplasticity driving dopamine hyper-responsivity in Parkinson's disease.Morris K. Udall Center for Excellence in Parkinson’s Research at MGH/MITNational Institutes of Health (U.S.) (NIH NS38372)American Parkinson Disease Association, Inc.University of Alabama at BirminghamMassachusetts General HospitalNational Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (NIDDK/NIH grant R01 DK58148)National Institute of Neurological Disorders and Stroke (U.S.) (R01 NINDS/NIH grant NS045231)Stanley H. and Sheila G. Sydney FundMichael J. Fox Foundation for Parkinson's Researc

Understanding the role of cerebellum in early Parkinson’s disease: a structural and functional MRI study

Increasing evidence suggests that the cerebellum may have a role in the pathophysiology of Parkinson's disease (PD). Hence, the scope of this study was to investigate whether there are structural and functional alterations of the cerebellum and whether they correlate with motor and non-motor symptoms in early PD patients. Seventy-six patients with early PD and thirty-one age and sex-matched healthy subjects (HS) were enrolled and underwent a 3 T magnetic resonance imaging (MRI) protocol. The following MRI analyses were performed: (1) volumes of 5 cerebellar regions of interest (sensorimotor and cognitive cerebellum, dentate, interposed, and fastigial nuclei); (2) microstructural integrity of the cerebellar white matter connections (inferior, middle, and superior cerebellar peduncles); (3) functional connectivity at rest of the 5 regions of interest already described in point 1 with the rest of brain. Compared to controls, early PD patients showed a significant decrease in gray matter volume of the dentate, interposed and fastigial nuclei, bilaterally. They also showed abnormal, bilateral white matter microstructural integrity in all 3 cerebellar peduncles. Functional connectivity of the 5 cerebellar regions of interest with several areas in the midbrain, basal ganglia and cerebral cortex was altered. Finally, there was a positive correlation between abnormal functional connectivity of the fastigial nucleus with the volume of the nucleus itself and a negative correlation with axial symptoms severity. Our results showed that structural and functional alterations of the cerebellum are present in PD patients and these changes contribute to the pathophysiology of PD in the early phase

Levofloxacin Prophylaxis in Pediatric and Young Adult Allogeneic Hematopoietic Stem Cell Transplantation Recipients Does not Prevent Infective Complications and Infections-related Deaths

Background: The prophylactic use of quinolones in the setting of allogeneic hematopoietic stem cell transplantation (allo-HCT) is controversial and solid evidence is missing, particularly in children. Methods: In this single-center retrospective study, we compared outcomes in patients receiving (n = 74) or not receiving (n = 70) levofloxacin (LVX) prophylaxis, assessing overall survival, event-free survival, acute graft-versus-host disease (aGvHD) and bloodstream infection incidence, and infection-related mortality. Gut microbiota composition was analyzed in a subgroup using 16S rRNA sequencing of stool samples collected pre-HCT and at engraftment. Results: We analyzed 144 allo-HCT in 143 patients performed for any indication. No differences were found in the 2 groups regarding main HCT outcomes, namely, cumulative incidence of aGvHD (37.9% vs 43.5%; P =. 733), grade III-IV aGvHD (12.2% vs 8.7%; P =. 469), gut aGVHD (12.2% vs 17.5%; P =. 451), bloodstream infections (25.6% vs 34.1%; P =. 236) and death from bacterial infection (9.5% vs 4.3%; P = 0.179). In patients experiencing bacterial infections, those receiving prophylaxis showed higher incidence of quinolone-resistant strains (P =. 001). On a subgroup of 50 patients, we analyzed the gut microbiota composition, showing a lower abundance of Blautia (P =. 015), Enterococcus (P =. 011), and Actinomyces (P =. 07) at neutrophil engraftment in patients receiving LVX prophylaxis. Conclusions: LVX prophylaxis in the setting of allo-HCT does not prevent infective complications and increases the prevalence of antibiotic-resistant strains

Globigerinoides rublobatus - a new species of Pleistocene planktonic foraminifera

We describe Globigerinoides rublobatus n. sp., a new morphospecies of fossil planktonic foraminifera, from the Pleistocene sediments (∼810 ka) of the Indian Ocean and Pacific Ocean. We use image analysis and morphometry of 860 specimens from International Ocean Discovery Program Site U1483 in the tropical Indian Ocean to document morphological variability in the new morphospecies and related taxa, and we also report it from Pacific Ocean Site U1486 for the first time. The new morphospecies combines characteristics typical of Globigerinoides conglobatus (Brady, 1879) and Globigerinoides ruber (d'Orbigny, 1839), with which it co-occurs, but is distinct from both. Morphometric data indicate that G. rublobatus n. sp. is closer to G. conglobatus, potentially signalling an evolutionary affinity. We find that Globigerinoides rublobatus n. sp. occurs as two variants, a pigmented (pink) form and a non-pigmented (white) form. The non-pigmented forms are on average ∼50 % larger than the pigmented forms. This is so far only the third instance of fossil planktonic foraminifera known to exhibit this pink pigmentation. We regard the pink and white forms as variants of a single morphospecies and suggest the pink form may represent a later evolutionary adaptation