Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state.

Myc oncoproteins directly regulate transcription by binding to target genes, yet this only explains a fraction of the genes affected by Myc. mRNA turnover is controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs) found within many transcripts. Analyses of precancerous and malignant Myc-expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED) genes and select AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also operational during B lymphopoiesis and IL7 signaling. Importantly, TTP suppression is a hallmark of cancers with MYC involvement, and restoring TTP impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant state. Further, there is a selection for TTP loss in malignancy; thus, TTP functions as a tumor suppressor. Finally, Myc/TTP-directed control of select cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc targets AUBPs to regulate ARED genes that control tumorigenesis.

Bile acid profile associated with CSF and PET biomarkers in Alzheimer's disease.

BACKGROUND: Recent studies have shown that gut microbiota can affect the development of Alzheimer's disease (AD) through various mechanisms. Bile acids (BAs), which are the final byproducts of cholesterol metabolism created through both the human body and gut microbiome, appear to be influenced by gut microbiota and may impact AD pathological characteristics such as the accumulation of tau and amyloid-ß. We aimed to investigate the associations between various serum BAs and CSF biomarkers (including Aß, total tau, and p-tau). Additionally, we sought to examine the longitudinal changes in brain Aß and tau through PET imaging in relation to BAs profile. METHODS: The data of 828 subjects including 491 diagnosed with mild cognitive impairment (MCI), 119 patients diagnosed with AD, and 267 cognitively normal (CN) participants were obtained from ADNI. The baseline and longitudinal [18F] florbetapir and [18F] flortaucipir PET standard uptake value ratios (SUVR) measures were obtained to assess the accumulation of tau and Aß. Moreover, baseline levels of serum BAs and CSF Aß1-42, tau, and p-tau were used. RESULTS: After FDR correction we observed that five BAs level and relevant calculated ratios were associated with CSF p-tau and tau, three with CSF Aß1-42. Furthermore, three BAs level and relevant calculated ratios were associated with the tau-PET rate of change, and two with the Aß rate of change. CONCLUSION: The findings from our study suggest a correlation between altered profiles of BAs and CSF and imaging biomarkers associated with AD. These results provide supporting evidence for the link between the gut microbiome and the pathological features of AD.

Stereotactic radiosurgery in the management of skull base chordomas: a comprehensive systematic review and meta-analysis.

OBJECTIVE: Chordoma is a primary bone tumor with limited literature on its management because of its rarity. Resection, while considered the first-line treatment, does not always provide adequate tumor control. In this systematic review, the authors aimed to provide comprehensive insights by managing these tumors with stereotactic radiosurgery (SRS). METHODS: A systematic review was conducted according to PRISMA guidelines using the PubMed, Scopus, Web of Science, Embase, and Cochrane Library databases. Search terms included chordoma and radiosurgery and their equivalent terms. Data on baseline characteristics, SRS details, and outcomes were extracted. The Joanna Briggs Institute checklist was used to assess risk of bias. A meta-analysis was performed on relevant variables. RESULTS: A total of 33 eligible studies encompassing 714 patients with skull base chordomas were included. Most studies had a low risk of bias. Patients, predominantly male (57.37%) with a mean age of 46.54 years, exhibited a conventional chordoma subtype (74.77%) and primary lesions (77.91%), mainly in the clivus (98.04%). The mean lesion volume was 13.49 cm3, and 96.68% of patients had undergone prior surgical attempts. Gamma Knife radiosurgery (88.76%) was the predominant SRS method. Radiologically, 27.19% of patients experienced tumor regression, while 55.02% showed no signs of disease progression at the latest follow-up. Progression occurred after a mean of 48.02 months. Symptom improvement was noted in 27.98% of patients. Radiosurgery was associated with a relatively low overall adverse event rate (11.94%), mainly cranial nerve deficits (8.72%). Meta-regression revealed that age and primary lesion type influenced symptom improvement, while factors like extent of resection, radiotherapy, and SRS type affected adverse event rates. CONCLUSIONS: This systematic review provides evidence on the safety and effectiveness of radiosurgery in the management of skull base chordomas. Local tumor control was achieved in the majority of patients treated with SRS. Various baseline characteristics and SRS features have been analyzed to identify modifying factors for each outcome to provide a framework for informed decision-making when managing these patients.

Stereotactic radiosurgery with versus without embolization for intracranial dural arteriovenous fistulas: a systematic review and meta-analysis.

OBJECTIVE: Stereotactic radiosurgery (SRS) has been established as a safe and alternative treatment for dural arteriovenous fistulas (dAVFs). While embolization alone is the most commonly used modality for the treatment of dAVFs, the adjunctive use of embolization with SRS, with the growing use of SRS, has gained increasing interest in the past few years. However, the relative efficacy and safety of SRS combined with embolization versus SRS alone for dAVFs remains uncertain. Hence, this systematic review aimed to evaluate the efficacy of SRS with adjunctive embolization for intracranial dAVFs. METHODS: A systematic review and meta-analysis was conducted by searching electronic databases, including PubMed, Embase, and the Cochrane Library, up to August 2023. All studies evaluating the utilization of adjunctive embolization and SRS for dAVFs were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was conducted on the suitable outcomes. RESULTS: Eighteen studies involving 715 patients were included. The mean age of the participants in the study was 64.30 years in the adjunctive embolization group and 60.51 years in the SRS-alone group. In the adjunctive embolization group 41.3% of patients were female, compared with 47.1% in the SRS-only group. The dAVF obliteration rates were 64.7% and 65.7% in the adjunctive embolization and SRS-alone groups, respectively. These obliteration rates were comparable between the two groups (p = 0.96), as were the symptom improvement rates (p = 0.35). Adverse events were rare, and were more commonly associated with the adjunctive embolization procedure, although further causal analysis was not possible. CONCLUSIONS: This study provides evidence that adjunctive embolization plus SRS provides similar obliteration and symptom improvement rates compared with SRS alone, with both having very limited SRS-related adverse events. Considering the added burden and adverse events of additional endovascular treatment, the authors recommend embolization be reserved for more complex dAVFs or when embolization can potentially be curative alone or provide more rapid symptomatic relief or protection during the radiosurgical latency period.

Robotic assisted Total Knee Arthroplasty (TKA) is not associated with increased patient satisfaction: a systematic review and meta-analysis.

PURPOSE: Total knee arthroplasty (TKA) is a common orthopedic surgery, yet postoperative dissatisfaction persists in around 20% of cases. Robotic total knee arthroplasty (rTKA) promises enhanced precision, but its impact on patient satisfaction compared to conventional TKA remains controversial (cTKA). This systematic review aims to evaluate patient satisfaction post-rTKA and compare outcomes with cTKA. METHODS: Papers from the following databases were identified and reviewed: PubMed, Scopus, Web of Science, and the Cochrane Online Library, using keywords like "Knee replacement," "Total knee arthroplasty," "Robotic," and "Patient satisfaction." Extracted data included patient satisfaction measures, Knee Society Score, Oxford Knee Score, Forgotten Joint Score, SF-36, HSS, and KOOS. Statistical analysis, including odds ratio and 95% CI was performed using R software. Heterogeneity was assessed using Cochrane's Q test. RESULTS: The systematic review included 17 articles, involving 1148 patients (571 in the rTKA group and 577 in the cTKA group) assessing patient satisfaction following rTKA. An analysis of proportions reveals rTKA satisfaction rate was 95%, while for cTKA, it was 91%. A meta-analysis comparing rTKA and cTKA found no statistically significant difference in patient satisfaction. Additionally, various patient-reported outcome measures (PROMs) were examined, showing mixed results across different studies and follow-up periods. CONCLUSIONS: The results of this study found no difference in patient satisfaction outcomes in the short to mid-term for rTKA compared to conventional methods. This study does not assert superiority for the robotic approach, highlighting the need for careful consideration of various factors influencing outcomes in knee arthroplasty.

MRI features and disability in multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: In this systematic review and meta-analysis, we aimed to investigate the correlation between disability in patients with Multiple sclerosis (MS) measured by the Expanded Disability Status Scale (EDSS) and brain Magnetic Resonance Imaging (MRI) features to provide reliable results on which characteristics in the MRI can predict disability and prognosis of the disease. METHODS: A systematic literature search was performed using three databases including PubMed, Scopus, and Web of Science. The selected peer-reviewed studies must report a correlation between EDSS scores and MRI features. The correlation coefficients of included studies were converted to the Fisher's z scale, and the results were pooled. RESULTS: Overall, 105 studies A total of 16,613 patients with MS entered our study. We found no significant correlation between total brain volume and EDSS assessment (95 % CI: -0.37 to 0.08; z-score: -0.15). We examined the potential correlation between the volume of T1 and T2 lesions and the level of disability. A positive significant correlation was found (95 % CI: 0.19 to 0.43; z-score: 0.31), (95 % CI: 0.17 to 0.33; z-score: 0.25). We observed a significant correlation between white matter volume and EDSS score in patients with MS (95 % CI: -0.37 to -0.03; z-score: -0.21). Moreover, there was a significant negative correlation between gray matter volume and disability (95 % CI: -0.025 to -0.07; z-score: -0.16). CONCLUSION: In conclusion, this systematic review and meta-analysis revealed that disability in patients with MS is linked to extensive changes in different brain regions, encompassing gray and white matter, as well as T1 and T2 weighted MRI lesions.

Weight Change and the Risk of Micro and Macro Vascular Complications of Diabetes: A Systematic Review.

Type 2 diabetes mellitus (T2DM) is a metabolic disease that can be a significant cause of cardiovascular disease (CVD), leading to macrovascular and microvascular diseases. Many researchers around the world have investigated the effects of weight change on micro and macro CVD in patients with T2DM. This study aimed to investigate the effect of weight change (weight gain and loss) on microvascular and macrovascular complications in patients with T2DM. We searched PubMed, Scopus and Google Scholar from the database until January 2023. We screened the title, abstract, and full text of articles, and after quality assessment, we extracted data from interrelated ones into this systematic review. Reviewing the results of 11 cohort studies with 219,839 individuals (T2DM patients) showed that weight loss caused an increase in the mortality rate in diabetic patients, while weight gain after diabetes diagnosis increased the risk of CVD, chronic kidney disease (CKD), microvascular disease, stroke and mortality. It should be noted that severe body weight variability increases the mortality rate and the risk of microvascular disease. Unlike other studies, one study showed that more than 5% weight gain positively affected CVD and coronary heart disease in T2DM patients. Generally, weight change in patients with T2DM is an essential sign of cardiovascular complications. According to our findings, the risk of cardiovascular complications in patients with weight loss is seen to be higher than in patients with weight gain. In regular patients with body mass index (BMI), stable weight in a healthy range is reported to decrease the risk of CVD.

Prophylactic cranial irradiation effect on survival in patients with small cell lung cancer: a comprehensive systematic review and meta-analysis.

OBJECTIVE: Prophylactic cranial irradiation (PCI) is a companion treatment option for small cell lung cancer (SCLC) patients. However, its efficacy and associated risk factors have not been clearly defined. In this study, the authors aimed to systematically assess the effectiveness and role of PCI in the treatment plan of SCLC. METHODS: The PubMed, Scopus, Web of Science, and Cochrane databases were searched using the following key terms and their equivalents: "brain," "radiotherapy," "metastases," "prophylactic," and "small cell lung cancer." Studies comparing overall survival (OS), progression-free survival (PFS), brain metastasis-free survival (BMFS), and incidence of brain metastases between patients receiving PCI and those not receiving it were considered eligible. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies-of Interventions (ROBINS-I) tool. Meta-analysis was conducted on the mentioned outcomes with subgrouping based on different factors. RESULTS: The authors identified 74 studies published between 1983 and 2022 with 31,551 SCLC patients, of whom 26.7% received PCI. The studies were a mix of prospective randomized and retrospective observational studies. Patients with limited-stage disease receiving PCI had better OS, PFS, and BMFS than those not receiving PCI. Patients receiving PCI also had significantly longer OS times and developed brain metastases significantly later. However, findings regarding extensive-stage SCLC were not as promising. CONCLUSIONS: PCI is an effective option for limited-stage SCLC patients. It improves OS and PFS, delays brain metastases, and reduces the incidence of brain metastases. However, it might not benefit patients with extensive-stage SCLC under adequate follow-up with MRI surveillance. Finally, the heterogeneity of the included studies and publication bias were the main limitations of this study.

Esophageal perforation etiology, outcome, and the role of surgical management - an 18-year experience of surgical cases in a referral center.

INTRODUCTION: Esophageal perforation is a surgical emergency with a high rate of morbidity and mortality. Its poor prognosis is mainly associated with previous patient-specific comorbidities and a lack of timely diagnosis and treatment. The objective of this study was to investigate the etiological factors and different surgical methods of treatment with consideration of mortality rate and comorbidities. METHOD: The present cross-sectional study was conducted on patients who underwent surgical intervention due to esophageal injury from 2002 to 2019 (18 years). Demographic and clinical characteristics along with performed surgical interventions were evaluated accordingly. RESULTS: In this study, 69 patients with a mean age of 38.8 years were evaluated, of which 45 (65.2%) cases were men. In terms of location of the perforation, the thoracic portion of the esophagus followed by the cervical and abdominal esophagus were more frequently injured with a rate of 32 (46.4%), 30 (43.5%), and 19 (27.5%) cases, respectively. Accordingly, foreign body ingestion followed by penetrating injuries were the most common causative agents leading to esophageal perforation. CONCLUSION: Obtaining the desired results from the treatment of this condition depends on factors such as patients' previous comorbidities, cause of the rupture, the location of the esophageal damage, and delay in the start of treatment. Since there is no single gold standard treatment strategy, each patient should be individually evaluated.

The effect of suture techniques on the outcome of tracheal reconstruction: An observational study and review of literature.

BACKGROUND: Tracheal resection and anastomosis surgery is a safe operation and is used to treat various benign and malignant diseases of the trachea. However, tracheal stenosis is among the main anastomotic complications following this procedure. Surgeons use both the continuous and the interrupted suture techniques for tracheal anastomosis, but contradicting results in each technique's complications have been reported in various studies. In this study, we aimed to compare the outcome of these two different suture techniques and a relevant literature review. METHODS: Surgical records during a period of 15 years (2005-2019) were screened for tracheal reconstruction surgery in affiliated hospitals of Shiraz University of Medical Sciences, Shiraz, Iran. A total of 82 patients were evaluated based on surgical and suture features, along with their follow-up bronchoscopy for anastomotic complications. RESULTS: Post-operational subclinical restenosis occurred in 8 (15.3%) out of 52 and 10 (33.3%) of 30 patients who underwent continuous and interrupted suturing techniques, respectively. Also, 6 (20%) patients in the interrupted group developed symptomatic restenosis, while in the continuous group, only one patient was clinically symptomatic. The patients with continuous suture technique had a shorter surgery time than patients whose interrupted technique was used (P < 0.001). CONCLUSIONS: Based on our results, we conclude that restenosis is significantly reduced when the continuous technique is applied for tracheal anastomosis; However, the results are contradicting in relevant literature and due to the retrospective nature of our study, further human studies and clinical trials are warranted.

Lung cancer registry and monitoring: Feasibility study and application (fars lung cancer registry project).

Background: Lung cancer (LC) is the second most common and deadliest cancer in the world. Despite the control of the progressive course of LC in developed countries, studies indicate an increase in the incidence of the disease in developing countries. We designed a stepwise approach-based surveillance system for registering LC in our region (fars lung cancer registry "FaLCaRe" Project). Materials and Methods: A questionnaire was designed and agreed upon by the steering committee using the Delphi method. Variables in nine fields were divided into three groups based on their importance: core, expanded core, and optional. The web-based data bank software was designed. The informative site about LC and team services was designed and launched for professional and community (www.falcare.org) educational purposes. Results: 545 variables in nine fields were designed (20 core variables). Primary data of 39 LC patients (24 men and 15 women) with a mean age of 62 years were analyzed. Twenty-six patients had a history of smoking. Moreover, 39% and 26% of patients had a history of hookah smoking and opium use, respectively. Adenocarcinoma was the most prevalent pathologic findings in cases. More than 80% of patients were diagnosed in stages 3 and 4 of cancer. Conclusion: FaLCaRe Project with the capabilities seen in it can be used as a model for national LC registration. With continuous valid data registry about LC, it is possible to make decisions at the national level for control and management its consequences while drawing the natural history of the LC.

The association between helicobacter pylori infection and erosive gastroesophageal reflux disease; a cross-sectional study.

BACKGROUND: The association between H. pylori (Helicobacter pylori) infection and gastroesophageal reflux disease (GERD) is a complex and confusing subject. The aim of this study was to evaluate the association between helicobacter pylori infection and erosive gastroesophageal reflux disease. METHOD: In a cross-sectional study, all patients referred for endoscopy due to dyspepsia were enrolled. The diagnosis of erosive GERD was made by endoscopy. Patients with normal esophagus were selected as comparison group. Random gastric biopsies were taken from all participants to diagnose H. pylori infection. RESULT: In total, 1916 patients were included in this study, of whom 45.6% had GERD. The mean age (SD) was 42.95 (16.32). Overall, 1442 (75.3%) patients were positive for H. pylori infection. The frequency of H. pylori infection in mild GERD patients was higher than the severe GERD, but this difference was not significant (P = 0.214). Except for sociodemographic status (P < 0.001), other variables including gender, age, ethnicity, body mass index (BMI), smoking, and presence of hiatus hernia in patients had no significant association with the frequency of H. pylori infection. According to Robust Poisson regression models analysis, the association of H. pylori (PR 1.026; 95% CI 0.990-1.064; P = 0.158) and sociodemographic status were not significantly different between the two groups. But smoking, increased BMI, older age, presence of hiatus hernia, and peptic ulcer diseases were significantly associated with GERD compared with the non-GERD group. CONCLUSION: In our results, there was no association between H. pylori infection and erosive GERD. Further studies are recommended.

Evaluation of the appropriate use of chest CT-Scans in the diagnosis of hospitalized patients in shiraz teaching hospitals, Southern Iran.

PURPOSE: During recent years, overuse of medical imaging especially computed tomography has become a serious concern. We evaluated the suitable usage of chest computed tomography (CT)-scan, in patients hospitalized in emergency and medical wards of two teaching hospitals of Shiraz University of Medical Science. METHODS: Medical records of 216 patients admitted in two major teaching hospitals (Namazi and Shahid Faghihi), who had undergone chest radiography and at least one type of chest CT were investigated. The clinical and paraclinical manifestations were independently presented to three pulmonologists and their opinion regarding the necessity and type of CT prescription were documented. Also, the patient's history was presented to an expert chest radiologist and asked to rate the appropriateness of chest CT according to American colleague of radiologist (ACR) criteria. RESULTS: In 127 cases (59%), at least 2 out of 3 pulmonologists had the same opinion on the necessity of performing CT scan regardless of CT scan type, in 89 cases (41%) the same CT type and in 38 (17.5%) cases other CT type was supposed. Based on ACR criteria, of total prescribed CTs, 49.5% were "usually not appropriate" and 31.5% of cases were "usually appropriate". Among 109 pulmonary CT angiography, 54 (49.5%) was usually not appropriate base on ACR criteria, which was the most frequent inappropriate requested CT type. CONCLUSION: Considering the high rates of inappropriate utilization of chest CT scan in our teaching hospitals, implementation of the standard guideline at a different level and consulting with a pulmonologist, may prevent unnecessary chest CTs prescription and reduce harm to patients and the health system.

COVID-19 infection among healthcare workers: a cross-sectional study in southwest Iran.

OBJECTIVE: With the novel coronavirus pandemic, the impact on the healthcare system and workers cannot be overlooked. However, studies on the infection status of medical personnel are still lacking. It is imperative to ensure the safety of health-care workers (HCWs) not only to safeguard continuous patient care but also to ensure they do not transmit the virus, therefore evaluation of infection rates in these groups are indicated. METHODS: Demographic and clinical data regarding infected cases among HCWs of Fars, Iran with positive SARS-CoV-2 PCR tests were obtained from 10th March to 17th May 2020. RESULTS: Our data demonstrated a rate of 5.62% (273 out of 4854 cases) infection among HCW, with a mean age of 35 years and a dominance of female cases (146 cases: 53.5%). The majority of infected cases were among nurses (51.3%), while the most case infection rate (CIR) was among physicians (27 positive cases out of 842 performed test (3.2%)). Also, the highest rate of infection was in the emergency rooms (30.6%). Also, 35.5% of the patients were asymptomatic and the most frequent clinical features among symptomatic patients were myalgia (46%) and cough (45.5%). Although 5.5% were admitted to hospitals, there were no reports of ICU admission. Furthermore, 10.3% of the cases reported transmitting the infection to family and friends. Regarding safety precautions, 1.6% didn't wear masks and 18.7% didn't use gloves in work environments. CONCLUSION: HCWs are among the highest groups at risk of infection during the COVID-19 pandemic; therefore, evaluating infection rates and associated features is necessary to improve and adjust protective measures of these vulnerable, yet highly essential group.

Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: a triple-blinded randomized controlled trial.

BACKGROUND: Although almost a year has passed since the Coronavirus disease 2019 (COVID-19) outbreak and promising reports of vaccines have been presented, we still have a long way until these measures are available for all. Furthermore, the most appropriate corticosteroid and dose in the treatment of COVID-19 have remained uncertain. We conducted a study to assess the effectiveness of methylprednisolone treatment versus dexamethasone for hospitalized COVID-19 patients. METHODS: In this prospective triple-blinded randomized controlled trial, we enrolled 86 hospitalized COVID-19 patients from August to November 2020, in Shiraz, Iran. The patients were randomly allocated into two groups to receive either methylprednisolone (2 mg/kg/day; intervention group) or dexamethasone (6 mg/day; control group). Data were assessed based on a 9-point WHO ordinal scale extending from uninfected (point 0) to death (point 8). RESULTS: There were no significant differences between the groups on admission. However, the intervention group demonstrated significantly better clinical status compared to the control group at day 5 (4.02 vs. 5.21, p = 0.002) and day 10 (2.90 vs. 4.71, p = 0.001) of admission. There was also a significant difference in the overall mean score between the intervention group and the control group, (3.909 vs. 4.873 respectively, p = 0.004). The mean length of hospital stay was 7.43 ± 3.64 and 10.52 ± 5.47 days in the intervention and control groups, respectively (p = 0.015). The need for a ventilator was significantly lower in the intervention group than in the control group (18.2% vs 38.1% p = 0.040). CONCLUSION: In hospitalized hypoxic COVID-19 patients, methylprednisolone demonstrated better results compared to dexamethasone. TRIAL REGISTRATION: The trial was registered with IRCT.IR (08/04/2020-No. IRCT20200204046369N1 ).

Correction to: Genomic measures of inbreeding coefficients and genome-wide scan for runs of homozygosity islands in Iranian river buffalo, Bubalus bubalis.

Following publication of the original article [1], the authors flagged that the article had published with the author 'Ali Jalil Sarghale' erroneously omitted from the author list.

Genomic measures of inbreeding coefficients and genome-wide scan for runs of homozygosity islands in Iranian river buffalo, Bubalus bubalis.

BACKGROUND: Consecutive homozygous fragments of a genome inherited by offspring from a common ancestor are known as runs of homozygosity (ROH). ROH can be used to calculate genomic inbreeding and to identify genomic regions that are potentially under historical selection pressure. The dataset of our study consisted of 254 Azeri (AZ) and 115 Khuzestani (KHZ) river buffalo genotyped for ~ 65,000 SNPs for the following two purposes: 1) to estimate and compare inbreeding calculated using ROH (FROH), excess of homozygosity (FHOM), correlation between uniting gametes (FUNI), and diagonal elements of the genomic relationship matrix (FGRM); 2) to identify frequently occurring ROH (i.e. ROH islands) for our selection signature and gene enrichment studies. RESULTS: In this study, 9102 ROH were identified, with an average number of 21.2 ± 13.1 and 33.2 ± 15.9 segments per animal in AZ and KHZ breeds, respectively. On average in AZ, 4.35% (108.8 ± 120.3 Mb), and in KHZ, 5.96% (149.1 ± 107.7 Mb) of the genome was autozygous. The estimated inbreeding values based on FHOM, FUNI and FGRM were higher in AZ than they were in KHZ, which was in contrast to the FROH estimates. We identified 11 ROH islands (four in AZ and seven in KHZ). In the KHZ breed, the genes located in ROH islands were enriched for multiple Gene Ontology (GO) terms (P ≤ 0.05). The genes located in ROH islands were associated with diverse biological functions and traits such as body size and muscle development (BMP2), immune response (CYP27B1), milk production and components (MARS, ADRA1A, and KCTD16), coat colour and pigmentation (PMEL and MYO1A), reproductive traits (INHBC, INHBE, STAT6 and PCNA), and bone development (SUOX). CONCLUSION: The calculated FROH was in line with expected higher inbreeding in KHZ than in AZ because of the smaller effective population size of KHZ. Thus, we find that FROH can be used as a robust estimate of genomic inbreeding. Further, the majority of ROH peaks were overlapped with or in close proximity to the previously reported genomic regions with signatures of selection. This tells us that it is likely that the genes in the ROH islands have been subject to artificial or natural selection.

Acute portal vein thrombosis secondary to COVID-19: a case report.

BACKGROUND: COVID-19 pneumonia exhibits several extra-pulmonary complications. CASE PRESENTATION: A 23-year old, asthmatic male with coronavirus pneumonia developed with generalized, acute abdominal pain. Further evaluations revealed a mild ascites and portal vein thrombosis although the patient received proper anticoagulation therapy. Routine lab data regarding the secondary causes of portal vein thrombosis were normal. CONCLUSION: We speculated that the underlying cause of portal vein thrombosis in our case was coronaviruses. Therefore, clinicians should always consider thrombosis and other hypercoagulable diseases in patients with COVID-19.

Spatial mapping of thymic stromal microenvironments reveals unique features influencing T lymphoid differentiation.

Interaction of hematopoietic progenitors with the thymic microenvironment induces them to proliferate, adopt the T lineage fate, and asymmetrically diverge into multiple functional lineages. Progenitors at various developmental stages are stratified within the thymus, implying that the corresponding microenvironments provide distinct sets of signals to progenitors migrating between them. These differences remain largely undefined. Here we used physical and computational approaches to generate a comprehensive spatial map of stromal gene expression in the thymus. Although most stromal regions were characterized by a unique gene expression signature, the central cortex lacked distinctive features. Instead, a key function of this region appears to be the sequestration of unique microenvironments found at the cortical extremities, thus modulating the relative proximity of progenitors moving between them. Our findings compel reexamination of how cell migration, lineage specification, and proliferation are controlled by thymic architecture and provide an in-depth resource for global characterization of this control.

Agonist antibody that induces human malignant cells to kill one another.

An attractive, but as yet generally unrealized, approach to cancer therapy concerns discovering agents that change the state of differentiation of the cancer cells. Recently, we discovered a phenomenon that we call "receptor pleiotropism" in which agonist antibodies against known receptors induce cell fates that are very different from those induced by the natural agonist to the same receptor. Here, we show that one can take advantage of this phenomenon to convert acute myeloblastic leukemic cells into natural killer cells. Upon induction with the antibody, these leukemic cells enter into a differentiation cascade in which as many as 80% of the starting leukemic cells can be differentiated. The antibody-induced killer cells make large amounts of perforin, IFN-γ, and granzyme B and attack and kill other members of the leukemic cell population. Importantly, induction of killer cells is confined to transformed cells, in that normal bone marrow cells are not induced to form killer cells. Thus, it seems possible to use agonist antibodies to change the differentiation state of cancer cells into those that attack and kill other members of the malignant clone from which they originate.