Miracle-dz/UniFAR-FTUs huggingface dataset:
Stem Cell Repor ts

Recent studies have demonstrated that human astrocytes and ﬁbroblasts can be directly converted into functional neurons by small molecules. However, ﬁbroblasts, as a potentially better cell resource for transplantation, are not as easy to reprogram as astrocytes regarding their fate to neurons, and chemically induced neurons (iNs) with low efﬁciency from ﬁbroblasts resulted in limited application for the treatment of neurological disorders, including depression. Here, we report that human ﬁbroblasts can be efﬁciently and directly reprog-rammedinto glutamatergic neuron-like cells by seriallyexposing cells to a combination of small molecules.These iNs displayed neuronal transcriptionalnetworks,andalsoexhibitedmatureﬁringpatternsandformedfunctional synapses.Importantly, iNscouldintegrateinto local circuits after transplantation into postnatalmouse brain.Our study providesa rapid andefﬁcient transgene-free approach forchem-ically generating neuron-like cells from human ﬁbroblasts. Furthermore, our approach offers strategies for disease modeling and drug discovery in central nervous system disorders.
Venous ulceration: the pattern of pain and the paradox

Abstract Objectives: this study sought to explore: (a) the personal experiences of patients who were deemed to have venous ulcers and (b) their professional management by nurses and doctors. Design: qualitative, grounded theory study. Participants and setting: 39 patients, 33 nurses and 14 general practitioners in two health districts in England. Findings: the key symptom that led patients to consult with medical practitioners was pain. Due to the lack of medical diagnosis at the condition specific level (‘venous’ or ‘arterial’ ulcer for example), the patients were referred to nurses with the label of ‘leg ulcer’. In order to manage their care, the nurses viewed the wounds and the symptoms described as diagnostic indicators of ulcer type. The patients’ descriptions of pain did not lead to professional management of this symptom. The pattern of pain described has not previously been reported and adds to the knowledge base for this patient group. Conclusions: those caring for these patients need to reflect upon the outcomes of treatment in terms of quality of life as well as wound healing, and adopt approaches that ensure the professional management of pain.
Isoflavone-mediated radioprotection involves regulation of early endothelial cell death and inflammatory signaling in Radiation-Induced lung injury

Abstract Purpose: Vascular damage and inflammation are limiting toxic effects of lung cancer radiotherapy, which lead to pneumonitis and pulmonary fibrosis. We have demonstrated that soy isoflavones (SIF) mitigate these toxic effects at late time points after radiation. However, the process by which SIF impacts the onset of radiation-induced inflammation remains to be elucidated. We have now investigated early events of radiation-induced inflammation and identified cellular and molecular signaling patterns by endothelial cells that could be modified by SIF to control vascular damage and the initiation of lung inflammation. Materials and methods: Histopathological, cellular and molecular studies were performed on mouse lungs from C57Bl/6 mice treated with 10 Gy of thoracic radiation (XRT) in conjunction with daily oral SIF treatment given prior and after radiation. Parallel studies were performed in-vitro using EA.hy926 endothelial cell line with SIF and radiation. Immunohistochemistry, western blots analysis, and flow cytometry were performed on lung tissue or EA.hy926 cells to analyze endothelial cells, their patterns of cell death or survival, and signaling molecules involved in inflammatory events. Results: Histopathological differences in inflammatory infiltrates and vascular injury in lungs, including vascular endothelial cells, were observed with SIF treatment at early time points post-XRT. XRT-induced expression of proinflammatory adhesion molecule ICAM-1 cells was reduced by SIF in-vitro and in-vivo in endothelial cells. Molecular changes in endothelial cells with SIF treatment in conjunction with XRT included increased DNA damage, reduced cell viability and cyclin B1, and inhibition of nuclear translocation of NF-κB. Analysis of cell death showed that SIF treatment promoted apoptotic endothelial cell death and decreased XRT-induced type III cell death. In-vitro molecular studies indicated that SIF + XRT increased apoptotic caspase-9 activation and production of IFNβ while reducing the release of inflammatory HMGB-1 and IL-1α, the cleavage of pyroptotic gasdermin D, and the release of active IL-1β, which are all events associated with type III cell death. Conclusions: SIF + XRT caused changes in patterns of endothelial cell death and survival, proinflammatory molecule release, and adhesion molecule expression at early time points post-XRT associated with early reduction of immune cell recruitment. These findings suggest that SIF could mediate its radioprotective effects in irradiated lungs by limiting excessive immune cell homing via vascular endothelium into damaged lung tissue and curtailing the overall inflammatory response to radiation.
Cell transfer‐based immunotherapies in cancer: A review

In cell transfer therapy (CTT), immune cells such as innate immune‐derived natural killer cells and dendritic cells as well as acquired immune‐related T lymphocytes such as tumor‐infiltrating lymphocytes and cytokine‐activated or genetically modified peripheral blood T cells are used in the management of cancer. These therapies are increasingly becoming the most used treatment modality in cancer after tumor resection, chemotherapy, and radiotherapy. In adoptive cell transfer, the lymphocytes isolated from either a donor or the patient are modified ex vivo and reinfused to target malignant cells. Transferring in vitro‐manipulated immune cells produces a continuous antitumor immune response. In this review, we evaluate the recent advances in CTT for the management of various malignancies.
The mitochondrial deoxyguanosine kinase is required for cancer cell stemness in lung adenocarcinoma

The mitochondrial deoxynucleotide triphosphate (dNTP) is maintained by the mitochondrial deoxynucleoside salvage pathway and dedicated for the mtDNA homeostasis, and the mitochondrial deoxyguanosine kinase (DGUOK) is a rate‐limiting enzyme in this pathway. Here, we investigated the role of the DGUOK in the self‐renewal of lung cancer stem‐like cells (CSC). Our data support that DGUOK overexpression strongly correlates with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis, and CSC self‐renewal. Mechanistically, DGUOK is required for the biogenesis of respiratory complex I and mitochondrial OXPHOS, which in turn regulates CSC self‐renewal through AMPK‐YAP1 signaling. The restoration of mitochondrial OXPHOS in DGUOK KO lung cancer cells using NDI1 was able to prevent AMPK‐mediated phosphorylation of YAP and to rescue CSC stemness. Genetic targeting of DGUOK using doxycycline‐inducible CRISPR/Cas9 was able to markedly induce tumor regression. Our findings reveal a novel role for mitochondrial dNTP metabolism in lung cancer tumor growth and progression, and implicate that the mitochondrial deoxynucleotide salvage pathway could be potentially targeted to prevent CSC‐mediated therapy resistance and metastatic recurrence.
A naturalistic investigation of cognitive-affective dysfunction in anorexia nervosa: The role of inefficiency.

OBJECTIVE Research has shown that rumination and negative affect are elevated in patients with anorexia nervosa (AN), but the underlying origins remain unclear. Drawing from the theoretical framework of the Goal Progress Theory of rumination, we propose that heightened feelings of "inefficiency" (i.e., low self-efficacy) in AN might play an important role in these dysfunctional cognitive-affective processes. METHOD Thirty-two weight-recovered participants with a history of AN and 32 healthy control participants filled out questionnaires regarding rumination and affect six times a day over a period of 2 weeks via ecological momentary assessment in real-life. RESULTS Analyses via hierarchical as well as conceptual process modeling suggest that while inefficiency is generally associated with more rumination and negative affect, additional amplifying mechanisms between these variables exist specifically in recovered participants with a history of AN. DISCUSSION Inefficiency as a core aspect of AN appears to trigger dysfunctional cognitive-affective processes which may contribute to vulnerability for AN.
Does the Rorschach Performance Assessment System (R-PAS) Differ from the Comprehensive System (CS) on Variables Relevant to Interpretation?

Abstract We examined the impact of the changes in administration and coding introduced by the Rorschach Performance Assessment System (R-PAS) relative to the Comprehensive System (CS) on the Rorschach response process, as manifested in variables relevant to interpretation. We also examined the efficiency of each system to obtain protocols in an optimal range of responses (R) for interpretation. As hypothesized, when comparing 50 CS and 50 R-PAS nonpatient protocols, R-PAS produced many more protocols in the optimal R range (18-27) than the CS (78% vs. 24%) and it eliminated the need for re-administration, which was required for five CS protocols. As expected, R was less variable with R-PAS, as were two variables derived from it, R8910% and Complexity. In addition, as expected because of different Form Quality tables, R-PAS showed notably fewer and less variable perceptual distortions than the CS, and an increase in more conventional perceptions. The other 58 variables showed no reliable differences in means or standard deviations, though modest power precluded definitive inferences about equivalence. Overall, our results support previous findings about the benefit of R-PAS to obtain protocols in an optimal range for interpretation, while keeping the core manifestations of the response process unchanged.
Chlorophyllin in the intra-uterine development of mice exposed or not to cyclophosphamide - doi: 10.4025/actascihealthsci.v35i2.12470

Chlorophyllin, a sodium-copper salt synthesized from chlorophyll, has already proved to have anticlastogenic, antimutagenic and anticarcinogenic activity, however few are the studies in the teratogenicity area. The present study evaluated the effects of chlorophyllin in intra-uterine development of mice exposed or not to cyclophosphamide. Pregnant females were divided into 8 groups of 15 animals each, G01 - PBS (0.1 mL 10.0 -1 g) orally; G02 - cyclophosphamide (20.0 mg kg -1 ) i.p.; G03, G04 and G05 - chlorophyllin at concentrations of (5.0, 10.0 and 15.0 mg kg -1 ) orally; G06, G07 and G08 (5.0, 10.0 and 15.0 mg kg -1 ) orally, of chlorophyllin, respectively, and (20.0 mg kg -1 ) i.p. of cyclophosphamide. In the 18 th day the females were submitted to laparotomy and females and fetuses analyzed. The results showed that the chlorophyllin was not effective in protecting the reproductive parameters as well as teratogenicity. Finally, it was observed that the presence of chlorophyllin increased the frequency of some malformations when combined with cyclophosphamide. However, it was not teratogenic and not embryo lethal in this experimental design.
Implementing a peer-support programme by group videoconferencing for isolated carers of people with dementia

Introduction Carers support programmes are commonly delivered in person, limiting attendance opportunities for rural carers and others who have access barriers. Studies using technology typically use text-based forums rather than real-time technology such as videoconferencing (VC). Delivering home-based carers support programmes by VC may mitigate barriers for accessing support. We report implementation findings for delivering a telehealth peer-support programme for isolated carers of people with dementia. Methods Participants were recruited through aged care providers, peak bodies and media activities. Inclusion criteria were primary dementia caregiver with Internet access and being socially or geographically isolated. The study design was a staggered randomised waitlist design. Measures included the UCLA Loneliness Scale (ULS-6) and selected scales from the e-Health Literacy Questionnaire. Recruitment activities utilised digital processes. Participants completed a six-week programme delivered by VC. Qualitative data comprised logs detailing administration and IT procedures and difficulties. Post programme, 28 participants undertook semi-structured interviews. Data were analysed using descriptive statistics and thematic analysis. Results There were 16 groups comprising 69 participants located throughout Australia, with 87% using their own devices. Technical issues were few but included connection problems, which were compounded by low digital literacy skills. Qualitative data themes included changing perceptions in using technology, differences in communicating by VC and technical support required. Recruitment activities were time-consuming and would benefit from IT tailored for group-based work. Eight groups continued to meet on a self-organised basis. Discussion Providing peer-support groups using telehealth may have the potential to develop self-sustaining peer networks for isolated caregivers of people with dementia.
The effect of nutrition education on knowledge, attitude and practice of type 1 diabetic patients from Aligoodarz

چکیده: زمینه و هدف: مراقبت های پزشکی- تغذیه ای در بیماران مبتلا به دیابت از بروز و پیشرفت عوارض جلوگیری می کند. یافته های متناقضی در زمینه تأثیر آگاهی بر بهبود کنترل متابولیک بیماران مبتلا به دیابت نوع 1 وجود دارد. این بررسی با هدف تعیین تأثیر آموزش تغذیه بر آگاهی، نگرش و عملکرد مبتلایان به دیابت نوع 1 انجام شد. روش بررسی: در یک مطالعه مداخله ای قبل و بعد کلیه بیماران مبتلا به دیابت نوع 1 شهرستان الیگودرز (30 نفر) مورد بررسی قرار گرفتند. در شروع مطالعه فراسنج های بیوشیمیایی با روش های استاندارد اندازه گیری و پرسشنامه KAP (Knowledge Attitude Practices) سپس یاد آمد خوراک سه روزه، تکمیل گردید. بیماران به مدت 12 ساعت در زمینه کلیات بیماری دیابت، عوارض آن، نحوه پیشگیری و مراقبت های لازم جهت به تأخیر انداختن عوارض و تغذیه در بیماری دیابت و جانشین های مواد غذایی آموزش دیدند و سه ماه بعد از آموزش مجددا فراسنج های بیوشیمیایی اندازه گیری و پرسشنامه KAP و یادآمد خوراک تکمیل شد و داده های قبل و بعد از آموزش مقایسه شدند. داده ها با استفاده از نرم افزارهای SPSS و Nuatritionist3 و آزمون های آماری t مزدوج و مک نمار تجزیه و تحلیل شدند. یافته ها: نتایج این مطالعه نشان داد که آموزش، تغییر معنی داری در میانگین وزن، نمایه توده بدنی (BMI)، فشــارخون سیستولیک و دیاستولیک، میزان مصرف انرژی و درشت مغذی ها ایجاد نکرد (05/0p>)، ولی باعث کاهش معنی داری در میزان قند خون ناشتا، کلسترول تام، درصد هموگلوبین گلیکوزیله (HbAlc)، LDL (Low Density Lipoprotein) سرم و تعداد دفعات هیپوگلیسمی در هفته گردید (001/0p
Chronic Elevation of Endothelin-1 Alone May Not Be Sufficient to Impair Endothelium-Dependent Relaxation.

Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide considered to be causally implicated in hypertension and the development of cardiovascular disease. Increased ET-1 is commonly associated with reduced NO bioavailability and impaired vascular function; however, whether chronic elevation of ET-1 directly impairs endothelium-dependent relaxation (EDR) remains elusive. Herein, we report that (1) prolonged ET-1 exposure (ie, 48 hours) of naive mouse aortas or cultured endothelial cells did not impair EDR or reduce eNOS (endothelial NO synthase) activity, respectively (P>0.05); (2) mice with endothelial cell-specific ET-1 overexpression did not exhibit impaired EDR or reduced eNOS activity (P>0.05); (3) chronic (8 weeks) pharmacological blockade of E-1 receptors in obese/hyperlipidemic mice did not improve aortic EDR or increase eNOS activity (P>0.05); and (4) vascular and plasma ET-1 did not inversely correlate with EDR in resistance arteries isolated from human subjects with a wide range of ET-1 levels (r=0.0037 and r=-0.1258, respectively). Furthermore, we report that prolonged ET-1 exposure downregulated vascular UCP-1 (uncoupling protein-1; P<0.05), which may contribute to the preservation of EDR in conditions characterized by hyperendothelinemia. Collectively, our findings demonstrate that chronic elevation of ET-1 alone may not be sufficient to impair EDR.
Differential Expression of Parietal Epithelial Cell and Podocyte Extracellular Matrix Proteins in Focal Segmental Glomerulosclerosis and Diabetic Nephropathy.

In healthy glomeruli, PEC-derived extracellular matrix (ECM) proteins include Laminin β1 (LAMB1), Perlecan and collagen type IV α2 (COL4A2), and podocyte-specific ECM proteins include Laminin β2 (LAMB2), Agrin and collagen type IV α4 (COL4A4). This study aimed to define individual ECM protein isoform expression by PECs in both experimental and human focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy (DN), and to determine if changes were CD44-dependent. In experimental FSGS induced with a cytotoxic podocyte antibody, and in the BTBR ob/ob mouse model of DN, PEC-derived protein staining was significantly increased in PECs. Dual staining also showed de novo expression of the podocyte-specific ECM proteins LAMB2 and Agrin in PECs. Similar findings were observed in biopsies from patients with FSGS and DN. Increases in individual ECM proteins co-localized with CD44 in PECs in disease. To determine the role of CD44, FSGS was induced in CD44-/- and CD44+/+ mice. PEC staining for Perlecan, COL4A2, LAMB2 and Agrin were significantly lower in diseased CD44-/- mice compared to diseased CD44+/+ mice. These results show that in experimental and human FSGS and DN, PECs typically in an activated state, produce both PEC-derived and podocyte-specific ECM protein isoforms, and that the majority of these changes were dependent on CD44.
Biomechanics of two-thumb versus two-finger chest compression for cardiopulmonary resuscitation in an infant manikin model

Objective The loading force applied in infant external chest compression (ECC) has not been determined. The objective of this crossover study was to quantify the actual force involved in two-thumb (TT)-encircling hands and two-finger (TF) methods during infant cardiopulmonary resuscitation. Methods A total of 42 emergency medical professionals performed lone rescuer infant external chest compression (ECC) with TF and TT methods. The order of two methods was arranged randomly, with an interval of 30 min in between. The force was collected by MatScan as primary outcomes. The secondary outcomes, quality of chest compressions, and fatigue level were also recorded by SkillReporter and perceived exertion scale. Results Using the TT method, the rescuers performed cardiopulmonary resuscitation (CPR) with higher ECC quality, but more incomplete recoil than they did using the TF method. The mean compression forces delivered in the first and second minutes were 3.53 ± 1.27 kg and 3.22 ± 1.11 kg (P = 0.012) for TF and 4.11 ± 1.80 kg and 4.04 ± 1.83 kg (P = 0.568) for TT, respectively. Pairwise comparison indicates that the compression force delivered through the TF method during the first and second minute of ECC were inferior to that delivered through the TT method. The TF method involved greater perceived exertion than the TT method (5.27 ± 4.69 vs. 4.02 ± 2.31; P = 0.007). The median perceived exertions for the TF and TT methods were 5 and 4, respectively. Conclusion For infant CPR, the TT method involved greater loading force, lower fatigue, and higher overall ECC quality than the TF method. The optimal compression force is about 3.8–4.3 kg.
Surgical Treatment of Bilateral Tibia Deformity in a 9-Year-Old Child Suffering from Osteogenesis Imperfecta Type III: A Case Report

Patient: Male, 9 Final Diagnosis: Osteogenesis imperfecta type III Symptoms: Walking difficulties Medication: — Clinical Procedure: Osteotomies and realignment of bone deformity Specialty: Orthopedics and Traumatology Objective: Congenital defects/diseases Background: Osteogenesis imperfecta is a rare inherited connective tissue disorder that is mainly characterized by long bone deformities and increased susceptibility to bone fractures. The aim of this study was to present a surgical technique in a child suffering from osteogenesis imperfecta and progressive, severe bowing deformity of both tibias, as an alternative method to advanced, innovative surgical systems. Case Report: A 9-year-old child (male) was referred to our orthopedic clinic for inability to walk independently due to extreme anterior bowing of both tibias. After the diagnosis of osteogenesis imperfecta type III was established, bilateral surgical treatment with multiple osteotomies and intramedullary, flexible Titanium Elastic Nail System (TENS) nails was decided. Six months post-operatively callus formation was obvious in x-rays and at the latest follow-up (1 year post-operatively) the patient regained the ability to walk independently. Conclusions: In types of osteogenesis imperfecta which are characterized by extreme deformities (type III) surgical intervention seems to be the only solution for these patients to walk again. We present a relatively simple technique of correcting such deformities, indicating that no matter which technique will be used (simple or more complicated) the final goal should be to restore the walking ability with as little complications as possible.