Miracle-dz/UniFAR-FTUs huggingface dataset:
Unbound bilirubin levels in phototherapy‐treated preterm infants receiving soy‐based lipid emulsion

Phototherapy is an effective treatment for neonatal jaundice. Treatment indication uses total serum bilirubin (TSB), although unbound bilirubin (Bf) more accurately predicts disability risk. The goals of this investigation were to examine the response of Bf and TSB to phototherapy in preterm infants, and we hypothesized that (i) TSB and Bf respond differently; (ii) the relationship between TSB and Bf is altered; and (iii) unexpected Bf elevations are found.
Withdrawing mycophenolate mofetil in treating a young kidney transplant recipient with COVID-19

Abstract Rationale: Coronavirus disease 2019 (COVID-19) is a novel infectious disease and became a global issue. Treatment of COVID-19 especially in solid organ transplant recipients is empirical and controversial, especially the adjustment of the immunosuppressants. Patient concerns: A 29-year-old kidney transplant recipient with the symptoms of COVID-19 pneumonia. Diagnoses: COVID-19 pneumonia after kidney transplantation. Interventions: He was treated with modified immunosuppressants (unchanged dose of tacrolimus and oral corticosteroids while discontinuing mycophenolate mofetil (MMF)), antibiotics, interferon α-2b inhalation and traditional Chinese medicine. Outcomes: He recovered from COVID-19 pneumonia after 29 days of hospitalization. And the renal function (measured as blood urea nitrogen, serum creatinine, and urine protein) returned to normal. Lessons: In certain group of COVID-19 (e.g., mild to moderate cases, young patients without comorbidities), a reduction instead of an overall withdrawal of immunosuppressant in kidney transplant recipients is feasible.
Role of 5‐HT1A and 5‐HT3 receptors in serotonergic activation of sensory neurons in relation to itch and pain behavior in the rat

Serotonin (5‐hydroxytryptamine, 5‐HT) released by platelets, mast cells, and immunocytes is a potent inflammatory mediator which modulates pain and itch sensing in the peripheral nervous system. The serotonergic receptors expressed by primary afferent neurons involved in these sensory functions are not fully identified and appear to be to a large extent species dependent. Moreover, the mechanisms through which 5‐HT receptor activation is coupled to changes in neuronal excitability have not been completely revealed. Using a combination of in vitro (calcium and voltage imaging and patch‐clamp) and in vivo behavioral methods, we used both male and female Wistar rats to provide evidence for the involvement of two 5‐HT receptor subtypes, 5‐HT1A and 5‐HT3, in mediating the sustained and transient effects, respectively, of 5‐HT on rat primary afferent neurons involved in pain and itch processing. In addition, our results are consistent with a model in which sustained serotonergic responses triggered via the 5‐HT1A receptor are due to closure of background potassium channels, followed by membrane depolarization and action potentials, during which the activation of voltage‐gated calcium channels leads to calcium entry. Our results may provide a better understanding of mammalian serotonergic itch signaling.
Supramolecular Packing Drives Morphological Transitions of Charged Surfactant Micelles

Abstract The shape and size of self‐assembled structures upon local organization of their molecular building blocks are hard to predict in the presence of long‐range interactions. Combining small‐angle X‐ray/neutron scattering data, theoretical modelling, and computer simulations, sodium dodecyl sulfate (SDS), over a broad range of concentrations and ionic strengths, was investigated. Computer simulations indicate that micellar shape changes are associated with different binding of the counterions. By employing a toy model based on point charges on a surface, and comparing it to experiments and simulations, it is demonstrated that the observed morphological changes are caused by symmetry breaking of the irreducible building blocks, with the formation of transient surfactant dimers mediated by the counterions that promote the stabilization of cylindrical instead of spherical micelles. The present model is of general applicability and can be extended to all systems controlled by the presence of mobile charges.
Connexin 43 gap junctional intercellular communication inhibits evx1 expression and joint formation in regenerating fins

ABSTRACT The gap junction protein Connexin 43 (Cx43) contributes to cell fate decisions that determine the location of fin ray joints during regeneration. Here, we provide insights into how Cx43, expressed medially, influences changes in gene expression in lateral skeletal precursor cells. Using the Gap27 peptide inhibitor specific to Cx43, we show that Cx43-gap junctional intercellular communication (GJIC) influences Cx43-dependent skeletal phenotypes, including segment length. We also demonstrate that Cx43-GJIC influences the expression of the Smp/β-catenin pathway in the lateral skeletal precursor cells, and does not influence the Sema3d pathway. Moreover, we show that the cx43lh10 allele, which has increased Cx43 protein levels, exhibits increased regenerate length and segment length. These phenotypes are rescued by Gap27, suggesting that increased Cx43 is responsible for the observed Cx43 phenotypes. Finally, our findings suggest that inhibition of Cx43 hemichannel activity does not influence Cx43-dependent skeletal phenotypes. These data provide evidence that Cx43-GJIC is responsible for regulating cell fate decisions associated with appropriate joint formation in the regenerating fin. Summary: Expression and phenotypic analyses reveal that connexin 43 gap junctional intercellular communication (Cx43-GJIC) regulates cell fate decisions in the lateral skeletal precursor cells. Inhibition of Cx43-GJIC favors expression of evx1 and joint formation.
Computing schizophrenia: ethical challenges for machine learning in psychiatry

Abstract Recent advances in machine learning (ML) promise far-reaching improvements across medical care, not least within psychiatry. While to date no psychiatric application of ML constitutes standard clinical practice, it seems crucial to get ahead of these developments and address their ethical challenges early on. Following a short general introduction concerning ML in psychiatry, we do so by focusing on schizophrenia as a paradigmatic case. Based on recent research employing ML to further the diagnosis, treatment, and prediction of schizophrenia, we discuss three hypothetical case studies of ML applications with view to their ethical dimensions. Throughout this discussion, we follow the principlist framework by Tom Beauchamp and James Childress to analyse potential problems in detail. In particular, we structure our analysis around their principles of beneficence, non-maleficence, respect for autonomy, and justice. We conclude with a call for cautious optimism concerning the implementation of ML in psychiatry if close attention is paid to the particular intricacies of psychiatric disorders and its success evaluated based on tangible clinical benefit for patients.
Human milk oligosaccharide supplementation in irritable bowel syndrome patients: A parallel, randomized, double‐blind, placebo‐controlled study

Human milk oligosaccharides safely and beneficially impact bifidobacteria abundance in healthy adults, while their effects in patients with irritable bowel syndrome (IBS) are unknown. Hence, we aimed to determine the dose of 4:1 mix of 2’‐O‐fucosyllactose and Lacto‐N‐neotetraose (2’FL/LNnT) that increases fecal bifidobacteria abundance without aggravating overall gastrointestinal symptoms in IBS patients in a randomized, double‐blind, controlled study. Additionally, the impact of 2’FL/LNnT on the fecal bacterial profile was assessed.
Generalized pustular psoriasis-like drug eruption manifested by systemic glucocorticosteroid in a patient without IL36RN mutation or an immunological disorder

183 the clinical course is benign. Ahmed et al. reported that 12 of 51 patients with untreated CRDD experienced spontaneous resolution of skin lesions with an average delay of 38 months [7]. Our patient had multiple lesions over the whole body, but there was no life-threatening disease. The patient is currently under observation without treatment. It took one year for the skin lesions to disappear, which is consistent with previous reports of CRDD. However, the nasal, pharyngeal and bone lesions persisted for more than three years. Thus, this case suggests that even in systemic RDD cases, the skin lesions can regress earlier than extranodal lesions. As RDD patients may initially present to dermatology departments, dermatologists should be aware of the clinical features of RDD. Furthermore, the natural course of this disorder should be known in order to avoid overtreatment.
Sacubitril/Valsartan Improves Cardiac Function and Decreases Myocardial Fibrosis Via Downregulation of Exosomal miR‐181a in a Rodent Chronic Myocardial Infarction Model

Background Exosomes are small extracellular vesicles that function as intercellular messengers and effectors. Exosomal cargo contains regulatory small molecules, including miRNAs, mRNAs, lncRNAs, and small peptides that can be modulated by different pathological stimuli to the cells. One of the main mechanisms of action of drug therapy may be the altered production and/or content of the exosomes. Methods and Results We studied the effects on exosome production and content by neprilysin inhibitor/angiotensin receptor blockers, sacubitril/valsartan and valsartan alone, using human‐induced pluripotent stem cell‐derived cardiomyocytes under normoxic and hypoxic injury model in vitro, and assessed for physiologic correlation using an ischemic myocardial injury rodent model in vivo. We demonstrated that the treatment with sacubitril/valsartan and valsartan alone resulted in the increased production of exosomes by induced pluripotent stem cell‐derived cardiomyocytes in vitro in both conditions as well as in the rat plasma in vivo. Next‐generation sequencing of these exosomes exhibited downregulation of the expression of rno‐miR‐181a in the sacubitril/valsartan treatment group. In vivo studies employing chronic rodent myocardial injury model demonstrated that miR‐181a antagomir has a beneficial effect on cardiac function. Subsequently, immunohistochemical and molecular studies suggested that the downregulation of miR‐181a resulted in the attenuation of myocardial fibrosis and hypertrophy, restoring the injured rodent heart after myocardial infarction. Conclusions We demonstrate that an additional mechanism of action of the pleiotropic effects of sacubitril/valsartan may be mediated by the modulation of the miRNA expression level in the exosome payload.
Cancer‐associated adipocytes promote pancreatic cancer progression through SAA1 expression

Although pancreatic cancer often invades peripancreatic adipose tissue, little information is known about cancer‐adipocyte interaction. We first investigated the ability of adipocytes to de‐differentiate to cancer‐associated adipocytes (CAAs) by co‐culturing with pancreatic cancer cells. We then examined the effects of CAA‐conditioned medium (CAA‐CM) on the malignant characteristics of cancer cells, the mechanism underlying those effects, and their clinical relevance in pancreatic cancer. When 3T3‐L1 adipocytes were co‐cultured with pancreatic cancer cells (PANC‐1) using the Transwell system, adipocytes lost their lipid droplets and changed morphologically to fibroblast‐like cells (CAA). Adipocyte‐specific marker mRNA levels significantly decreased but those of fibroblast‐specific markers appeared, characteristic findings of CAA, as revealed by real‐time PCR. When PANC‐1 cells were cultured with CAA‐CM, significantly higher migration/invasion capability, chemoresistance, and epithelial‐mesenchymal transition (EMT) properties were observed compared with control cells. To investigate the mechanism underlying these effects, we performed microarray analysis of PANC‐1 cells cultured with CAA‐CM and found a 78.5‐fold higher expression of SAA1 compared with control cells. When the SAA1 gene in PANC‐1 cells was knocked down with SAA1 siRNA, migration/invasion capability, chemoresistance, and EMT properties were significantly attenuated compared with control cells. Immunohistochemical analysis on human pancreatic cancer tissues revealed positive SAA1 expression in 46/61 (75.4%). Overall survival in the SAA1‐positive group was significantly shorter than in the SAA1‐negative group (P = .013). In conclusion, we demonstrated that pancreatic cancer cells induced de‐differentiation in adipocytes toward CAA, and that CAA promoted malignant characteristics of pancreatic cancer via SAA1 expression, suggesting that SAA1 is a novel therapeutic target in pancreatic cancer.
COVID‐19 in a child with severe aplastic anemia

COVID-19 in a child with severe aplastic anemiaYunus Murat Akcabelen1, Ayca Koca Yozgat1, Asli Nur Parlakay2, Nese Yarali11 Department of Pediatric Hematology, Ankara City Hospital Children’s Hospital, Turkiye2 Department of Pediatric Infectious Disease, Ankara City Hospital Children’s Hospital, TurkiyeArticle type: Letter to the editorRunning Title: COVID-19 in pediatric aplastic anemiaKey words: COVID-19, children, aplastic anemiaDisclosures: noneWord counts: 625
Patient safety issues associated with the use of compounded medicines as alternatives to approved pharmaceutical products in Europe and how best practice can improve outcomes.

BACKGROUND Pharmaceutical compounding allows individuals with special requirements access to medicines. Compounding can also be used to provide cheaper alternatives to commercially produced medicines which may be less strictly regulated than those commercially produced as they do not require marketing authorisation. OBJECTIVE This review describes the issues and potential risks associated with compounded medicines and equally importantly identifies best practices. METHODS To establish reports about lack of effectiveness, adverse events and medication errors occurring with compounded pharmaceuticals, a literature search was conducted of PubMed, Embase and MEDLINE databases for relevant cases in European countries which were published between 2003 and 2018. Case reports/series that described instances of successful use of compounded medicines over the same period were also identified. RESULTS Overall, 12 case reports/case series describing problems associated with compounded medicines in Europe have been identified. Sources of patient risk associated with compounded medicines include lack of quality, safety and efficacy data, preparation and labelling errors, and improper storage and handling practices. CONCLUSIONS Several case reports/series describing instances of overdose, medication errors and adverse events associated with compounded medications were reviewed. The number of affected patients was relatively small, but many were children and two adult patients experienced permanent sequelae. The number of incidents associated with compounded medicines is unknown, and so these numbers should be interpreted with caution. When licensed medicines are available, the use of compounded medicines can put patients at unnecessary risk which should be avoided. Stricter regulation is necessary to prevent similar cases from occurring in the future as the European market for compounded medications grows. Pharmacists can promote best practices in compounding through professional organisations. Future recommended actions are: 1. Stricter regulation is necessary to prevent similar cases from occurring in the future as the European market for compounded medications grows. 2. A comprehensive pan-European survey to gain a greater understanding of compounding procedures and techniques. This would provide valuable information to the benefit of hospital systems and their patients. 3. The results of the survey can then be used to improve the knowledge and quality control of compounded medicines for the good of patient safety.
Effects of innovative hip-knee-ankle interlimb coordinated robot training on ambulation, cardiopulmonary function, depression, and fall confidence in acute hemiplegia.

BACKGROUND While Walkbot-assisted locomotor training (WLT) provided ample evidence on balance and gait improvements, the therapeutic effects on cardiopulmonary and psychological elements as well as fall confidence are unknown in stroke survivors. OBJECTIVE The present study aimed to compare the effects of Walkbot locomotor training (WLT) with conventional locomotor training (CLT) on balance and gait, cardiopulmonary and psychological functions and fall confidence in acute hemiparetic stroke. METHODS Fourteen patients with acute hemiparetic stroke were randomized into either the WLT (60-minute physical therapy +30-minute Walkbot-assisted gait training) or CLT (60 min physical therapy +30 min gait training) groups, 7 days/week over 2 weeks. Clinical outcomes included the Berg balance scale (BBS), functional ambulation category (FAC), heart rate (HR) and Borg rating of perceived exertion (BRPE), Beck depression inventory-II (BDI-II), and the activities-specific balance confidence (ABC) scale. The analysis of covariance (ANCOVA) was conducted at P < 0.05. RESULTS ANCOVA showed that WLT showed superior effects, compared to CLT, on FAC, HR, BRPE, BDI-II, and ABC scale (P < 0.05), but not on BBS (P = 0.061). CONCLUSIONS Our results provide novel, promising clinical evidence that WLT improved balance and gait function as well as cardiopulmonary and psychological functions, and fall confidence in acute stroke survivors who were unable to ambulate independently.
Anterior lumbar compared to oblique lumbar interbody approaches for multilevel fusions to the sacrum in adults with spinal deformity and degeneration.

OBJECTIVE In adult spinal deformity and degenerative conditions of the spine, interbody fusion to the sacrum often is performed to enhance arthrodesis, induce lordosis, and alleviate stenosis. Anterior lumbar interbody fusion (ALIF) has traditionally been performed, but minimally invasive oblique lumbar interbody fusion (OLIF) may or may not cause less morbidity because less retraction of the abdominal viscera is required. The authors evaluated whether there was a difference between the results of ALIF and OLIF in multilevel anterior or lateral interbody fusion to the sacrum. METHODS Patients from 2013 to 2018 who underwent multilevel ALIF or OLIF to the sacrum were retrospectively studied. Inclusion criteria were adult spinal deformity or degenerative pathology and multilevel ALIF or OLIF to the sacrum. Demographic, implant, perioperative, and radiographic variables were collected. Statistical calculations were performed for significant differences. RESULTS Data from a total of 127 patients were analyzed (66 OLIF patients and 61 ALIF patients). The mean follow-up times were 27.21 (ALIF) and 24.11 (OLIF) months. The mean surgical time was 251.48 minutes for ALIF patients and 234.48 minutes for OLIF patients (p = 0.154). The mean hospital stay was 7.79 days for ALIF patients and 7.02 days for OLIF patients (p = 0.159). The mean time to being able to eat solid food was 4.03 days for ALIF patients and 1.30 days for OLIF patients (p < 0.001). After excluding patients who had undergone L5-S1 posterior column osteotomy, 54 ALIF patients and 41 OLIF patients were analyzed for L5-S1 radiographic changes. The mean cage height was 14.94 mm for ALIF patients and 13.56 mm for OLIF patients (p = 0.001), and the mean cage lordosis was 15.87° in the ALIF group and 16.81° in the OLIF group (p = 0.278). The mean increases in anterior disc height were 7.34 mm and 4.72 mm for the ALIF and OLIF groups, respectively (p = 0.001), and the mean increases in posterior disc height were 3.35 mm and 1.24 mm (p < 0.001), respectively. The mean change in L5-S1 lordosis was 4.33° for ALIF patients and 4.59° for OLIF patients (p = 0.829). CONCLUSIONS Patients who underwent multilevel OLIF and ALIF to the sacrum had comparable operative times. OLIF was associated with a quicker ileus recovery and less blood loss. At L5-S1, ALIF allowed larger cages to be placed, resulting in a greater disc height change, but there was no significant difference in L5-S1 segmental lordosis.
Understanding fear of childbirth among underrepresented populations in the United States

The purpose of this study was to expand our understanding of fear of childbirth (FOC) by examining the interplay between individual, provider, identity, and culture among women historically underrepresented in FOC research to develop a deeper understanding of FOC. Purposive sampling was used to recruit 22 participants into three different focus groups, each with a unique demographic makeup. The results provide evidence that people’s birth experiences and their experiences with fear surrounding childbirth are affected by many other social mechanisms, including relationships with providers, birth setting, race, class, gender, sexual orientation, and ethnicity.
Grade 1 Vertebral Fractures Identified by Densitometric Lateral Spine Imaging Predict Incident Major Osteoporotic Fracture Independently of Clinical Risk Factors and Bone Mineral Density in Older Women

Because prevalent vertebral fracture (VF) is a strong predictor of future fractures, they are important to identify in clinical practice as osteoporosis medications are effective and can be used to reduce fracture risk in postmenopausal women with VF. Lateral spine imaging (LSI) with dual‐energy X‐ray absorptiometry (DXA) can be used to diagnose VFs accurately but is not widespread in clinical practice. The prognostic value of grade 1 (20% to 25% compression) VFs diagnosed by LSI with DXA has been insufficiently studied. The aim of this study was to determine if grade 1 VF is associated with incident fracture in older women. Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a population‐based study of 3028 older women from Gothenburg, Sweden. Included women were 75 to 80 years of age at baseline, answered questionnaires, and were scanned with DXA (Discovery A, Hologic, Waltham, MA, USA). LSI was used to diagnose VFs, which were classified using the Genant semiquantitative method. Cox regression models were used to estimate the association between VFs at baseline and X‐ray–verified incident fractures, with adjustment for confounders. Women with a grade 1 VF (n = 264) or a grade 2–3 VF (n = 349) were compared with women without any fracture (n = 1482). During 3.6 years (median, interquartile range [IQR] 1.5 years) of follow‐up, 260 women had any incident fracture and 213 a major osteoporotic fracture (MOF). Women with only grade 1 VF had increased risk of any fracture (hazard ratio [HR] = 1.67; 95% confidence interval [CI] 1.18–2.36) and MOF (HR = 1.86; 95% CI 1.28–2.72). For MOF, this association remained after adjustment for clinical risk factors and femoral neck bone mineral density (BMD). In conclusion, grade 1 VFs were associated with incident MOF, also after adjustment for clinical risk factors and BMD, indicating that all VF identified by DXA should be considered in the evaluation of fracture risk in older women. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.