Miracle-dz/UniFAR-FTUs huggingface dataset:
Robot-assisted radical cystectomy with intracorporeal neobladder: impact of learning curve and long-term assessment of functional outcomes.

BACKGROUND There is paucity of data about functional outcomes of Robot-assisted Radical Cystectomy (RARC) with intracorporeal orhotopic neobladder (ICON), and the impact of learning curve (LC) on those outcomes remains to be addressed. We aimed to report long-term functional outcomes of our single center series of RARC with ICON, assessing the role of LC in their achievement. METHODS Patients treated with Robot assisted radical cystectomy with intracorporeal orthotopic neobladder in our center between January 2012 an August 2019 were retrospectively analysed. Preoperative, clinical, perioperative, pathologic and functional data were reported. The first cases were divided in tertiles, for assessing the impact of learning curve on the outcomes evaluated. Long-term functional outcomes of the whole cohort were evaluated. RESULTS Overall, 167 patients were included. Concerning tertiles analysis, operative time (p<0.001), incidence of low (p=0.002) and high grade (p=0.001) complications and hospital stay (p=0.04) decreased significantly over time. Day-time continence recovery probability was significantly lower in the initial case series (1-yr rate 68.4%, 87% and 89.8 for I, II and III tertile, respectively; p=0.04;). Accordingly, Trifecta achievement was significantly higher in II and III tertiles (p=0.01). At a median follow- up of 34 months, the incidence of significant renal function deterioration of the whole cohort was 16.7%. Overall, 12, 24 and 60-mo day-time continence rates were 74.8 %, 82.7 % and 82.7 %. CONCLUSIONS Patients treated at the beginning of the learning curve show worse perioperative and functional results. Once standardized the procedure, complications rates, hospital stay and daytime continence recovery experienced a significant improvement. At a long-term analysis of functional outcomes of our patients, renal function preservation and continence recovery results are encouraging.
Optogenetic inhibition-mediated activity-dependent modification of CA1 pyramidal-interneuron connections during behavior

In vitro work revealed that excitatory synaptic inputs to hippocampal inhibitory interneurons could undergo Hebbian, associative, or non-associative plasticity. Both behavioral and learning-dependent reorganization of these connections has also been demonstrated by measuring spike transmission probabilities in pyramidal cell-interneuron spike cross-correlations that indicate monosynaptic connections. Here we investigated the activity-dependent modification of these connections during exploratory behavior in rats by optogenetically inhibiting pyramidal cell and interneuron subpopulations. Light application and associated firing alteration of pyramidal and interneuron populations led to lasting changes in pyramidal-interneuron connection weights as indicated by spike transmission changes. Spike transmission alterations were predicted by the light-mediated changes in the number of pre- and postsynaptic spike pairing events and by firing rate changes of interneurons but not pyramidal cells. This work demonstrates the presence of activity-dependent associative and non-associative reorganization of pyramidal-interneuron connections triggered by the optogenetic modification of the firing rate and spike synchrony of cells.
Evaluating the traditional bread properties with new formula: Affected by triticale and cress seed gum

During recent years, composite bread is more popular among consumers due to its functional and nutritional properties. Among cereals, triticale has been studied, along with careful observation of its characteristics. In addition, hydrocolloids can be replaced as an appropriate resource due to a decrease in the gluten content. The present study aimed to evaluate the effect of triticale flour replacement at the levels of 0, 100, 150, and 250 g/kg, and cress seed gum at the concentrations of 0, 3, 6, and 10 g/kg on the rheological parameters of dough and physicochemical, textural, microstructural, and sensory properties of bread. Based on the results, formula including composite flour (150 g/kg triticale flour+850 g/kg wheat flour) and cress seed gum at 6 g/kg was the best formulation for improving the texture, color parameters, and general acceptance of both types of bread (Barbari and Lavash). Regarding the Iranian Barbari bread, cress seed gum increased the specific volume, porosity, and brightness, while reduced the hardness compared to the control. Besides, sensory evaluation manifested that 150 g/kg of wheat flour could be replaced with triticale flour for providing a good quality of bread. In conclusion, the addition of 150 g/kg of triticale and 6 g/kg of cress seed gum into composite flour and bread formulations had positive effects on all properties measured in both types of bread.
Suture Tape Augmented Broström Procedure and Early Accelerated Rehabilitation.

BACKGROUND Immediately following a lateral ligament reconstruction of the ankle, the strength of the repair is far less than that of the native anterior talofibular ligament (ATFL). Additionally, early functional rehabilitation has been shown to increase laxity of the repair. We hypothesized that a Broström procedure augmented with a suture-tape construct would allow early functional rehabilitation while maintaining patient reported outcomes within a military population. METHODS This study is a retrospective study of 93 consecutive patients with chronic lateral ankle instability that were treated with a Broström procedure augmented with a suture-tape construct. Subjects were evaluated at 2, 6, and 12 weeks postoperatively, with yearly satisfaction reviews. Demographics and functional outcomes including Foot and Ankle Disability Index (FADI), visual analog scale (VAS), satisfaction score, and clinical measures including single-leg hop and single-leg heel raise were recorded. Our patients included 75 males and 18 females with a mean age of 30 ± 7 (range, 19-51) years; our mean follow-up was 19 (range, 3-48) months. RESULTS The mean FADI score improved from 67 preoperatively to 87 and 90 at 6 and 12 weeks (P < .001), with 60 patients (65%) obtaining a score greater than 90. The mean VAS scores improved from 4.8 preoperatively to 1.4 and 1.3 at 6 and 12 weeks (P < .001). Eighty-two (96%) of the patients asked were able to complete a single-leg hop and single-leg heel raise at 6 weeks. The 12-, 24-, 36-, and 48-month satisfaction scores were 8.5, 9.8, 9.2, and 8.9, respectively. Demographics collected did not impact results. CONCLUSION This study suggests that a Broström procedure augmented with suture tape enabled early safe functional rehabilitation without subsequent failure. Our data also demonstrated a sustained high level of patient satisfaction while preventing reoccurrence within a high-demand military population. LEVEL OF EVIDENCE Level IV, retrospective case series.
Cellular expression of DNA damage/repair and reactive oxygen/nitrogen species in human periodontitis and peri‐implantitis lesions

Abstract Aim of the study To evaluate differences in the cellular expression of DNA damage/repair and reactive oxygen/nitrogen species between human periodontitis and peri‐implantitis lesions. Material and methods 40 patients presenting with generalized severe periodontitis and 40 patients with severe peri‐implantitis were included. Soft tissue biopsies were collected from diseased sites in conjunction with surgical therapy and prepared for histological analysis. Four regions of interest were identified: the pocket epithelium (PE), the infiltrated connective tissue (ICT), which was divided into one inner area facing the PE (ICT‐1) and one outer area (ICT‐2). A non‐infiltrated connective tissue area (NCT) lateral of the ICT was also selected. Results It was demonstrated that the ICT of peri‐implantitis specimens was considerably larger and contained significantly larger area proportions and densities of CD68‐, MPO‐ and iNOS‐positive cells than that of periodontitis samples. Cellular densities were overall higher in the inner ICT zone lateral of the PE (ICT‐1) than in the outer ICT compartment (ICT‐2). While the NCT area lateral of the ICT comprised significantly larger proportions and densities of y‐H2AX‐, iNOS‐, NOX2‐, MPO‐ and PAD4/MPO‐positive cells in peri‐implantitis than in periodontitis sites, a reverse difference was noted for the area proportion and density of 8‐OHdG‐positive cells in the PE. Conclusions It is suggested that peri‐implantitis lesions are associated with an enhanced and upregulated host response and contain larger numbers of neutrophils, macrophages and iNOS‐positive cells than periodontitis lesions.
Characterizing CDK12-Mutated Prostate Cancers

Purpose: Cyclin-dependent kinase 12 (CDK12) aberrations have been reported as a biomarker of response to immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). Herein, we characterize CDK12-mutated mCRPC, presenting clinical, genomic, and tumor-infiltrating lymphocyte (TIL) data. Experimental Design: Patients with mCRPC consented to the molecular analyses of diagnostic and mCRPC biopsies. Genomic analyses involved targeted next-generation (MiSeq; Illumina) and exome sequencing (NovaSeq; Illumina). TILs were assessed by validated immunocytochemistry coupled with deep learning–based artificial intelligence analyses including multiplex immunofluorescence assays for CD4, CD8, and FOXP3 evaluating TIL subsets. The control group comprised a randomly selected mCRPC cohort with sequencing and clinical data available. Results: Biopsies from 913 patients underwent targeted sequencing between February 2015 and October 2019. Forty-three patients (4.7%) had tumors with CDK12 alterations. CDK12-altered cancers had distinctive features, with some revealing high chromosomal break numbers in exome sequencing. Biallelic CDK12-aberrant mCRPCs had shorter overall survival from diagnosis than controls [5.1 years (95% confidence interval (CI), 4.0–7.9) vs. 6.4 years (95% CI, 5.7–7.8); hazard ratio (HR), 1.65 (95% CI, 1.07–2.53); P = 0.02]. Median intratumoral CD3+ cell density was higher in CDK12 cancers, although this was not statistically significant (203.7 vs. 86.7 cells/mm2; P = 0.07). This infiltrate primarily comprised of CD4+FOXP3− cells (50.5 vs. 6.2 cells/mm2; P < 0.0001), where high counts tended to be associated with worse survival from diagnosis (HR, 1.64; 95% CI, 0.95–2.84; P = 0.077) in the overall population. Conclusions: CDK12-altered mCRPCs have worse prognosis, with these tumors surprisingly being primarily enriched for CD4+FOXP3− cells that seem to associate with worse outcome and may be immunosuppressive. See related commentary by Lotan and Antonarakis, p. 380
The prevalence and determinants of vitamin D deficiency in Indonesian infants at birth and six months of age

Background Vitamin D deficiency in infants has been associated with an increased risk of a number of diseases but there are limited data on the prevalence and determinants of vitamin D deficiency from tropical settings with high infant morbidity and mortality. Objective To determine the prevalence and determinants of vitamin D deficiency in infants at birth and at six months of age in Yogyakarta province, Indonesia. Design Serum vitamin D of eligible infants was measured in cord blood at birth and at six months of age. Factors associated with vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) were collected prospectively monthly from birth and concentrations measured by liquid chromatography-tandem mass spectrometry. Independent risk factors were identified by multiple logistic regression. Results Between December 2015 to December 2017, 350 maternal-newborn participants were recruited and followed up. Vitamin D deficiency was detected in 90% (308/344) of cord blood samples and 13% (33/255) of venous blood samples at six months. Longer time outdoors (≥2 hours per day) and maternal multivitamin intake containing vitamin D during pregnancy were protective against vitamin D deficiency at birth (AOR: 0.10, 95% CI: 0.01–0.90 and AOR: 0.21, 95% CI: 0.06–0.68, respectively). Risk factors for vitamin D deficiency at six months included lower cumulative skin-sun exposure score (AOR: 1.12, 95% CI: 1.04–1.20), severe vitamin D deficiency at birth (AOR: 7.73, 95% CI: 1.20–49.60) and exclusive breastfeeding (AOR: 2.64, 95% CI: 1.07–6.49) until six months. Among exclusively breast fed (EBF) infants, a higher skin-sun exposure score was associated with reduced vitamin D deficiency risk. Conclusion In equatorial regions, the role of ‘safe’ morning sun exposure in infants and mothers in populations with medium to dark brown skin pigmentation and effective interventions to prevent vitamin D deficiency in newborns and EBF infants, need further consideration and evaluation.
Diagnosis and treatment of penile injury: ten years experience of an emergency department.

INTRODUCTION To evaluate the imaging accuracy in the diagnosis and clinical management of penile injury. MATERIALS AND METHODS From January 2010 to January 2020, 20 men (median age 40.2 years) were admitted to our Emergency Department with the diagnosis of penile injury; the penile trauma was related to sexual intercourse in 16 cases, masturbation in 3 cases and injury caused by the partner in 1 case. All the patients underwent accurate medical history, clinical examinations and diagnostic imaging. Color Doppler ultrasound (CDU) evaluation was performed by Logiq E9 ecograph (General Electric; Milwaukee, WI) supplied with a linear probe small (7.5-10 MHz); magnetic resonance image (MRI) examination was performed within 3-24 hours from the trauma using a 1.5 Tesla scanner, (ACHIEVA 3T; Philips Healthcare Best, the Netherlands) performing pre-contrast and post-contrast multi-planar turbo spin-echo T1 and T2-weighted sequences. RESULTS 15/20 (75%) men with high suspicion of the tunica albuginea rupture underwent surgical exploration; conversely, 5/20 (25%) patients underwent conservative management. CDU detected 11/15 (73%) fractures of the penis and in 8 of them the length of the rupture was underestimated (more than 5 millimeters). On the contrary, MRI diagnosed all the albuginea ruptures showed by surgical exploration, but underestimated the length of the lesions in 9/15 (60%) cases. The IIEF-5 score administered six months later penile trauma demonstrated a good performance in all the patients. CONCLUSIONS In our series, all the patients with a tunica albuginea rupture < 5 mm. diagnosed by MRI were submitted to conservative management with a complete functional restitutio ad integrum.
Stent-Assisted Coiling of Unruptured MCA Aneurysms Using the LVIS Jr. Device: A Multicenter Registry

Purpose: The low-profile visualized intraluminal support junior (LVIS Jr.) is a new generation low-profile braided stent. Our aim was to evaluate the safety and efficacy of the LVIS Jr. in the stent-assisted coiling of unruptured middle cerebral artery (MCA) aneurysms. This was a multicenter retrospective study. Patient demographics, aneurysm characteristics, procedural details, complications, and the results of clinical and imaging follow-up were analyzed. Four centers participated in the study. A total of 162 consecutive patients with 162 unruptured MCA aneurysms were included for the analysis. The mean aneurysm size was 7.6 mm (range 2 to 37 mm) and 97.5% were wide-necked. Immediate postprocedural angiograms showed Raymond-Roy class 1 in 118 (72.8%), class 2 in 23 (14.2%), and class 3 in 21 patients (13%). Periprocedural complications occurred in 14 patients (8.6%). There were no procedure-related deaths. Follow-up imaging at 12–18 months post-procedure showed Raymond–Roy class 1 in 132 (81.5%), class 2 in 17 (10.5%), and class 3 in 13 patients (8%). There were 3 cases of in-stent stenosis (1.9%). All 162 patients had good clinical outcome (mRS score 0–2) at 90 days post-procedure. Stent-assisted coiling of unruptured MCA aneurysms with the LVIS Jr. stent is safe and effective, with high immediate and long-term total occlusion rates.
Neuroadaptations in the dorsal hippocampus underlie cocaine seeking during prolonged abstinence

Significance Achieving abstinence is difficult for individuals with cocaine use disorder but the greater challenge is avoiding relapse. Relapse vulnerability is provoked by exposure to drug-associated cues that evoke drug craving. Cue-induced drug craving persists during prolonged abstinence and is mediated by neuroadaptations in the brain. We found that activin A is increased in the dorsal hippocampus (DH) during prolonged, but not acute, abstinence and regulates phosphorylation of NMDA receptor subunit GluN2B. Both activin A and GluN2B-containing NMDA receptors in the DH regulate cocaine seeking during prolonged abstinence. Hippocampal synaptic strength is increased during prolonged abstinence and DH projections to lateral septum regulate cocaine seeking. Together, the DH acquires an abstinent-dependent role in regulating cocaine seeking during prolonged abstinence. Relapse vulnerability in substance use disorder is attributed to persistent cue-induced drug seeking that intensifies (or “incubates”) during drug abstinence. Incubated cocaine seeking has been observed in both humans with cocaine use disorder and in preclinical relapse models. This persistent relapse vulnerability is mediated by neuroadaptations in brain regions involved in reward and motivation. The dorsal hippocampus (DH) is involved in context-induced reinstatement of cocaine seeking but the role of the DH in cocaine seeking during prolonged abstinence has not been investigated. Here we found that transforming growth factor-β (TGF-β) superfamily member activin A is increased in the DH on abstinence day (AD) 30 but not AD1 following extended-access cocaine self-administration compared to saline controls. Moreover, activin A does not affect cocaine seeking on AD1 but regulates cocaine seeking on AD30 in a bidirectional manner. Next, we found that activin A regulates phosphorylation of NMDA receptor (NMDAR) subunit GluN2B and that GluN2B-containing NMDARs also regulate expression of cocaine seeking on AD30. Activin A and GluN2B-containing NMDARs have both previously been implicated in hippocampal synaptic plasticity. Therefore, we examined synaptic strength in the DH during prolonged abstinence and observed an increase in moderate long-term potentiation (LTP) in cocaine-treated rats compared to saline controls. Lastly, we examined the role of DH projections to the lateral septum (LS), a brain region implicated in cocaine seeking and found that DH projections to the LS govern cocaine seeking on AD30. Taken together, this study demonstrates a role for the DH in relapse behavior following prolonged abstinence from cocaine self-administration.
Inactivation of TMEM106A promotes lipopolysaccharide‐induced inflammation via the MAPK and NF‐κB signaling pathways in macrophages

Pattern recognition receptors, such as Toll‐like receptors (TLRs), play an important role in the host defense against invading microbial pathogens. Their activation must be precisely regulated, as inappropriate activation or overactivation of TLR signaling pathways may result in inflammatory disorders, such as septic shock or autoimmune diseases. TMEM106A is a type II transmembrane protein constitutively expressed in macrophages. Our current study demonstrated that TMEM106A levels were increased in macrophages upon lipopolysaccharide (LPS) stimulation, as well as in the peripheral monocytes of patients with sepsis. Tmem106a knockout mice were more sensitive to lipopolysaccharide (LPS)‐induced septic shock than wild‐type mice. Further experiments indicated that Tmem106a ablation enhanced the expression of CD80, CD86 and major histocompatibility complex (MHC)‐II in mouse macrophages upon LPS stimulation, accompanied with up‐regulation of tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, interferon (IFN)‐β and inducible nitric oxide synthase (iNOS), indicating the activation of macrophages and polarization towards the M1 inflammatory phenotype. Moreover, elevated mitogen‐activated protein kinase (MAPK) and nuclear factor kappa B (NF‐κB) signaling were found to be involved in the LPS‐induced inflammatory response in Tmem106a−/− macrophages. However, this effect was largely abrogated by macrophage deletion in Tmem106a−/− mice. Therefore, deficiency of Tmem106a in macrophages may enhance the M1 polarization in mice, resulting in inflammation. This suggests that TMEM106A plays an important regulatory role in maintaining macrophage homeostasis.
Alcohol use disorders and associated factors among adults in rural communities in Enugu State, Nigeria: A cross-sectional survey

Abstract Evidence has shown increasing rate of alcohol abuse among rural dwellers. At the same time little is known about the association between alcohol use disorders (AUD) and factors peculiar to this group of people. A cross-sectional study design was adopted to determine the prevalence of AUD and associated factors among adults in rural communities in Enugu State, Nigeria. Multi-stage random sampling technique was used to select 2,996 respondents from six rural communities in Enugu State. Respondents’ demographic, socioeconomic and clinical characteristics were documented. Data on alcohol use disorders were collected using the Alcohol Use Disorder Identification Test (AUDIT). AUDIT cutoff score of ≥ 8 signified presence of AUD. Logistic regression was used to determine the factors associated with the outcome variable, AUD calculating the crude and adjusted odds ratios and their respective confidence intervals (95% CI). The prevalence rates of alcohol use and AUD were 79.7% and 48.1%, respectively. The factors most strongly associated with AUD were eating once per day (OR= 8.59, 95% CI = 4.24–17.40), male gender (OR= 7.50, 95% CI = 6.30–8.93), being an artisan (OR= 5.92, 95% CI = 3.33–10.05), poor knowledge of health effects of alcohol abuse (OR= 4.26, 95% CI = 3.46–5.24), smoking (OR= 4.21, 95% CI = 3.24–5.47), low educational attainment and early age of alcohol initiation. Practicing Christianity, Islamic religion, being single and suffering from diabetes were some of the negative predictors of AUD. Multi-level interventions that encompass the associated factors are recommended to curtail harmful alcohol use in the rural communities.
Relationship between Citizens’ Health Engagement and Intention to Take the COVID-19 Vaccine in Italy: A Mediation Analysis

The actual effectiveness of the still-to-come vaccination against the coronavirus SARS-CoV-2 might be challenged by vaccine hesitancy, a rather common and known phenomenon whose psychological predictors are, nevertheless, still largely debated. Our study aims at understanding how adult citizens’ health engagement, perceived COVID-19 susceptibility and severity, and general vaccine-related attitudes affect the willingness to vaccinate against COVID-19. To that end, on a sample of Italian citizens, we implemented a path model to test the impact of health engagement on the willingness to vaccinate against SARS-CoV-2, and whether this relationship is direct or mediated by the general attitude towards vaccines and the risk perception. Moreover, we tested the configural and weak invariance of the model across gender and three age groups. Results show that health engagement is positively related to the intention to vaccinate and that this relationship is partially mediated by the general attitude towards vaccines. The model appears invariant across genders and partially invariant across age groups, showing some differences in the role of perceived susceptibility. These findings vouch for the implementation of educational campaigns aimed at sustaining future vaccination programs that also include health engagement promotion.