Miracle-dz/UniFAR-FTUs huggingface dataset:
Ex vivo physiological compression of human osteoarthritis cartilage modulates cellular and matrix components

Mechanical stimulation appears to play a key role in cartilage homeostasis maintenance, but it can also contribute to osteoarthritis (OA) pathogenesis. Accumulating evidence suggests that cartilage loading in the physiological range contributes to tissue integrity maintenance, whereas excessive or reduced loading have catabolic effects. However, how mechanical stimuli can regulate joint homeostasis is still not completely elucidated and few data are available on human cartilage. We aimed at investigating human OA cartilage response to ex vivo loading at physiological intensity. Cartilage explants from ten OA patients were subjected to ex vivo controlled compression, then recovered and used for gene and protein expression analysis of cartilage homeostasis markers. Compressed samples were compared to uncompressed ones in presence or without interleukin 1β (IL-1β) or interleukin 4 (IL-4). Cartilage explants compressed in combination with IL-4 treatment showed the best histological scores. Mechanical stimulation was able to significantly modify the expression of collagen type II (collagen 2), aggrecan, SOX9 transcription factor, cartilage oligomeric matrix protein (COMP), collagen degradation marker C2C and vascular endothelial growth factor (VEGF). Conversely, ADAMTS4 metallopeptidase, interleukin 4 receptor alpha (IL4Rα), chondroitin sulfate 846 epitope (CS846), procollagen type 2 C-propeptide (CPII) and glycosaminoglycans (GAG) appeared not modulated. Our data suggest that physiological compression of OA human cartilage modulates the inflammatory milieu by differently affecting the expression of components and homeostasis regulators of the cartilage extracellular matrix.
Regenerative potential of human dental pulp stem cells in the treatment of stress urinary incontinence: In vitro and in vivo study

To evaluate the regenerative potential of human dental pulp stem cells (hDPSCs) in an animal model of stress urinary incontinence (SUI). SUI, an involuntary leakage of urine, is due to physical stress involving an increase in bladder pressure and a damage of external urethral sphincter affecting muscles and nerves. Conventional therapies can only relieve the symptoms. Human DPSCs are characterized by peculiar stemness and immunomodulatory properties and might provide an alternative tool for SUI therapy.
Examining Multilevel Factors Associated with the Process of Resilience among Women Living with HIV in a Large Canadian Cohort Study: A Structural Equation Modeling Approach

Objectives: We examined how multiple, nested, and interacting systems impact the protective process of resilience for women living with HIV (WLWH). Methods: Using data from a Cohort Study, we conducted univariate analyses, multivariable logistic regression, and a 2-step structural equation modeling for the outcome, high resilience (N = 1422). Results: Participants reported high overall resilience scores with a mean of 62.2 (standard deviation = 8.1) and median of 64 (interquartile range = 59-69). The odds of having high resilience were greater for those residing in Quebec compared to Ontario (adjusted odds ratio [aOR] = 2.1 [1.6, 2.9]) and British Columbia (aOR = 1.8 [1.3, 2.5]). Transgender women had increased odds of high resilience than cisgender women (aOR = 1.9 [1.0, 3.6]). There were higher odds of resilience for those without mental health diagnoses (aOR = 2.4 [1.9, 3.0]), non-binge drinkers (aOR=1.5 [1.1, 2.1]), and not currently versus previously injecting drugs (aOR = 3.6 [2.1, 5.9]). Structural equation modeling confirmed that factors influencing resilience lie at multiple levels: micro, meso, exo, and macro systems of influence. Conclusion: There is a need to consider resilience as the interaction between the person and their environments, informing the development of multilevel interventions to support resilience among WLWH.
Transversus abdominis plane block and quadratus lumborum block did not reduce the incidence or severity of chronic postsurgical pain following cesarean section: a prospective, observational study.

BACKGROUND Sparse data exist on the prevalence and severity of chronic postsurgical pain (CPSP) following cesarean section. Our study aimed to compare the effectiveness of transversus abdominis plane (TAP) block and quadratus lumborum block (QLB) in the prevention of CPSP after cesarean section. METHODS The study was conducted at a tertiary hospital from June 2017 to July 2018 as a prospective, observational trial. We recruited 233 women with singleton pregnancies, above 18 years of age, ≥ 36 weeks of gestation, undergoing cesarean section under spinal anesthesia. The patients received either TAP block or QLB as the primary analgesia technique following cesarean section. The control group consisted of patients without any postsurgical plane block. The incidence and characteristics of chronic pain were evaluated using the Neuropathic Pain Symptom Inventory at the first, third, and sixth months after surgery. RESULTS Fewer patients in the control group perceived CPSP than in TAP or QLB groups one and three months after cesarean section, but not after six months. Accordingly, CPSP severity was significantly lower in the control group than after plane blocks at the first and third month. No difference in the risk of CPSP was found between different indications for cesarean delivery. CONCLUSIONS CPSP is highly prevalent following cesarean section. The studied plane blocks did not reduce the incidence or severity of CPSP after cesarean section when compared to the standard analgesic regimen.
Implicit Theories of Child Sexual Exploitation Material Offenders: Cross-Cultural Validation of Interview Findings

Offense-supportive cognitions are thought to result from underlying implicit theories (ITs). As child sexual exploitation material (CSEM) users are a distinct type of sex offender, Bartels and Merdian proposed that CSEM offenders hold five different ITs from those endorsed by contact sex offenders (i.e., Unhappy World, Self as Uncontrollable, Child as Sexual Object, Nature of Harm [CSEM variant], and Self as Collector), linked by an assumption about the Reinforcing Nature of the Internet. This article reports a conceptual content analysis of 23 interviews conducted with CSEM offenders in the United Kingdom and Spain. Support for all CSEM-specific ITs was found across both samples, providing an empirical validation of this conceptualization. Finally, four ITs originally identified for contact sex offenders were also identified, namely, Uncontrollability, Child as Sexual Being, Dangerous World, and Nature of Harm. Further validation of CSEM-related ITs is encouraged.
Decorin Regulates the Aggrecan Network Integrity and Biomechanical Functions of Cartilage Extracellular Matrix.

Joint biomechanical functions rely on the integrity of cartilage extracellular matrix. Understanding the molecular activities that govern cartilage matrix assembly is critical for developing effective cartilage regeneration strategies. This study elucidated the role of decorin, a small leucine rich proteoglycan, in the structure and biomechanical functions of cartilage. In decorin-null cartilage, we discovered a substantial reduction of aggrecan content, the major proteoglycan of cartilage matrix, and mild changes in collagen fibril structure. This loss of aggrecan resulted in significantly impaired biomechanical properties of cartilage, including decreased modulus, elevated hydraulic permeability and reduced energy dissipation capabilities. At the cellular level, we found that decorin functions to increase the retention of aggrecan in the neo-matrix of chondrocytes, rather than to directly influence the biosynthesis of aggrecan. At the molecular level, we demonstrated that decorin significantly increases the adhesion between aggrecan and aggrecan molecules, and between aggrecan molecules and collagen II fibrils. We hypothesize that decorin plays a crucial structural role in mediating the matrix integrity and biomechanical functions of cartilage by providing physical linkages to increase the adhesion and assembly of aggrecan molecules at the nanoscale.
The modality switching costs of Chinese–English bilinguals in the processing of L1 and L2

Modality switching cost indicates that people’s performance becomes worse when they judge sequential information that is related to different sensory modalities than judging information that is related to the same modality. In this study, we conducted three experiments on proficient and non-proficient bilingual individuals to investigate the modality switching costs in L1 and L2 processing separately. In Experiment 1, materials were L1 and L2 words that were either conceptually related to a visual modality (e.g., light) or related to an auditory modality (e.g., song). The modality switching costs were investigated in a lexical decision task in both L1 and L2. Experiment 2 further explored the modality switching costs while weakening the activation level of the perceptual modality by adding a set of fillers. Experiment 3 used a word-naming task to explore the modality switching effect in language production in L1 and L2. Results of these experiments showed that the modality switching costs appeared in both language comprehension and production in L1 and L2 conditions. The magnitude of the modality switching costs was conditionally modulated by the L2 proficiency level, such as in the L2 condition in Experiment 1 and in both L1 and L2 conditions in Experiment 3. These results suggest that sensorimotor simulation is involved in not only language comprehension but also language production. The sensorimotor simulation that is acquired in L1 can be transferred to L2.
Intensive measures of luminescence in GaN/InGaN heterostructures

The intensive measures of luminescence in a GaN/InGaN multiple quantum well system are used to examine the thermodynamics and phenomenological structure. The radiative /nonradiative transitions along with absorbed or emitted phonons that occur between the different quantum states of the electrons and holes associated with these processes make the quantum efficiency of a semiconductor nanosystem in an equilibrium state an extensive property. It has long been recognized that tuning of the indium (In) composition in InGaN interlayers gives the potential to obtain a spectrum in the near-infrared to near-ultraviolet spectral range. The thermodynamic intensive properties, including the Debye temperature, carrier temperature, and junction temperature, are the most appropriate metrics to describe the optical-related interactions inherent in a given heterostructure and so can be used as the state variables for understanding the quantum exchange behaviors. The energetic features of the quantum processes are characterized based on analysis of the intensive parameters as determined by means of electroluminescence (EL) and photoluminescence (PL) spectroscopy and current-voltage measurement and then correlated with the designed InGaN/GaN microstructures. According to the McCumber-Sturge theory, the EL and PL Debye temperatures obtained experimentally signal the strength of the electron-phonon and photon-phonon interaction, respectively, while the EL and PL carrier/junction temperatures correspond to the carrier localization. Higher EL Debye temperatures and lower EL carrier/junction temperatures reflect significantly higher luminescence quantum yields, indicative of electron-phonon coupling in the transfer of thermal energy between the confined electrons and the enhancement by excited phonons of heat-assisted emissions. On the other hand, the observation of low luminescence efficiency, corresponding to the lower PL Debye temperatures and higher PL carrier/junction temperatures, is attributed to photon-phonon coupling. These findings are in good accordance to the dependence of the EL and PL quantum efficiency on the In-content of the InGaN/GaN barriers, suggesting that the characteristic Debye and carrier/junction temperatures are intensive parameters useful for assessing the optical properties of a nano-engineered semiconductor heterostructure.
The utility of fecal lactoferrin measurements in predicting disease activity of hospitalized patients with ulcerative colitis

Background: Early identification of pediatric patients with Inflammatory Bowel Disease (IBD), including ulcerative colitis and Crohn disease, is important to help clinicians design optimal treatment regimens. Existing endoscopic techniques are effective in identifying disease activity. However, these methods are invasive, expensive, and less amenable to serial measurement. Recent studies have identified potential serologic and fecal biomarkers that may have the potential to provide clinicians with a more objective evaluation of disease activity. In the case of ulcerative colitis (UC), in which disease is confined to the large intestine, the information provided by fecal biomarkers is likely to be more specific than that provided by serologic biomarkers. Fecal lactoferrin (FLA) is one such biomarker that has shown to be useful not only in identifying levels of colonic inflammation, but also for use as a predictor of disease relapse and treatment efficacy. Measurement of fecal lactoferrin, in conjunction with information provided by other diagnostic modalities could expedite patient assessment and treatment. Additionally, it has been suggested that fecal lactoferrin levels may also provide prognostic information about response to treatment and disease outcome in pediatric patients with UC. The goal vii of this study is to explore the relationship between changes in FLA levels and response to medical therapy in hospitalized pediatric patients with UC. Methods: Serial stool samples were collected daily from 10 patients admitted for management of severe active UC. Of these 10 patients, 3 responded favorably to standard treatment with intravenous corticosteroid therapy and were discharged to complete a course of oral steroids. 7 were unresponsive to steroid therapy and went on to require rescue (more intensive) medical therapy. Changes in FLA were correlated with steroid response and medical disposition at the time of discharge. Results: A t-test was performed to determine the significance of the differences in percent change in FLA levels between patients discharged on steroids and patients discharged on rescue therapy. Patients discharged on steroids demonstrated a net decrease in FLA levels over the course of the first three days of steroid treatment while patients ultimately requiring rescue medical therapy demonstrated a net increase in FLA levels (mean values = -64.4% and +203.8%, respectively). A difference was found between the averages; however, this value did not reach statistical significance when analyzed with a t-test (p = 0.18).
Embolism resistance of different aged stems of a California oak species (Quercus douglasii): Optical and microCT methods differ from the benchtop-dehydration standard.

Vulnerability of xylem to embolism is an important trait related to drought resistance of plants. Methods continue to be developed and debated for measuring embolism. We tested three methods (benchtop dehydration/hydraulic, microCT, and optical) for assessing the vulnerability to embolism of a native California oak species (Quercus douglasii), including an analysis of three different stem ages. All three methods were found to significantly differ in their estimates, with a greater resistance to embolism as follows: microCT>optical>hydraulic. Careful testing was conducted for the hydraulic method to evaluate multiple known potential artifacts and none were found. One-year-old stems were more resistant than older stems using microCT and optical methods, but not hydraulic methods. Divergence between the microCT and optical methods from the standard hydraulic method were consistent with predictions based on known errors when estimating theoretical losses in hydraulic function in both microCT and optical methods. When the goal of a study is to describe or predict losses in hydraulic conductivity, neither the microCT nor optical methods are reliable for accurately constructing vulnerability curves of stems; nevertheless, these methods may be useful if the goal of a study is to identify embolism events irrespective of hydraulic conductivity or hydraulic function.
Chondrogenic differentiation of human bone marrow‐derived mesenchymal stromal cells in a three‐dimensional environment

Cell therapy combined with biomaterial scaffolds is used to treat cartilage defects. We hypothesized that chondrogenic differentiation bone marrow‐derived mesenchymal stem cells (BM‐MSCs) in three‐dimensional biomaterial scaffolds would initiate cartilaginous matrix deposition and prepare the construct for cartilage regeneration in situ. The chondrogenic capability of human BM‐MSCs was first verified in a pellet culture. The BM‐MSCs were then either seeded onto a composite scaffold rhCo‐PLA combining polylactide and collagen type II (C2) or type III (C3), or commercial collagen type I/III membrane (CG). The BM‐MSCs were either cultured in a proliferation medium or chondrogenic culture medium. Adult human chondrocytes (ACs) served as controls. After 3, 14, and 28 days, the constructs were analyzed with quantitative polymerase chain reaction and confocal microscopy and sulfated glycosaminoglycans (GAGs) were measured. The differentiated BM‐MSCs entered a hypertrophic state by Day 14 of culture. The ACs showed dedifferentiation with no expression of chondrogenic genes and low amount of GAG. The CG membrane induced the highest expression levels of hypertrophic genes. The two different collagen types in composite scaffolds yielded similar results. Regardless of the biomaterial scaffold, culturing BM‐MSCs in chondrogenic differentiation medium resulted in chondrocyte hypertrophy. Thus, caution for cell fate is required when designing cell‐biomaterial constructs for cartilage regeneration.
Diminished S-adenosylmethionine biosynthesis and its metabolism in a model of hepatocellular carcinoma is recuperated by an adenosine derivative

ABSTRACT S-adenosylmethionine (SAM), biosynthesis from methionine and ATP, is markedly decreased in hepatocellularular carcinoma (HCC) for a diminution in ATP levels, and the down regulation of the liver specific MAT1a enzyme. Its metabolic activity is very important in the transmethylation reactions, the methionine cycle, the biosynthesis of glutathione (GSH) and the polyamine pathway, which are markedly affected in the HCC. The chemo-preventive effect of IFC305 in HCC induced by DEN, and the increase of ATP and SAM in CCl4-induced cirrhosis have been previously demonstrated. The aim of this work was to test whether this chemo-preventive effect is mediated by the induction of SAM biosynthesis and its metabolic flow. SAM hepatic levels and the methionine cycle were recovered with IFC305 treatment, restoring transmethylation and transsulfuration activities. IFC305 treatment, increased MAT1a levels and decrease MAT2a levels through modulation of their post-transcriptional regulation. This occurred through the binding of the AUF1 (binding factor 1 AU-rich sites) and HuR (human antigen R) ribonucleoproteins to Mat1a and Mat2a messenger RNAs, which maintained their nuclear localization. Finally, the compound inhibited the polyamine pathway favoring the recuperation of the normal methionine and one carbon cycle recuperating the metabolic flow of methionine, which probably facilitated its HCC chemo-preventive effect.
An Attempt to Identify Reproducible High-Density EEG Markers of PTSD during Sleep.

STUDY OBJECTIVES We examined electroencephalogram (EEG) spectral power to study abnormalities in regional brain activity in post-traumatic stress disorder (PTSD) during sleep. We aimed to identify sleep EEG markers of PTSD that were reproducible across nights and subsamples of our study population. METHODS Seventy-eight combat-exposed veteran men with (n = 31) and without (n = 47) PTSD completed two consecutive nights of high-density EEG recordings in a laboratory. We performed spectral-topographical EEG analyses on data from both nights. To assess reproducibility, we used the first 47 consecutive participants (18 with PTSD) for initial discovery and the remaining 31 participants (13 with PTSD) for replication. RESULTS In the discovery analysis, compared to non-PTSD participants, PTSD participants exhibited 1) reduced delta power (1-4 Hz) in the centro-parietal regions during non-rapid-eye-movement (NREM) sleep and 2) elevated high-frequency power, most prominent in the gamma band (30-40 Hz), in the antero-frontal regions during both NREM and rapid-eye-movement (REM) sleep. These findings were consistent across the two study nights, with reproducible trends in the replication analysis. We found no significant group differences in theta power (4-8 Hz) during REM sleep and sigma power (12-15 Hz) during N2 sleep. CONCLUSIONS The reduced centro-parietal NREM delta power, indicating reduced sleep depth, and the elevated antero-frontal NREM and REM gamma powers, indicating heightened central arousal, are potential objective sleep markers of PTSD. If independently validated, these putative EEG markers may offer new targets for the development of sleep-specific PTSD diagnostics and interventions.
Pharmacotherapeutic options for biliary tract cancer: current standard of care and new perspectives

ABSTRACT Introduction: Biliary tract cancer (BTC), which comprises gallbladder cancer, ampullary cancer, and cholangiocarcinoma, is a rare and heterogeneous entity, with limited approved therapeutic options. However, interest in this disease has grown exponentially in recent years, as a mounting body of evidence has shed light on the complex molecular and microenvironmental background of BTC, and clinical investigations have explored a variety of new agents and combinations, with promising results. Areas covered: This review describes the standard of care in advanced BTC and summarizes the most recent evidence available on the pharmacological treatment of resected and advanced disease, focusing on chemotherapy, targeted therapy, and immunotherapy. Expert opinion: The therapeutic armamentarium of BTC has made radical progress after almost a decade of very few positive results. Phase-III evidence now supports the use of adjuvant capecitabine after resection of localized disease, while investigations into improved regimens in the advanced setting are underway, exploring alternative options to the standard gemcitabine-cisplatin doublet. The first positive phase-III trial supports the use of the mFOLFOX6 regimen as a second-line chemotherapy. Targeted therapy against specific genomic alterations can combine with chemotherapy in specific subsets of patients. Despite recent advancements, conducting clinical trials for BTC is still a real challenge.