Miracle-dz/UniFAR-FTUs huggingface dataset:
Aberrant retinoic acid production in the decidua: Implications for pre‐eclampsia

Fine‐tuning of the endometrium during the evanescent ‘window of implantation’ relies upon an array of diverse and redundant signaling molecules, particularly the ovarian steroids E2 and P4, but also growth factors, eicosanoids, and vitamins including the vitamin A compounds (retinoids). Pregnancy complications such as preeclampsia (PE) can result from aberrations in the production or function of these molecules that arise during this critical period of decidual development. Such aberrations may be reflected by incomplete decidualization, reduced spiral artery modification, and/or loss of immune tolerance to the developing fetus. Our understanding of the role of the active retinoid metabolite all‐trans retinoic acid (RA) in maintaining immune balance in certain tissues, along with data describing its role in decidualization, present a compelling argument that aberrant RA signaling in the decidua can play a significant role in the etiology of PE. Recent findings that decidualization and expression of the anti‐angiogenic gene product, ‘soluble fms‐like tyrosine kinase‐1’ (sFLT1) are negatively correlated and that sFLT1 expression is directly inhibited by RA, provide additional evidence of the critical role of this retinoid in regulating early vascular development in the decidua. This review provides insight into the production and function of RA in the decidua and how modifications in its metabolism and signaling might lead to certain pregnancy disorders such as PE.
Diet and Mental Health: Review of the Recent Updates on Molecular Mechanisms

Over the last decades, there has been a substantial increase in the prevalence of mental health disorders, including an increased prevalence of depression, anxiety, cognitive, and sleep disorders. Diet and its bioactive components have been recognized among the modifiable risk factors, possibly influencing their pathogenesis. This review aimed to summarize molecular mechanisms underlying the putative beneficial effects toward brain health of different dietary factors, such as micro- and macronutrient intake and habits, such as feeding time and circadian rhythm. The role of hormonal homeostasis in the context of glucose metabolism and adiponectin regulation and its impact on systemic and neuro-inflammation has also been considered and deepened. In addition, the effect of individual bioactive molecules exerting antioxidant activities and acting as anti-inflammatory agents, such as omega-3 fatty acids and polyphenols, considered beneficial for the central nervous system via modulation of adult neurogenesis, synaptic and neuronal plasticity, and microglia activation has been summarized. An overview of the regulation of the gut–brain axis and its effect on the modulation of systemic inflammation and oxidative stress has been provided. Finally, the impact of bioactive molecules on inflammation and oxidative stress and its association with brain health has been summarized.
Acute pancreatitis in a COVID-19 patient

Editor We read with interest Spinelli and Pellino’s Leading Article1, highlighting their experience of COVID-19, a global pandemic that is rapidly changing and challenging the scope of surgical practice2. Recent intercollegiate guidance has recommended a drastic change of approach in the management of surgical patients, including the suspension of all but emergency operations3. We highlight a case of acute pancreatitis in a patient with recently diagnosed COVID-19. A 59-year-old female patient, with a history of cholecystectomy and thrombophilia, initially presented to the emergency department with fever, cough, sore throat and myalgia having recently returned from a cruise in the Caribbean. Polymerase Chain Reaction confirmed COVID-19 and she was treated with simple supportive measures. She was commenced on intravenous vancomycin for a streptococcal pneumonia complicating COVID-19 infection, and discharged on day 5 with a course of doxycycline. Five days following discharge, she was readmitted with fever, abdominal pain and constipation, and treated for presumed adhesional bowel obstruction. Laboratory investigations demonstrated a white cell count of 14⋅3× 109/l, Creactive protein of 62⋅7 g/l, international normalized ratio (INR) of 5⋅2, and normal liver function. Unfortunately, no amylase was done on admission. As symptoms were not improving with conservative management, a CT was obtained on day 3. This demonstrated a previously atrophic pancreas that had increased markedly in size and had features of diffuse oedematous changes, suspicious for acute pancreatitis. The patient was managed conservatively and discharged after 7 days. The aetiology of pancreatitis in this case is idiopathic given the history of cholecystectomy, minimal alcohol use and lack of precipitating risk factors. Up to 10 per cent of acute pancreatitis is thought to have an infectious aetiology through an immune-mediated inflammatory response, most notably mumps and Coxsackie B viruses4. The recent positive COVID-19 diagnosis and reports of gastrointestinal symptoms in this disease raise the suspicion that there may be an association between this novel virus and acute pancreatitis. E. R. Anand , C. Major, O. Pickering and M. Nelson Department of General Surgery, St Mary’s Hospital, Isle of Wight NHS Trust, Newport, UK
Studies on the X-organ of eyestalk and the photoperiod for the control of gonadal maturation in a freshwater prawn, Macrobrachium nipponense(De Haan)

To clarify the relations between photoperiodism and x-organ of eyestalks to the control of gonadal maturation in a freshwater prawn, Macrobrachium nipponense, the present investigation was performed with following examinations: 1) the influence of water temperature and daylength on the control of gonadal maturation, 2) the effect of eyestalk ablation on the gonadal maturation, 3) the seasonal variation of histology of MEX-organ (medulla externa X-organ) in the eyestalk. In previtellogenesis period (DecemberMarch) and vitellogenesis period (AprilMay), gonadal maturation was considerablely influnced by water temperature. In these periods, GSI increased and gonads were matured with water temperature rising without regard to photoperiod conditions (12L/12D and 15L/9D). In spawning period (JuneAugust), however, gonadal maturation was influenced by photoperiod condition. While high value of GSI was kept at long photoperiod regime (15L/9D), GSI was decreased at short photoperiod regime (12L/12D). In resting period (SeptemberNovember), no rematuration was occurred at all the experimental regimes combinated with water temperatures () and photoperiod (12L/12D, 15L/9D). Effect of X-organ which inhibite the gonadal maturation was stronger in resting period than that in previtellogenesis and ealy spawning periods by observations on the effectiveness of eyestalk ablation on the gonadal maturation. In MEX-organ of eyestalk, the number of neurosecretory cells of which size was over in diameter varied according to the reproductive cycle. The number of cells increased in resting period, and decreased in vitellogenesis period. Volume of Bellonci's organ, however, increased in vitellogenesis period in comparison with that in resting period.
Results 5 to 10 years after cataract surgery with primary IOL implantation in juvenile idiopathic arthritis-related uveitis.

PURPOSE To evaluate the results of cataract extraction with primary intraocular lens (IOL) implantation in patients with juvenile idiopathic arthritis (JIA) and uveitis related cataract. SETTING Department of Ophthalmology, Helsinki University Hospital, Finland. DESIGN Retrospective case series. METHODS All consecutive patients younger than 20 years with JIA-uveitis-related cataract undergoing cataract extraction with primary IOL implantation in 1 or both eyes at the Department of Ophthalmology, Helsinki University Hospital, Finland, from February 2000 to April 2012 were included. Twenty eligible patients with 26 operated eyes were identified; 14 were girls and 6 were boys. All patients had a follow-up of 5 years and 13 patients (65%; 16 eyes) reached 10 years of follow-up. RESULTS Twenty-six eyes of 20 patients were studied. Preoperative median corrected distance visual acuity (CDVA) was 0.05 in decimal notation. Median CDVA was 1.0 at 5 years and 0.9 at 10 years of follow-up. Two eyes did not reach CDVA 0.5 with the operation, and in 2 eyes CDVA decreased below 0.5 over the period of 3 to 5 years after the operation. Active uveitis during 3 and 12 months prior to surgery was a risk indicator for postoperative CDVA <0.5 at 5 years (P=0.005 and P=0.007, respectively). CONCLUSIONS Cataract extraction with primary IOL implantation provides long-standing good visual acuity for young patients with well-controlled JIA-related uveitis.
The presence of active brown adipose tissue determines cold-induced energy expenditure and oxylipin profiles in humans.

BACKGROUND Accumulating evidence links brown adipose tissue (BAT) to increased cold-induced energy expenditure (CIEE) and regulation of lipid metabolism in humans. BAT has also been proposed as a novel source for biologically active lipid mediators including polyunsaturated fatty acids (PUFAs) and oxylipins. However, little is known about cold-mediated differences in energy expenditure and various lipid species between individuals with detectable BAT (BATpos) and those without (BATneg). METHODS Here we investigated a unique cohort of matched BATpos and BATneg individuals identified by [18F]-FDG PET/CT. BAT function, CIEE and circulating oxylipins, were analyzed before and after short-term cold exposure using [18F]-FDG PET/CT, indirect calorimetry and high-resolution mass spectrometry, respectively. RESULTS We found that active BAT is the major determinant of cold-induced energy expenditure since only BATpos individuals experienced significantly increased energy expenditure in response to cold. A single bout of moderate cold exposure resulted in the dissipation of additional 20kcal excess energy in BATpos but not in BATneg individuals. The presence of BAT was associated with a unique systemic PUFA and oxylipin profile characterized by increased levels of anti-inflammatory ω3 fatty acids as well as cytochrome P450 products but decreased concentrations of some pro-inflammatory hydroxyeicosatetraenoic acids when compared to BATneg individuals. Notably, cold exposure raised circulating levels of various lipids, including the recently identified BATokines DiHOME and 12-HEPE, only in BATpos subjects. CONCLUSIONS In summary, our data emphasize that BAT in humans is a major contributor towards cold-mediated energy dissipation and a critical organ in the regulation of the systemic lipid pool.
Health-related quality-of-life after radical cystectomy among Norwegian men and women compared to the general population

Abstract Objective: The aim of this study was to assess health-related quality-of-life (HRQoL) in men and women operated on with radical cystectomy, compared to the general Norwegian population. Materials and methods: All patients with bladder cancer who had undergone radical cystectomy (RC) between 2011–2017 and either received ileal conduit (IC) or orthotopic neobladder (ONB) as urinary diversion were included in a cross-sectional study. HRQoL and sociodemographic data was collected and measured with a questionnaire consisting of the generic EORTC QLQ-C30.v3 and the cancer specific EORTC QLQ-BLM30 and compared to a general population sample. Results: Of the 220 invited patients, 173 patients (78.6%) returned the questionnaires. The global quality-of-life (QoL) score was comparable with the general population. Women had significantly higher fatigue score, worse future perspective and symptoms like bloating, compared to male patients. Men had significantly lower social functioning, more constipation, diarrhoea and sleep disturbance compared to the general male population. There was no significant difference in HRQoL domains between female patients and the general female population. A follow-up (FU) period longer than 37 months since surgery was associated with significantly improved physical- and role-functioning, less fatigue and fewer problems with the urostoma, compared to a shorter FU time. Conclusion: This study found a high global QoL score after radical cystectomy, comparable with the general Norwegian population. Symptoms seem to improve over time. Difference in HRQoL outcomes between men and woman in the study population was comparable with the difference found in the general population.
Differential Expression and Function of Bicellular Tight Junctions in Skin and Oral Wound Healing

Bicellular tight junctions are multiprotein complexes that are required for maintenance of barrier function and fence function in epithelial tissues. Wound healing in the oral cavity leads to minimal scar formation compared to the skin, and the precise mechanisms for this regenerative response remain to be elucidated. We hypothesized that oral and skin tissues express a different tight junction repertoire both at baseline and during the wound healing response, and that these molecules may be critical to the differential repair between the two tissues. We re-analyzed a mouse skin and palate epithelium microarray dataset to identify the tight junction repertoire of these tissue types. We then re-analyzed a skin and tongue wound healing microarray dataset to see how expression levels of tight junction genes change over time in response to injury. We performed in vitro scratch assays on human oral and skin keratinocyte cell lines to assay for tight junction expression over time, tight junction expression in response to lipopolysaccharide and histamine treatment, and the effects of siRNA knockdown of claudin 1 or occludin on migration and proliferation. Our data showed that oral and skin epithelium expressed different tight junction genes at baseline and during the wound healing response. Knockdown of claudin 1 or occludin led to changes in proliferation and migration in human skin keratinocytes but not oral keratinocytes. Furthermore, we also showed that skin keratinocytes were more permeable than oral keratinocytes upon histamine treatment. In conclusion, this study highlights a specific subset of functional tight junction genes that are differentially expressed between the oral and skin tissues, which may contribute to the mechanisms leading to distinct healing phenotypes in response to injury in the two tissues.
Additional hypotheses about why COVID‐19 is milder in children than adults

We read with great interest the editorial by Brodin discussing why COVID-19 appears to be so mild in children (1). In particular, the author discussed the potential theories that could explain why children have a lower incidence and milder clinical manifestations than adults. However, we feel it is important to present some other additional hypotheses in order to address all the potential theories.
Detection of virus-neutralising antibodies and associated factors against rabies in the vaccinated household dogs of Kathmandu Valley, Nepal

Background Rabies is a vaccine-preventable neglected tropical viral zoonosis. It occurs worldwide, creating a very heavy burden in many developing countries, including Nepal. Dogs are the principle vector for the transmission of this disease in urban areas. Vaccination is the most important preventive measure in areas where dogs are the principle source of infection. This study was conducted with the aim of detecting virus-neutralising antibodies and associated factors against rabies in vaccinated household dogs of Kathmandu valley. Methods Blood samples were collected from 110 vaccinated pet dogs in Kathmandu, Bhaktapur, and Lalitpur districts of Nepal. The samples were taken to the laboratory of the National Zoonosis and Food Hygiene Research Center where serum was separated. An indirect immune-enzymatic assay (PlateliaTM Rabies II kit ad usum Veterinarium, Biorad, China) was used for the detection of rabies virus anti-glycoprotein antibodies in the dog serum samples following the manufacturer’s recommendations and instructions. Optical density values for unknown samples were compared with the positive sera titers in quantification tests obtained after a direct reading on the standard curve. Results were expressed as equivalent units per ml (EU/ml). Findings Of the total samples, 89.09% exceeded the required seroconversion level (≥ 0.5 EU/ml); another 9.09% did not reach the seroconversion level (0.125–0.5 EU/ml); and 1.81% had undetectable seroconversion levels (<0.125 EU/ml) suggesting that the animal had not seroconverted according to the PLATELIA™ RABIES II test. Only one factor, the condition under which the dog was kept, was significantly associated with the antibody titer level. No association was found for any of the other factors included in the study. Interpretation Vaccination is the most effective measure for prevention and control of rabies. The locally manufactured brand of vaccine, which is available in Nepal, is potent enough to generate a sufficient amount of protective antibodies, equal to international brands.
Providing the Evidence for Managing Depression in Pregnancy

Pregnancy is a time of physical and emotional vulnerability, which can potentially lead to or exacerbate depression. Sadly, suicide is a leading cause of death in both high- and low-income countries.1,2 Although psychological therapies are effective and may be sufficient treatment for depression in pregnancy, for some women, antidepressant treatment may be required. Research also suggests that when women abruptly cease antidepressants in pregnancy, suicidal ideation may increase.3 Clinicians rely on research to accurately help patients weigh the risks and benefits of treatment options for depression that may save lives. For many women, the potential longer-term impacts on child outcomes are key deciding factors in whether to initiate or continue a specific type of antidepressant treatment.4,5 In a study … Address correspondence to Megan Galbally, MBBS, MPM, FRANZCP, PhD, College of Science, Health, Education, and Engineering, Murdoch University, 90 South Street, Murdoch, Western Australia, Australia. E-mail: m.galbally{at}murdoch.edu. au
Human Cytomegalovirus Congenital (cCMV) Infection Following Primary and Nonprimary Maternal Infection: Perspectives of Prevention through Vaccine Development

Congenital cytomegalovirus (cCMV) might occur as a result of the human cytomegalovirus (HCMV) primary (PI) or nonprimary infection (NPI) in pregnant women. Immune correlates of protection against cCMV have been partly identified only for PI. Following either PI or NPI, HCMV strains undergo latency. From a diagnostic standpoint, while the serological criteria for the diagnosis of PI are well-established, those for the diagnosis of NPI are still incomplete. Thus far, a recombinant gB subunit vaccine has provided the best results in terms of partial protection. This partial efficacy was hypothetically attributed to the post-fusion instead of the pre-fusion conformation of the gB present in the vaccine. Future efforts should be addressed to verify whether a new recombinant gB pre-fusion vaccine would provide better results in terms of prevention of both PI and NPI. It is still a matter of debate whether human hyperimmune globulin are able to protect from HCMV vertical transmission. In conclusion, the development of an HCMV vaccine that would prevent a significant portion of PI would be a major step forward in the development of a vaccine for both PI and NPI.
UTE T2* mapping of tendinopathic patellar tendons: an MRI reproducibility study

Background There is currently a lack of imaging modalities that can be used as a sensitive measure in tendinopathy. Recent findings suggest the applicability of ultra-short echo time (UTE) magnetic resonance imaging (MRI) T2* mapping in tendons, but the reproducibility remains unknown. Purpose To evaluate test–retest reproducibility of UTE MRI T2* mapping of tendinopathic patellar tendons and to evaluate the intra- and inter-observer reproducibility of the measurement. Material and Methods Fifteen patients with chronic patellar tendinopathy were evaluated with UTE MRI twice in a 3.0-T scanner on the same day. Manual segmentation of the patellar tendon was performed by two blinded investigators and automated T2*map reconstruction was performed in custom-made software. Results There was a significant and numerically small difference in test–retest T2* values (T2*meandiff = 0.06 ± 0.07 ms ≈ 3.7%; P = 0.006) with an ICC = 0.91 (95% confidence interval [CI] 0.58–0.98; typical error of 3.0%). The intra- and inter-observer reproducibility showed no significant bias (P = 0.493 and P = 0.052), and generally substantial reproducibility was demonstrated for T2* (intra-observer ICC = 0.99; 95% CI 0.98–1.00 and inter-observer ICC = 0.99; 95% CI 0.96–1.00, and typical error 1.3% and 1.3%, respectively). Conclusion These data demonstrate a small bias between repeated measurements for UTE T2*, but with a very low associated mean difference (3.7%) between the two tests. The high ICC values and low typical error % demonstrate reproducibility of repeated T2*-mapping sessions. Further, the method showed substantial intra- and inter-observer reproducibility for T2* values proving feasibility for use of UTE T2* mapping in research and clinical practice.
Safety and Efficacy of Apatinib Monotherapy for Unresectable, Metastatic Esophageal Cancer: A Single-Arm, Open-Label, Phase II Study.

LESSONS LEARNED Patient compliance with the oral dosage treatment was good, with no need for hospitalization. Patients with tracheal and esophageal fistulas can take crushed apatinib by nutrient tube, with the same bioavailability and efficacy. Apatinib may be an effective and safe second- or further-line treatment for advanced esophageal cancer. BACKGROUND Apatinib is an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR2), which is thought to play a role in esophageal cancer progression. Our goal was to evaluate the efficacy and safety of apatinib in patients with unresectable esophageal cancer and to examine whether VEGFR2 expression influenced the clinical response. METHODS This single-arm, open-label, investigator-initiated phase II study enrolled patients with advanced squamous cell carcinoma (SCC) or adenocarcinoma of the esophagus or esophagogastric junction who were admitted to Tianjin Medical University Cancer Institute and Hospital between August 2017 and January 2019. Apatinib monotherapy (500 mg/day) was given orally or via an enteral tube until disease progression, unacceptable toxicity, withdrawal, or death. Patients were followed until treatment was discontinued or death. The main endpoints were tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs). RESULTS Among 32 patients screened for inclusion, 30 were included in the safety and survival analyses (i.e., received apatinib), and 26 were included in the efficacy analysis (at least one imaging follow-up). Median follow-up time and exposure to apatinib were 5.34 months and 72 days, respectively. Among 26 patients included in the efficacy analysis, 2 had a partial response (PR; 7.7%) and 14 had stable disease (SD; 53.8%). The overall response rate (ORR) was 7.7%, and the disease control rate (DCR) was 61.5%. Median PFS and OS were 4.63 months (95% confidence interval, 2.11-7.16 months) and 6.57 months (4.90 months to not estimable), respectively. Fifteen patients (50.0%) experienced treatment-related AEs, most commonly hypertension (26.7%), diarrhea (20.0%), and hand-foot-skin reaction (10.0%). No patients had grade ≥ 4 treatment-related AEs. CONCLUSION Apatinib was effective as second- or further-line treatment for advanced esophageal cancer.