Miracle-dz/UniFAR-FTUs huggingface dataset:
Are all stem cells equal? Systematic review, evidence map, and meta‐analyses of preclinical stem cell‐based therapies for bronchopulmonary dysplasia

Regenerative stem cell‐based therapies for bronchopulmonary dysplasia (BPD), the most common preterm birth complication, demonstrate promise in animals. Failure to objectively appraise available preclinical data and identify knowledge gaps could jeopardize clinical translation. We performed a systematic review and network meta‐analysis (NMA) of preclinical studies testing cell‐based therapies in experimental neonatal lung injury. Fifty‐three studies assessing 15 different cell‐based therapies were identified: 35 studied the effects of mesenchymal stromal cells (MSCs) almost exclusively in hyperoxic rodent models of BPD. Exploratory NMAs, for select outcomes, suggest that MSCs are the most effective therapy. Although a broad range of promising cell‐based therapies has been assessed, few head‐to‐head comparisons and unclear risk of bias exists. Successful clinical translation of cell‐based therapies demands robust preclinical experimental design with appropriately blinded, randomized, and statistically powered studies, based on biological plausibility for a given cell product, in standardized models and endpoints with transparent reporting.
Stable, fragile and recreated – a qualitative study of agency in everyday life with breast and prostate cancer

ABSTRACT Purpose: This study aims to explore how agency is constructed in everyday life with cancer in relation to daily activities and habits. Agency is approached as a key element of daily life existence, and it is constructed in terms of “acting in the world”, self-behaviour, changing routines, identity expectations and life course. Methods: The study is based on a social constructionist approach and the data of 32 participants were gathered through a public call for narratives on “everyday life with breast and prostate cancer” in Finland in 2009. The analysis was conducted by utilizing a discursive research approach and coding. Results: Three categories of agency were identified: stable—where agency continues fluently after cancer; fragile—where the ability to take care of daily activities has deteriorated; and recreated—where living with cancer adapts or creates a new basis for daily living. Conclusions: The findings of the study suggest that everyday life activities and habits define and (de)construct agency, and that these constructions are tightly linked to the ill person’s overall life situation, physical abilities and cultural context. Having cancer can create new challenges to agency in daily life but does not suppress agency.
THE COMPARISON OF TOTAL AND IONISED SERUM CALCIUM LEVEL IN PREECLAMPTIC PREGNANT WOMEN AND THE WOMEN WITH NORMAL PREGNANCY

& ' (! ) * ! " #$% &' ( ) * + $ , -$ . / 0$1 2 3 4 -$ 3*& -)$5 ) ( ) $/ 61/ 7 89 7: ; < #=> 2 3 ) -$ )= 2 3 =? 4 + ' * @ ( < A 1 ; B => ? = A C ) DD C E) F G ( H ) > / )=: D B D =( E / 8 =(=? I J*( 4 F G ;/ C > ; ( KD B L *M> 4 ND 3* & O $ < $M( -$ ) 2 3 ND = *? A &P F G $F $M( -< =( -)$5 ) $> ( ) $/ ) =? $ 5 = $5 7 > 4 , ' * . =( ) M $F =Q 8-)$5 ) / ; F( R S T D T U -$ 3*& -)$5 E / ) 2 3 NN T U T N A &P F G -)$5 E / V A C +) M -)$5 ) F G ;/ ; F( .? R DDD T D V R 4 (< -$ 3*& 2 3 T W T U A &P F G $ ) *M> N T W T L *M> 4V < A 1 -)$5 ) 7 G (= XH ? ) */ 8 * / H Y >$ ,* $Z( 17( A C +) M < -)$ 5 ) ; R DDD T D V 4 -$ 3*& $ * / H Y ; F( 2 3 W T L T KW A &P F G $ ) S T W S T DL -$ 3*& $ */ H Y ; F( ) 2 3 NS T L WN &P F G $ ) A S T D SK T U 4 -$ 3*& $ (= XH ? 2 3 DS T LK T A &P F G $ ) DW T T 4 ; F( 7 3* & -)$5 ; F( $ [ < G -)$5 ) A 1 >$ ,* $/ -$ $ [ ) 2 3 ( H ( -$ 3* )= > 2 3 4 ; \$5 #3* H ] : < C A ( & 4 ., /0.1 * ; P & A 1 ; -$ ) ( ) $/ 2 3 = $F( -=> Y 4 2 / . 3 / ' * -$ ( 8 8 2 3
Immune-Related Adverse Events by Immune Checkpoint Inhibitors Significantly Predict Durable Efficacy Even in Responders with Advanced Non-Small Cell Lung Cancer.

BACKGROUND Although predictive value of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have been suggested by several studies, their assessments were insufficient because patients were categorized only by the occurrence of irAEs. It has not been elucidated whether irAEs also play a significant role even in responders. MATERIALS AND METHODS Between December 2015 and September 2018, 106 patients with advanced non-small cell lung cancer treated with ICIs were enrolled in our prospective biomarker study. Twenty-three of these were responders, defined as those with complete or partial response. We investigated the proportion of irAEs among overall and responders. For responders, progression-free survival (PFS) and overall survival of ICIs were compared between those with and without irAEs. As an exploratory analysis, we measured 41 proteins from peripheral blood before and after ICI treatment. RESULTS The proportion of irAEs was significantly higher in responders than nonresponders (65.2% vs. 19.3%, p < .01). Among responders, clinical characteristics did not differ regardless of the occurrence of irAEs. However, there was a significant difference in PFS among responders (irAE group 19.1 months vs. non-irAE group 5.6 months; hazard ratio: 0.30 [95% confidence interval: 0.10-0.85]; p = .02). Of 41 protein analyses, fibroblast growth factor-2 at baseline and monocyte chemoattractant protein fold change showed significant differences between them (p < .04). CONCLUSION Although this is a small sample-sized study, irAE might be a predictive factor of durable efficacy, even in patients who responded to ICIs. Investigation into the significance of irAEs in responders will contribute to the establishment of optimal administration of ICI. IMPLICATIONS FOR PRACTICE Although the predictive value of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) has been suggested by several studies, it has not been elucidated whether irAEs also play a significant role even in responders. This study showed that more than 60% of responders had irAEs. It demonstrated the strong correlation between irAEs and efficacy even in responders. Investigation into the significance of irAEs in responders will contribute to the establishment of optimal administration of ICI.
Regional variation of human pancreatic islets dimension and its impact on beta cells in Indian population

ABSTRACT Background & objectives: Islet of Langerhans, the endocrine pancreas plays a significant role in glucose metabolism. Obesity and insulin resistance are the major factors responsible for beta cell dysfunction. Asian Indian population has increased susceptibility to diabetes in spite of having lower BMI. The morphology of islets plays a significant role in beta cell function. The present study was designed for better understanding the morphology, composition and distribution of islets in different parts of the pancreas and its impact on beta cell proportion. Methods: We observed islet morphology and beta cell area proportion by Large-scale computer-assisted analysis in 20 adult human pancreases in non-diabetic Indian population. Immunohistochemical staining with anti-synaptophysin and anti-insulin antibody was used to detect islet and beta cells respectively. Whole slide images were analyzed using ImageJ software. Results: Endocrine proportion were heterogeneously increasing from head to tail with maximum islet and beta cell distribution in the tail region. Larger islets were predominately confined to the tail region. The islets in Indian population were relatively smaller in size, but they have more beta cells (20%) when compared to American population. Interpretation & conclusions: The beta cells of larger islets are functionally more active than the smaller islets via paracrine effect. Thus, reduction in the number of larger islets may be one of the probable reasons for increased susceptibility of Indians to diabetes even at lower BMI. Knowledge about the regional distribution of islets will help the surgeons to preserve the islet rich regions during surgery.
The Dichotomous Nature of AZ5104 (an EGFR Inhibitor) Towards RORγ and RORγT

The RORC (RAR related orphan receptor C) gene produces two isoforms by alternative promoter usage: RORγ (nuclear receptor ROR-gamma isoform 1) and RORγT (nuclear receptor ROR-gamma isoform 1). Both proteins have distinct tissue distributions and are involved in several physiological processes, including glucose/lipid metabolism and the development of Th17 lymphocytes. Previously, we developed a stably transfected reporter cell line and used it to screen a library of kinase inhibitors. We found that AZ5104 acts as an RORγ agonist at low micromolar concentrations. Molecular docking analysis showed that this compound occupies the ligand binding domain of the receptor with a significant docking score. However, analysis of the biological activity of this compound in Th17 cells revealed that it downregulates RORγT expression and Th17-related cytokine production via inhibition of SRC-ERK-STAT3 (SRC proto-oncogene - extracellular regulated MAP kinase - signal transducer and activator of transcription 3). We thus identified a compound acting as an agonist of RORγ that, due to the inhibition of downstream elements of EGFR (epidermal growth factor receptor) signaling, exerts different biological activity towards a Th17-specific isoform. Additionally, our results may be relevant in the future for the design of treatments targeting signaling pathways that inhibit Th17-related inflammation in certain autoimmune disorders.
HIV Voluntary Testing among Portuguese Women Attending Family Planning Clinics: Implications for HIV Prevention Education and Testing

ABSTRACT Objectives: The aim of this article is to analyze the factors associated with HIV testing among 767 sexually active women. Methods: Participants were administered several self-report questionnaires that assessed behavioral and psychosocial measures. Results: Overall, 59.8% of the participants reported ever having tested for HIV. Results show that higher levels of education, being pregnant or having been pregnant, concern about AIDS, AIDS knowledge, self-efficacy in condom negotiation and perception of no risk in partner significantly predicted the likelihood of testing among women. Attending the mass was negatively associated with HIV testing. Conclusions: These findings provide information that can be used in the development of a focused gender sensitive HIV prevention program to increase HIV testing.
Empowering Women Researchers in the New Century: IADR’s Strategic Direction

Gender inequality in science, medicine, and dentistry remains a central concern for the biomedical research workforce today. Although progress in areas of inclusivity and gender diversity was reported, growth has been slow. Women still face multiple challenges in reaching higher ranks and leadership positions while maintaining holistic success in these fields. Within dental research and academia, we might observe trends toward a more balanced pipeline. However, women continue to face barriers in seeking leadership roles and achieving economic equity and scholarship recognition. In an effort to evaluate the status of women in dental research and academia, the authors examined the role of the International Association for Dental Research (IADR), a global research organization, which has improved awareness on gender inequality. The goal of this article is to review five crucial issues of gender inequality in oral health research and academics—workforce pipeline, economic inequality, workplace harassment, gender bias in scholarly productivity, and work-life balance—and to discuss proactive steps that the IADR has taken to promote gender equality. Providing networking and training opportunities through effective mentoring and coaching for women researchers, the IADR has developed a robust pipeline of women leaders while promoting gender equality for women in dental academia through a culture shift. As knowledge gaps remained on the levels of conscious and unconscious bias and sexist culture affecting women advancement in academics, as well as the intersectionality of gender with race, gender identity, ability status, sexual orientation, and cultural backgrounds, the IADR has recognized that further research is warranted.
The Effect of Mean Platelet Volume/Platelet Count Ratio on Dipper and Non-Dipper Blood Pressure Status

Background and Objectives: The mean platelet volume (MPV) represents a possible marker of platelet activation. There is an association between the platelet count (PC) and inflammation and platelet reactivity. We assessed the association between the MPV/PC ratio and circadian alterations in blood pressure (BP). Material and Methods: One hundred and twenty subjects in total, 80 hypertensive subjects and 40 healthy subjects (controls), were enrolled in the study group. Twenty four hour ambulatory BP monitoring (ABPM) was applied to all subjects. According to ABPM results, the hypertensive subjects were separated into two groups, such as dippers (n = 40) and non-dippers (n = 40). In all subjects, the collection of venous peripheral blood samples was performed on admission for PC and MPV measurements. Results: The two groups exhibited similar clinical baseline characteristics. A significantly higher MPV/PC ratio was determined in non-dippers compared to that in dippers and normotensives. The higher MPV/PC ratio was observed in non-dippers in comparison with that in dippers and normotensives (0.046 ± 0.007 to 0.032 ± 0.004 fL/[109/L]; 0.046 ± 0.007 to 0.026 ± 0.004 fL/[109/L], p < 0.001, respectively). A receiver operating characteristic (ROC) curve analysis showed that the optimum cut-off value of the MPV/PC ratio for predicting non-dipping patterns in hypertensive patients was 0.036 (area under the curve [AUC]: 0.98, p < 0.001). According to the cut-off value, sensitivity and specificity were found to be 95% and 95%, respectively. Conclusions: The higher MPV/PC ratio was determined in non-dipper hypertensive subjects in comparison with that in dipper hypertensive subjects. An elevation of platelet activity and an increase in thrombus burden are reflected by an increase in the MPV/PC ratio. The MPV/PC ratio may underlie the increase in cardiovascular risk in non-dippers compared to that in dippers.
Determinants of mortality among patients with drug-resistant tuberculosis in northern Nigeria

Background Drug-Resistant tuberculosis (DR-TB) is estimated to cause about 10% of all TB related deaths. There is dearth of data on determinants of DR-TB mortality in Nigeria. Death among DR-TB treated cohorts in Nigeria from 2010 to 2013 was 30%, 29%, 15% and 13% respectively. Our objective was to identify factors affecting survival among DR-TB patients in northern Nigeria. Methods Demographic and clinical data of all DR-TB patients enrolled in Kano, Katsina and Bauchi states of Nigeria between 1st February 2015 and 30th November 2016 was used. Survival analysis was done using Kaplan-Meier and multiple regression with Cox proportional hazard modeling. Results Mean time to death during treatment is 19.2 weeks and 3.9 weeks among those awaiting treatment. Death was recorded among 38 of the 147 DR-TB patients assessed. HIV co-infection significantly increased probability of mortality, with an adjusted hazard ratio (aHR) of 2.35, 95% CI: 1.05–5.29, p = 0.038. Treatment delay showed significant negative association with survival (p = 0.000), not starting treatment significantly reduced probability of survival with an aHR of 7.98, 95% CI: 2.83–22.51, p = 0.000. Adjusted hazard ratios for patients started on treatment more than eight weeks after detection or within two to four weeks after detection, was beneficial though not statistically significant with respective p-values of 0.056 and 0.092. The model of care (facility vs. community-based) did not significantly influence survival. Conclusion Both HIV co-infected DR-TB patients and DR-TB patients that fail to start treatment immediately after diagnosis are at significant risk of mortality. Our study showed no significant difference in mortality based on models of care. The study highlights the need to address programmatic and operational issues pertaining to treatment delays and strengthening DR-TB/HIV co-management as key strategies to reduce mortality.
Polyphenols from Lycium barbarum (Goji) Fruit European Cultivars at Different Maturation Steps: Extraction, HPLC-DAD Analyses, and Biological Evaluation

Goji berries are undoubtedly a source of potentially bioactive compounds but their phytochemical profile can vary depending on their geographical origin, cultivar, and/or industrial processing. A rapid and cheap extraction of the polyphenolic fraction from Lycium barbarum cultivars, applied after homogenization treatments, was combined with high-performance liquid chromatography (HPLC) analyses based on two different methods. The obtained hydroalcoholic extracts, containing interesting secondary metabolites (gallic acid, chlorogenic acid, catechin, sinapinic acid, rutin, and carvacrol), were also submitted to a wide biological screening. The total phenolic and flavonoid contents, the antioxidant capacity using three antioxidant assays, tyrosinase inhibition, and anti-Candida activity were evaluated in order to correlate the impact of the homogenization treatment, geographical origin, and cultivar type on the polyphenolic and flavonoid amount, and consequently the bioactivity. The rutin amount, considered as a quality marker for goji berries according to European Pharmacopeia, varied from ≈200 to ≈400 µg/g among the tested samples, showing important differences observed in relation to the influence of the evaluated parameters.
CD73 Is Enriched in Cutaneous Carcinomas That Invade the Orbit

Purpose: To compare the expression of CD73 in indolent nodular basal cell carcinomas and cutaneous lesions that invade the orbit. Methods: Immunohistochemical staining for CD73 was performed on nodular basal cell carcinomas and invasive basal cell carcinomas. The numbers of positively staining cells were counted across 5 consecutive ×40 microscopic fields, and a statistical comparison was performed via a dedicated computerized software package. Results: Ten control specimens and 11 invasive tumors were analyzed. In nodular basal cell carcinomas, the mean number of positively staining cells was 0.72/×40 field (standard deviation = 0.80 cells/×40 field), whereas invasive tumors demonstrated a mean of 6.53 positive staining cells/×40 field (standard deviation = 3.33 cells/×40 field). This difference was statistically significant (p = 0.0002). Conclusions: CD73 is enriched in orbital invasion of cutaneous carcinomas. This checkpoint may represent an important target for therapeutic management of these lesions. Immunotherapeutic agents that have been designed to treat other neoplasms may decrease the requirement for orbital exenteration in this clinical scenario. CD73 is enriched in orbital invasion of basal cell carcinomas, suggesting that immunomodulation may be an important therapeutic approach to treat this ailment.
Cardiac regeneration and remodelling of the cardiomyocyte cytoarchitecture

Adult mammals are unable to regenerate their hearts after cardiac injury, largely due to the incapacity of cardiomyocytes (CMs) to undergo cell division. However, mammalian embryonic and fetal CMs, similar to CMs from fish and amphibians during their entire life, exhibit robust replicative activity, which stops abruptly after birth and never significantly resumes. Converging evidence indicates that formation of the highly ordered and stable cytoarchitecture of mammalian mature CMs is coupled with loss of their proliferative potential. Here, we review the available information on the role of the cardiac cytoskeleton and sarcomere in the regulation of CM proliferation. The actin cytoskeleton, the intercalated disc, the microtubular network and the dystrophin–glycoprotein complex each sense mechanical cues from the surrounding environment. Furthermore, they participate in the regulation of CM proliferation by impinging on the yes‐associated protein/transcriptional co‐activator with PDZ‐binding motif, β‐catenin and myocardin‐related transcription factor transcriptional co‐activators. Mastering the molecular mechanisms regulating CM proliferation would permit the development of innovative strategies to stimulate cardiac regeneration in adult individuals, a hitherto unachieved yet fundamental therapeutic goal.
Cortisol Levels in Glucagon Stimulation Test in Children Assessed for Short Stature: Clinical and Laboratorial Correlations

Abstract To assess total cortisol levels in children being evaluating for short stature with normal cortisol reserve and to correlate this response to clinical and laboratory data. Children assessed with glucagon test in our department were recruited in this study retrospectively. Inclusion criteria were: i) age>1 year, ii) absence of chronic illness or medication interfering with ACTH-cortisol axis, iii) GH stimulation levels>3ng/mL at least in one provocation test (glucagon or clonidine), iv) absence of multiple pituitary growth hormone deficiencies, v) normal short Synacthen test in cases of low cortisol response in glucagon test.Two hundred and thirty-seven subjects (160 males, 67.5%) with a mean age of 9.02±3.19 years, were finally included in the analysis. Cortisol peak levels but not cortisol AUC were significantly increased in females compared to males (26.83±7.31 μg/dl vs. 24.04±7.20 μg/dl). When linear correlations were studied, both cortisol peak levels and cortisol AUC were linearly but inversely correlated to age (r=−0.234, p<0.001 and r=−0.315, p<0.001, respectively). Finally, cortisol AUC was inversely correlated to weight Z-scores (r=−0.160, p=0.014). When our analysis was limited only to subjects with intact GH response (GH peak> 7 ng/mL), age was still inversely correlated to cortisol AUC (r=−0.312, p<0.001), and cortisol AUC was linearly correlated to GH AUC assessed with clonidine test (r=0.223, p=0.013). Girls, younger and thinner children exhibit higher cortisol response to glucagon test.
Fatal hematologic toxicity with prolonged continuous administration of temozolomide (TMZ) during radiation therapy (RT) in the treatment of newly-diagnosed glioblastoma multiforme (GBM): Report of a Phase II trial

1546 Background: A Phase III trial demonstrated superior survival in GBM patients (pts) treated with postoperative RT and concomitant and adjuvant TMZ. Hematologic toxicity was acceptable; only 7% of pts experienced grade 3/4 toxicity (Stupp et al, ASCO Proc 2004, No. 2). The current phase II trial studied the same regimen. Methods: Pts age ≥ 18 with newly diagnosed histologically-proven GBM and KPS ≥ 60 with normal hematologic, hepatic and renal function were enrolled from 1/2001–10/2002. RT (60 Gy in 30 daily fractions of 2 Gy) and concomitant TMZ 75mg/m2 for up to 42 days were administered. Adjuvant TMZ 200mg/m2 day 1–5 every 28 days for up to 12 cycles was given following RT. Survival and toxicity were primary endpoints. Prophylactic trimethoprim-sulfamethoxazole (TMP-SMZ) 160mg/800mg 3 times weekly was given to those taking dexamethasone. Results: 16 pts were registered and all included in the analysis. The table describes survival and hematologic toxicity of all 16 pts. 3 (3/16, 19%) died from toxic.