ChromaX: a fast and scalable breeding program simulator.

SUMMARY: ChromaX is a Python library that enables the simulation of genetic recombination, genomic estimated breeding value calculations, and selection processes. By utilizing GPU processing, it can perform these simulations up to two orders of magnitude faster than existing tools with standard hardware. This offers breeders and scientists new opportunities to simulate genetic gain and optimize breeding schemes. AVAILABILITY AND IMPLEMENTATION: The documentation is available at https://chromax.readthedocs.io. The code is available at https://github.com/kora-labs/chromax.

Heart failure with reduced ejection fraction and chronic kidney disease: a focus on therapies and interventions.

In heart failure with reduced ejection fraction (HFrEF), the presence of concomitant chronic kidney disease (CKD) predicts poorer cardiovascular outcomes, more aggravated heart failure (HF) status, and higher mortality. Physicians might be reluctant to initiate life-saving anti-HF medications out of fear of worsening renal function and a higher incidence of adverse events. Moreover, international guidelines do not give clear recommendations on managing this subgroup of patients as well as advanced CKD was always an exclusion criterion in most major HF trials. Nevertheless, in this review, we will highlight several recent clinical trials and post-hoc analyses of major trials that showed the safety and efficacy of the different therapies in HFrEF patients with CKD, besides several small-scale cohorts that tested guideline-directed medical therapies in End Stage Kidney Disease (ESKD). Regarding interventions in this subgroup of patients, we will provide up-to-date data on implantable cardioverter defibrillators, cardiac resynchronization therapy, and coronary revascularization, in addition to mitral valve transcatheter edge-to-edge repair and implantable pulmonary artery pressure sensors.

Hidden intruder: Plasmacytoma causing uncontrolled epistaxis in an elderly patient.

Extramedullary plasmacytoma (EMP) is an uncommon tumor marked by the monoclonal growth of plasma cells without the characteristics of multiple myeloma. EMP represents 3% of all plasma cell tumors. An 89-year-old male patient with hypertension was admitted to our tertiary care hospital with uncontrolled unilateral epistaxis. After a year and a half of recurring epistaxis, the patient's bleeding became more frequent and could no longer be controlled with nasal packing. Angiofibroma was suspected as the initial differential diagnosis, and angiofibroma embolization was performed. The patient experienced difficulty swallowing and slurred speech and was diagnosed with an ischemic stroke. However, antiplatelet and tranexamic acid medications were contraindicated due to bleeding risks. The patient underwent functional endoscopic sinus surgery, and unexpectedly, histology results revealed a plasmacytoma. After surgery, the patient remained stable and was discharged for further management.

Sural flap reconstruction of lateral malleolus following undifferentiated pleomorphic sarcoma resection with 1-year follow-up.

We report a case of a 54-year-old female who presents with a gradually expanding mass at the right lateral malleolus. The diagnosis of undifferentiated pleomorphic sarcoma was made after a histopathological examination of the mass following a wide tumor excision. The defected soft tissue area was reconstructed using a local flap, reverse sural artery flap. Following the surgical management, multiple radiotherapy sessions were completed. The patient's follow-up result showed no signs of local recurrence or metastasis, and the wound was well-healed with no complications other than paresthesia in a small area at the posterolateral aspect of the ankle under the lateral malleolus. This case represents a rare form of malignant neoplasm and emphasizes the effectiveness and safety of the reverse sural artery flap reconstruction technique, especially in places where microsurgery is unavailable or when the patient's status does not allow for prolonged anesthesia.

Imaging reveals a fifth heart chamber: Diagnosing and treating a massive left atrial appendage aneurysm.

In this case report, a 33-year-old male with a history of smoking presented with recurrent palpitations and chest discomfort. Holter monitoring revealed atrial flutter, and imaging showed a giant left atrial appendage aneurysm. Due to the risk of arrhythmias and thromboembolic events, surgical resection was performed successfully. This case underscores the importance of considering uncommon structural cardiac abnormalities in the evaluation of arrhythmia symptoms in young patients.

Wandering Spleen Torsion: A Diagnostic Challenge.

Wandering spleen, or hypermobile spleen, arises from the elongation or maldevelopment of the spleen's suspensory ligaments. This condition is a rare clinical entity, primarily affecting children, with a higher prevalence among adult females in the active reproductive age group. Manifestations may include an asymptomatic abdominal mass or intermittent abdominal discomfort due to the torsion and subsequent spontaneous detorsion of the spleen. This case report details the presentation of a 14-year-old female initially misdiagnosed as having gastroenteritis who later experienced acute abdomen. Subsequent ultrasonography and computed tomography scan revealed splenic torsion, confirmed during exploratory laparotomy, which demonstrated an infarcted spleen. The definitive therapeutic intervention was a total splenectomy. This clinical entity should be taken into account in the differential diagnosis of acute abdominal pain in order to aid in early diagnosis and management. This could allow us to avoid splenectomy whenever possible and instead do splenopexy, especially in pediatric cases, as the spleen plays a crucial role in the reticuloendothelial system.

Engrailed-1 Promotes Pancreatic Cancer Metastasis.

Engrailed-1 (EN1) is a critical homeodomain transcription factor (TF) required for neuronal survival, and EN1 expression has been shown to promote aggressive forms of triple negative breast cancer. Here, it is reported that EN1 is aberrantly expressed in a subset of pancreatic ductal adenocarcinoma (PDA) patients with poor outcomes. EN1 predominantly repressed its target genes through direct binding to gene enhancers and promoters, implicating roles in the activation of MAPK pathways and the acquisition of mesenchymal cell properties. Gain- and loss-of-function experiments demonstrated that EN1 promoted PDA transformation and metastasis in vitro and in vivo. The findings nominate the targeting of EN1 and downstream pathways in aggressive PDA.

Impact of dapagliflozin on cardiac function following anterior myocardial infarction in non-diabetic patients - DACAMI (a randomized controlled clinical trial).

BACKGROUND: The role of Sodium-glucose co-transporter 2 inhibitors (SGLT2i) in heart failure is established. Early data also suggests their favorable role in patients with acute coronary syndromes, but more evidence is still needed. METHODS: In this dual center, double-blinded randomized controlled trial, non-diabetic patients (N = 100) who presented with anterior ST- elevation myocardial infarction (STEMI) & had undergone successful primary percutaneous coronary intervention, but their left ventricular ejection fraction was below 50%, were randomized to dapagliflozin 10 mg or a placebo once daily. The primary endpoint was a change in cardiac function assessed by N-terminal pro-Brain Natriuretic Peptide - NT-proBNP measured at baseline & 12 weeks post the cardiac event &/or echocardiographic parameters (left ventricular ejection fraction, left ventricular diastolic dimension & left ventricular mass index) assessed at baseline, 4-weeks & 12-weeks post the cardiac event. RESULTS: From October 2021 to April 2022, 100 patients were randomized. The mean drop of NT- proBNP in the study group was more significant compared to the control group by 10.17% (95% CI: -3.28-19.67, p-value 0.034). In addition, the decrease in the left ventricular mass index (LV mass index) was also significant in the study group compared to the control group by 11.46% (95% CI: -19.37 to -3.56, p-value 0.029). CONCLUSIONS: Dapagliflozin seems to have a role in preventing left ventricular dysfunction & maintaining cardiac function following anterior ST-elevation myocardial infarction. More Large-scale trials need to be done to confirm these findings further. This trial is locally registered at the National Heart Institute, Cairo - Egypt, and Faculty of Medicine, Ain Shams University, with reference numbers CTN1012021 & MS-07/2022, respectively. It is also registered retrospectively at the US National Institutes of Health (ClinicalTrial.gov) with identifier number: NCT05424315 - June 16th,2022.

Bilateral Dacryoadenitis As the First Presentation in an Undiagnosed Sarcoidosis Patient.

Sarcoidosis is an idiopathic multisystem disorder associated with hilar lymphadenopathy and noncaseating granulomas that can affect any organ. Ocular involvement is less common; however, sarcoidosis is a known cause of uveitis, dry eye, and conjunctival nodules. We report a case of a 36-year-old male with an occupational history of dust exposure presenting to the ophthalmology clinic with bilateral painless upper eyelid swelling of one-week duration. The diagnosis of sarcoidosis was suspected based on clinical examination, laboratory analysis, and imaging showing mediastinal lymphadenopathy, further confirmed by pathologic examination showing noncaseating granulomas with the presence of some asteroid and Schaumann bodies. A treatment plan consisting of prednisone, folic acid, and azathioprine was effective for the patient, though azathioprine was eventually changed to methotrexate due to an allergic reaction. The patient is on a maintenance dose of methotrexate and is asymptomatic after a year of careful management and follow-up. This case emphasizes the significance of considering sarcoidosis as a differential diagnosis in patients presenting with bilateral dacryoadenitis.

Abnormal Presentation and Challenging Diagnosis of Mediastinal Lymphoma: A Case Report.

We describe a rare case of classical Hodgkin lymphoma (HL) in a 20-year-old female patient. She presented to our hospital with chest wall swelling after months of post-chest trauma management. The swelling was initially treated as an infected hematoma, and the patient was referred for surgical evacuation. During the surgery, the swelling was found to be a mass that extended to the mediastinum. A biopsy was taken, which later resulted in the diagnosis of a granular cell tumor (GCT). A decision on surgical resection by video-assisted thoracoscopic surgery (VATS) was taken after discussion with the multidisciplinary team of surgery, cardiothoracic surgery, oncology, pathology, and radiology. During the surgery, a frozen section biopsy was taken, which showed no features of lymphoma or granular cell tumors. The surgery was followed by a midline sternotomy to control the bleeding from an accidentally injured major vessel. The bleeding was controlled, and the mass was dissected and sent for histopathological examination. The histopathology showed nodular classical HL features, and the patient was referred for chemotherapy. In our case, the patient was initially diagnosed with GCT, but with complete resection and an adequate biopsy, the mass was found to be a classical HL. Possible cross-cellularity is questioned, and the possible correlation between the two findings encouraged us to report this case.

Metabolic Syndrome Associated with Tobacco and Caffeine Products Use Among Refugee Adolescents: Risk of Dyslipidemia.

INTRODUCTION: Due to their stressful lives, Palestinian refugees are prone to use cognitive enhancers (CE) and psychostimulant substances (PS). Recognising health problems associated with CE/PS use can indicate how preventive programs should be directed towards adolescents. Unfortunately, research has not thoroughly investigated the health problems related to tobacco and caffeine products, the most socially acceptable CE/PS among Palestinian refugee adolescents. METHODOLOGY: In 2021, schoolchildren from five Palestinian refugee camps (N=271) aged 12-<16 years agreed to give blood samples and to be interviewed to address the association between metabolic syndrome (MetS) and tobacco smoking, coffee, energy drinks (ED), black tea, and chocolate consumption. MetS was diagnosed based on International Diabetic Federation Criteria. To address the association, we used binary logistic regression models adjusted to age, gender, BMI, and central obesity. RESULTS: The prevalence of MetS was [17 (6.3%)]; (7.4%) in males, (5.1%) in females. The prevalence of substance use was as follows: ED [163 (48.9%)], coffee [255 (76.6%)], black tea [295 (89.1%)], cigarette [35 (10.5%)], waterpipe [59 (17.7%)], and chocolate [309 (93.6%)], with male predominance. Cigarette smokers have increased central obesity (p-value=0.024), and decreased HDL-cholesterol (p-value=0.015) than non-smokers. Similar results were observed for waterpipe smokers besides the increased levels of triglycerides (p-value=0.01). ED consumers have increased central obesity (p-value=0.03) and fast blood sugar (p-value=0.003) than non-consumers. Chocolate consumers have decreased central obesity (p-value=0.008) and increased HDL levels (p-value=0.04) than non-consumers. ED consumers were significantly at higher risk of MetS (OR=9.97, p-value=0.019) than non-consumers and chocolate consumers were at lower risk of MetS (OR=0.14, p-value=0.046) than non-consumers. Waterpipe smokers were at a higher risk of having increased plasma triglycerides than non-consumers (OR=3.4, p-value=0.03). CONCLUSION: The high prevalence of ED consumption and waterpipe smoking in Palestinian refugee adolescents is problematic. Their use was associated with higher odds of MetS, dyslipidemia, and central obesity, which justifies greater attention.