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Human immunodeficiency virus type 2 (HIV-2), the second retrovirus that causes the acquired immune deficiency syndrome (AIDS) in humans, is limited in its distribution to West Africa. We report cases in two Saudi families with HIV-2 infection and AIDS, resulting in death of the index cases-the husbands, while the wives and a daughter were maintained on antiretroviral therapy. When HIV viral loads were undetectable in initial assays, further testing confirmed the presence of HIV-2. In the first family, the 30-year-old wife was found to be HIV-positive after the diagnosis in her 30-year-old husband, who later died with AIDS. In the second family, HIV-2 infection was diagnosed in the 50-year-old wife and 18-year-old daughter of a man who had died of AIDS at the age of 48 years. Recognizing HIV-2 infection is essential for appropriate workup, assessment, therapy and care of the pregnant woman.

Objective: This study aimed to evaluate the intra- and inter-grader reliability of four evaluators using three different digital intraoral scanners and visual methods for typodontic Class II composite preparations., Materials and Methods: Ninety-five typodont teeth of Class II composite preparations were evaluated using traditional visual grading methods (VGM) and digital grading methods (DGM) using the same rubric. Three intraoral scanners were used to scan the Class II cavity preparation for the composite: i700 (Medit, Korea), Trios 4 (3Shape, Denmark), and Shinning 3D (Shinning 3D, China). The same rubric was used to score the visual and digital evaluations by calibrated examiners. Two-way ANOVA was used to compare method- and evaluator-based scores, accounting for the scanner type used., Results: The scores of the prepped typodont teeth were subjected to an interaction between the examiner and the evaluation technique. In addition, the mean total prepped teeth scores differed between examiners using VGM. A statistically significant interaction emerged between examiners and the evaluation technique employed to assess the total score of the prepped teeth:  F (9, 1504) = 3.893,  P  = 0.001, partial η2 = 0.023. The total prepped tooth score differed between the VGM and DGM groups. Lower ( P  < 0.05) intra-grader consistency was observed for the final scores when Class II preparations were evaluated using the VGM; however, this consistency improved when using the DGM., Conclusion: Examiners and evaluation methods affect student performance in Class II cavity preparations. The DGM may be more reliable and consistent within and between evaluators than the VGM is., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 THE AUTHORS.)

Human parechovirus, a member of the Picornaviridae family (PeVs), can lead to severe infections, including severe meningitis, meningoencephalitis, and sepsis-like syndrome. We report a case of human parechovirus-related encephalitis in a 52-year-old woman diagnosed with glioblastoma multiforme. She underwent surgical resection in June 2022. Unfortunately, her disease recurred, and she underwent a second resection in August 2022, followed by radiation therapy and Temozolomide therapy. She presented to the hospital with acute confusion followed by seizures, necessitating intubation for airway support. A cerebrospinal fluid (CSF) sample was obtained and processed using the Biofire FilmArray, which reported the detection of HSV-1. Despite being on Acyclovir, the patient did not show signs of improvement. Consequently, a second CSF sample was obtained and sent for next-generation sequencing (NGS), which returned a positive result for Parechovirus. In this presented case, the patient exhibited symptoms of an unknown infectious cause. The utilization of NGS and metagenomic analysis helped identify Parechovirus as the primary pathogen present, in addition to previously identified HSV. This comprehensive approach facilitated a thorough assessment of the underlying infection and guided targeted treatment. In conclusion, the application of NGS techniques and metagenomic analysis proved instrumental in identifying the root cause of the infection., (© 2024. The Author(s).)

Literature discussing endemic and regionally limited infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America is scarce. This Worldwide Network for Blood and Marrow Transplantation (WBMT) article is part one of two papers aiming to provide guidance to transplantation centres around the globe regarding infection prevention and treatment, and considerations for transplantation based on current evidence and expert opinion. These recommendations were initially formulated by a core writing team from the WBMT and subsequently underwent multiple revisions by infectious disease experts and HSCT experts. In this paper, we summarise the data and provide recommendations on several endemic and regionally limited viral and bacterial infections, many of which are listed by WHO as neglected tropical diseases, including Dengue, Zika, yellow fever, chikungunya, rabies, brucellosis, melioidosis, and leptospirosis., Competing Interests: Declaration of interests MBK declares honoraria from Gilead and an advisory board role at Gilead. RDLC declares honoraria from Gilead. NW declares honoraria and consultancy fees from Novartis; travel and honoraria from Kite Gilead; honoraria and research funding from Sanofi Genzyme; honoraria and speaker fees from Therakos Mallinckrodt; and travel fees from BMS Celgene. EB declares honoraria Novartis, Astellas, Alexion, Gilead, MSD, Keocyt, Jazz Pharmaceuticals, and Amgen; and travel fees from Jazz Pharmaceuticals, Novartis, and Amgen. JeS declares honoraria from Alexion, Sobi, and Takeda; consultancy fees from Alexion, Sobi, and Takeda; travel fees from Sobi; and an advisory board role at Prevail Therapeutics. JaS declares honoraria from MSD, Glead, TEVA, Atara, and Takeda. DW declares research funding from FATE therapeutics: Research Funding and Incyte. SKH declares honoraria from Pfizer, Novartis, Janssen, Therakos Mallinckrodt, Sanofi, and Roche. YA declares lecture fees from Novartis, AbbVie GK, and Astellas and consultancy honoraria from Meiji Seika, JCR Pharmaceuticals, and Kyowa Kirin. PL declares honoraria from Takeda, OctaPharma, and MSD. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

There is a scarcity of data on endemic and regionally limited fungal and parasitic infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America. This Worldwide Network for Blood and Marrow Transplantation (WBMT) Review is one of two papers aiming to provide guidance to transplantation centres worldwide regarding prevention, diagnosis, and treatment based on the currently available evidence and expert opinion. These recommendations were created and reviewed by physicians with expertise in HSCT or infectious disease, representing several infectious disease and HSCT groups and societies. In this paper, we review the literature on several endemic and regionally limited parasitic and fungal infections, some of which are listed as neglected tropical diseases by WHO, including visceral leishmaniasis, Chagas disease, strongyloidiasis, malaria, schistosomiasis, histoplasmosis, blastomycosis, and coccidioidomycosis., Competing Interests: Declaration of interests MBCK declares honoraria from Gilead and an advisory board role at Gilead. RDLC declares honoraria from Gilead. NW: declares honoraria from Novartis, Kite Gilead, Sanofi Genzyme, and Therakos Mallinckrodt; consultancy fees from Novartis; travel fees from Kite Gilead and BMS Celgene; research funding from Sanofi Genzyme; and speaker fees from Therakos Mallinckrodt. EB declares honoraria from Novartis, Astellas, Alexion, Jazz Pharmaceuticals, Gilead, MSD, Keocyt, and Amgen; and travel fees from Novartis, Jazz Pharmaceuticals, and Amgen. JeS declares consultancy fees from Alexion, Sobi, and Takeda; honoraria from Alexion, Sobi, and Takeda; travel fees from Sobi; and an advisory board role at Prevail Therapeutics. JaS declares honoraria from MSD, Glead, TEVA, Atara, and Takeda. DW declares research funding from FATE therapeutics and Incyte. SKH declares honoraria from Pfizer, Novartis, Janssen, Therakos Mallinckrodt, Sanofi, and Roche. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Mutations and aberrant gene expression during cellular differentiation lead to neurodevelopmental disorders, such as Prader-Willi syndrome (PWS), which results from the deletion of an imprinted locus on paternally inherited chromosome 15. We analyzed chromatin-associated RNA in human induced pluripotent cells (iPSCs) upon depletion of hybrid small nucleolar long non-coding RNAs (sno-lncRNAs) and 5' snoRNA capped and polyadenylated long non-coding RNAs (SPA-lncRNAs) transcribed from the locus deleted in PWS. We found that rapid ablation of these lncRNAs affects transcription of specific gene classes. Downregulated genes contribute to neurodevelopment and neuronal maintenance, while upregulated genes are predominantly involved in the negative regulation of cellular metabolism and apoptotic processes. Our data reveal the importance of SPA-lncRNAs and sno-lncRNAs in controlling gene expression in iPSCs and provide a platform for synthetic experimental approaches in PWS studies. We conclude that ncRNAs transcribed from the PWS locus are critical regulators of a transcriptional signature, which is important for neuronal differentiation and development., (© The Author(s) 2022. Published by Oxford University Press.)

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious with various possible routes of transmission, resulting in high mortality globally. Controversy exists regarding the vertical transmission of the SARS-CoV-2 infection to fetuses of COVID-19-infected women. The aim of this study was to investigate the possibility of the vertical transmission of SARS-CoV-2 from COVID-19-infected mothers to their neonates., Materials and Methods: We prospectively collected demographical and clinical characteristics of 31 COVID-19 positive pregnant women and their neonates. All mothers and neonates were tested for SARS-CoV-2 infection using the real-time polymerase chain reaction on nasopharyngeal swabs and breast milk samples. Antenatal and placental abnormalities were ultrasonically and histopathologically examined. In cord blood samples, the immunoglobins (Ig) M and IgG were estimated qualitatively., Results: The women's mean age and gestational age were 31 years and 38 weeks, respectively, with 58% undergoing an elective cesarean section. Gestational diabetes was reported in 29% of cases, 64.5% of women were medically free and only 16.12% were symptomatic. A normal antenatal ultrasound was observed in 77.42% of cases. Nine cord blood samples were positive for IgG. Villous infarction (24%), villous agglutination, and chorangiosis (51%), accelerated villous maturation (21%) and reduced and hypercoiling were reported for 6.97% of the umbilical cords. Three newborns had possible vertical transmission of SARS-CoV-2 infection, of which, two were preterm and IUFD. The third neonate was born full-term, admitted to NICU and later discharged in good health., Conclusion: Our findings support the possibility of the direct vertical transmission of the SARS-CoV-2 infection to neonates from infected mothers. Further studies with a larger sample size are required to validate the current findings.

Thyroid cancer is the most prevalent endocrine cancer among the female population in the Kingdom of Saudi Arabia (KSA) and the ninth most common in the male population in Saudi Arabia. Over the past years, an increasing incidence of thyroid cancer has been reported in Saudi Arabia. However, the etiology of thyroid cancer is still not clear. Therefore, this study aimed to estimate thyroid cancer incidence and mortality trends in Saudi Arabia from 1990 to 2019. The current study utilized the Global Burden of Disease and the Institute for Health Metrics and Evaluation databases to extract prevalence data of thyroid cancer in Saudi Arabia from 1990 to 2019. Moreover, the current project utilizes Global Burden of Disease (GBD) web-based tools to visualize these data. In total, 23,846 cases (17,220 females and 6626 males) were diagnosed with thyroid cancer in Saudi Arabia from 1990 to 2019. The incidence is higher in females than in males. Over these 30 years, women's incidence steadily increased by 15-fold versus a 22-fold increase in men. Moreover, there were 2056 deaths in total caused by thyroid cancer in KSA. The mortality rate in women steadily increased by threefold in the same period. However, the increase in mortality was higher in males (sixfold). A high percentage of YLLs was observed in males, with around 24.8% ranging from 30 to 34 and 40 to 45 years. Thyroid cancer incidence rates have increased exponentially between 1990 and 2019. The expansion of the incidence of thyroid cancer in Saudi Arabia could be due to the increased development in detection and diagnosis. The current study provided evidence of the need to increase awareness and diagnosis in the male population.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its resulting disease, coronavirus disease 2019 (COVID-19), has spread to millions of people worldwide. Preliminary data from organ transplant recipients have shown reduced seroconversion rates after the administration of different SARS-CoV-2 vaccination platforms. However, it is unknown whether different vaccination platforms provide different levels of protection against SARS-CoV-2. To answer this question, we prospectively studied 431 kidney and liver transplant recipients (kidney: n = 230; liver: n = 201) who received either the ChAdOx1 vaccine (n = 148) or the BNT-162b2 vaccine (n = 283) and underwent an assessment of immunoglobulin M/immunoglobulin G spike antibody levels. The primary objective of the study is to directly compare the efficacy of two different vaccine platforms in solid organ transplant recipients by measuring of immunoglobulin G (IgG) antibodies against the RBD of the spike protein (anti-RBD) two weeks after first and second doses. Our secondary endpoints were solicited specific local or systemic adverse events within 7 days after the receipt of each dose of the vaccine. There was no difference in the primary outcome between the two vaccine platforms in patients who received two vaccine doses. Unresponsiveness was mainly linked to diabetes. The rate of response after the first dose among younger older patients was significantly larger; however, after the second dose this difference did not persist (p = 0.079). Side effects were similar to those that were observed during the pivotal trials., (© 2022. The Author(s).)

Acute myeloid leukaemia (AML) cells interact and modulate components of their surrounding microenvironment into their own benefit. Stromal cells have been shown to support AML survival and progression through various mechanisms. Nonetheless, whether AML cells could establish beneficial metabolic interactions with stromal cells is underexplored. By using a combination of human AML cell lines and AML patient samples together with mouse stromal cells and a MLL-AF9 mouse model, here we identify a novel metabolic crosstalk between AML and stromal cells where AML cells prompt stromal cells to secrete acetate for their own consumption to feed the tricarboxylic acid cycle (TCA) and lipid biosynthesis. By performing transcriptome analysis and tracer-based metabolic NMR analysis, we observe that stromal cells present a higher rate of glycolysis when co-cultured with AML cells. We also find that acetate in stromal cells is derived from pyruvate via chemical conversion under the influence of reactive oxygen species (ROS) following ROS transfer from AML to stromal cells via gap junctions. Overall, we present a unique metabolic communication between AML and stromal cells and propose two different molecular targets, ACSS2 and gap junctions, that could potentially be exploited for adjuvant therapy., Competing Interests: NV, VC, RA, GP, AR, MJ, EG, YA, AC, AE, FS, MR, SP, JC, JS, MR, LA, UG, PG No competing interests declared, (© 2022, Vilaplana-Lopera et al.)

Numerous studies have been published regarding outcomes of cancer patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causing the coronavirus disease 2019 (COVID-19) infection. However, most of these are single-center studies with a limited number of patients. To better assess the outcomes of this new infection in this subgroup of susceptible patients, we performed a systematic review and meta-analysis to evaluate the impact of COVID-19 infection on cancer patients. We performed a literature search using PubMed, Web of Science, and Scopus for studies that reported the risk of infection and complications of COVID-19 in cancer patients and retrieved 22 studies (1018 cancer patients). The analysis showed that the frequency of cancer among patients with confirmed COVID-19 was 2.1% (95% confidence interval [CI]: 1.3-3) in the overall cohort. These patients had a mortality of 21.1% (95% CI: 14.7-27.6), severe/critical disease rate of 45.4% (95% CI: 37.4-53.3), intensive care unit (ICU) admission rate of 14.5% (95% CI: 8.5-20.4), and mechanical ventilation rate of 11.7% (95% CI: 5.5-18). The double-arm analysis showed that cancer patients had a higher risk of mortality (odds ratio [OR]=3.23, 95% CI: 1.71-6.13), severe/critical disease (OR=3.91, 95% CI: 2.70-5.67), ICU admission (OR=3.10, 95% CI: 1.85-5.17), and mechanical ventilation (OR=4.86, 95% CI: 1.27-18.65) than non-cancer patients. Furthermore, cancer patients had significantly lower platelet levels and higher D-dimer levels, C-reactive protein levels, and prothrombin time. In conclusion, these results indicate that cancer patients are at a higher risk of COVID-19 infection-related complications. Therefore, cancer patients need diligent preventive care measures and aggressive surveillance for earlier detection of COVID-19 infection.

Background: Data on SARS-CoV-2 in infants ≤ 90 days are limited with conflicting reports regarding its presentation and outcomes., Methods: We conducted an ambispective cohort study using prospectively collected Health Electronic Surveillance Network Database by the Ministry of Health, Saudi Arabia. Infants of ≤ 90 days of age who had a positive RT-PCR test for SARS-CoV-2 virus were included. Patients were divided in Early neonatal (0-6 days), late neonatal (7-27 days), and post- neonatal (28-90 days) groups and were compared for clinical characteristics and outcomes by contacting parents and collecting information retrospectively., Results: Of 1,793 infants, 898 infants were included for analysis. Most infants in the early neonatal group had no features of infection (tested based on maternal positivity), whereas most infants in the late and post- neonatal groups were tested because of clinical features of infection. Fever and respiratory signs were the most common presenting feature in the late and post-neonatal groups. Hospitalization was higher in the early neonatal group (80%), compared to the two other groups. The overall mortality in the cohort was 1.6%., Conclusion: SARS-CoV-2 infection in infants ≤ 90 days might not be as rare as previously reported. The clinical presentation varies based on age at positive RT-PCR result., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shaiba, Hadid, Altirkawi, Alnamnakani, Almutayliq, Alharbi, Hijazi, AlMoosa, AlSaud, Murshid, AlMuhanna, Aldawsari, Bin Hadyan, Almaghrabi, Alsofayan, Alahmari, Almuzaini, Alamri, Khan and Shah.)

Introduction: Multisystem inflammatory syndrome in neonates (MIS-N) related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has increasingly been reported worldwide amid the spread of the SARS-CoV-2 pandemic., Methods: We searched PubMed, EMBASE, and CINAHL and preprint servers (BioRxiv.org and MedRxiv.org) using a specified strategy integrating Medical Subject Headings terms and keywords until October 20, 2021. Our aim was to systematically review demographic profiles, clinical features, laboratory parameters, complications, treatments, and outcomes of neonates with MIS-N. Studies were selected when fulfilling the inclusion criteria. Articles were included if they fulfilled the World Health Organization (WHO), Centers for Disease Control (CDC) definitions of MIS-C, or our proposed definition., Results: Sixteen reports of MIS-N including 47 neonates meeting MIS-N criteria were identified. Presentation included cardiovascular compromise (77%), respiratory involvement (55%), and fever in (36%). Eighty-three percent of patients received steroids, and 76% received immunoglobulin. Respiratory support was provided to 60% of patients and inotropes to 45% of patients. Five (11%) neonates died., Conclusion: The common presentation of MIS-N included cardiorespiratory compromise with the possibility of high mortality. Neonates with MIS-N related to SARS-CoV-2 may be at higher risk of adverse outcomes., (© 2022 S. Karger AG, Basel.)

Background: Medical training programs candidate's interview is an integral part of the residency matching process. During the coronavirus disease 2019 (COVID-19) pandemic, conducting these interviews was challenging due to infection prevention restrains (social distancing, namely) and travel restrictions. E-interviews were implemented by the Saudi Commission for Healthcare Specialties (SCFHS) since the matching cycle of March 2020 to hold the interviews in a safer virtual environment while maintaining the same matching quality and standards., Aim: This study was conducted to assess the medical training residency program applicants' satisfaction, stress, and other perspectives for the (SCFHS) March 2020 Matching-cycle conducted through an urgently implemented E-interviews process., Method: A cross-sectional, nationwide survey (Additional file 1) was sent to 4153 residency-nominated applicants to the (SCFHS) March 2020 cycle., Results: Among the 510 candidates who responded, 62.2% applied for medical specialties, 20.2% applied for surgical specialties, and 17.6% applied for critical care and emergency specialties. Most respondents (61.2%) never had previous experience with web-based video conferences. Most respondents (80.2%) used the Zoom application to conduct the current E-interviews, whereas only 15.9% used the FaceTime application. 63.3% of the respondents preferred E-interviews over in-person interviews, and 60.6% rated their experience as very good or excellent. 75.7% of the respondents agreed that all their residency program queries were adequately addressed during the E-interviews. At the same time, 52.2% of them agreed that E-interviews allowed them to represent themselves accurately. 28.2% felt no stress at all with their E-interviews experience, while 41.2% felt little stressed and only 8.2% felt highly stressed. The factors that were independently and inversely associated with applicants' level of stress with E-interviews experience were their ability to represent themselves during the interviews (p = 0.001), cost-savings (p < 0.001), their overall rating of the E-interviews quality (p = 0.007) and the speed of the internet connection (p < 0.006)., Conclusion: Videoconferencing was implemented on an urgent basis during the COVID-19 pandemic in the medical residency application process in Saudi Arabia. It was perceived as an adequate and promising tool to replace in-person interviews in the future. Applicants' satisfaction was mainly driven by good organization, cost-saving, and their ability to present themselves. Future studies to enhance this experience are warranted., (© 2021. The Author(s).)

Context: Exploring clinical characteristics of coronavirus disease-19 (COVID-19) in children may help in prevention and treatment guidelines., Aims: The aim of the to describe the spectrum of pediatric COVID-19 in Saudi Arabia., Settings and Design: A multicenter, retrospective, cross-sectional study involving pediatric COVID-19 patients across all Saudi regions., Methods: All patients aged between 2 months and 18 years with a confirmed diagnosis of COVID-19 were included. The primary end point was the hospitalization., Statistical Analysis Used: Descriptive statistics were used to describe the baseline demographic data and clinical characteristics. Numerical data were explored using Kolmogorov-Smirnov test and Shapiro-Wilk test, while Chi-square or Fisher's exact test were used for categorical data., Results: Among the 654 pediatric COVID-19 patients, 4.7% ( n = 31) were hospitalized, with one patient only needing pediatric intensive care admission. Sex, breastfeeding, birth status, and the patients' living environment showed no significant association with hospitalization. Most children (80.3%, n = 525) were symptomatic, with two symptoms that were significantly associated with admission, namely, vomiting ( P = 0.007) and nausea ( P = 0.026). History of admission within the last year was identified in 10.4% ( n = 68) children but had no association with worse outcome. The median duration of hospitalization for the entire group was 5.5 days, with longest hospital stay for age group 7-12 years (median 6 days)., Conclusions: COVID-19 is usually a milder disease in children. Although having preexisting medical conditions was linked to a longer hospitalization, it was not associated with worse outcome. Continuous surveillance will allow additional characterization of the burden and outcomes of pediatric COVID-19-associated hospitalizations., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Annals of Thoracic Medicine.)

Urinary tract infection (UTI) is the most common bacterial disease in childhood worldwide and may have significant adverse consequences, particularly for young children. In this guideline, we provide the most up-to-date information for the diagnosis and management of community-acquired UTI in infants and children aged over 90 days up to 14 years. The current recommendations given by the American Academy of Pediatrics Practice guidelines, Canadian Pediatric Society guideline, and other international guidelines are considered as well as regional variations in susceptibility patterns and resources. This guideline covers the diagnosis, therapeutic options, and prophylaxis for the management of community-acquired UTI in children guided by our local antimicrobial resistance pattern of the most frequent urinary pathogens. Neonates, infants younger than three months, immunocompromised patients, children recurrent UTIs, or renal abnormalities should be managed individually because these patients may require more extensive investigation and more aggressive therapy and follow up, so it is considered out of the scope of these guidelines. Establishment of children-specific guidelines for the diagnosis and management of community-acquired UTI can reduce morbidity and mortality. We present a clinical statement from the Saudi Pediatric Infectious Diseases Society (SPIDS), which concerns the diagnosis and management of community-acquired UTI in children., (© 2021 Publishing services provided by Elsevier B.V. on behalf of King Faisal Specialist Hospital & Research Centre (General Organization), Saudi Arabia.)

Background: Vertical transmission of SARS-CoV-2 is under investigation. A few reports suggest the possibility of SARS-CoV-2 transmission from mothers to their neonates. Most neonates have mild symptoms, but some develop multisystem involvement and shock. Case Presentation: We report two cases of possible SARS-CoV-2 vertical transmission from mothers to their neonates. The first case shows maternal infection with SARS-CoV-2 in the second trimester followed by recurrent infection in the third trimester right before the delivery. The infant demonstrated respiratory distress soon after delivery along with myocardial dysfunction and multi-organ system involvement. The second case shows maternal infection with SARS-COV-2 at the time of delivery with preterm labor secondary to placental abruption, with that delivery resulting in the preterm neonate requiring non-invasive ventilation with multisystem involvement in the context of persistently positive SARS-COV-2 PCR in the neonate. Both neonates were treated with IVIG along with steroids. Both neonates recovered fully and were discharged and allowed to go home. Conclusion: In neonates, COVID-19 usually presents as an asymptomatic or mild illness; some may develop a more severe course. Our two cases, however, demonstrate that multisystem involvement, although rare, is possible. This report also supports the current evidence of possible vertical transmission from mothers to their neonates. This multisystem involvement might be underreported and should be considered in neonates with respiratory distress when born to mothers suffering of COVID-19. Clinical Trial Registration: [KSUMC], identifier [No#98763298]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shaiba, Hadid, Altirkawi, Bakheet, Alherz, Hussain, Sobaih, Alnemri, Almaghrabi, Ahmed, Arafah, Jarallah, Bukhari and Alzamil.)

Replication stress, a major cause of genome instability in cycling cells, is mainly prevented by the ATR-dependent replication stress response pathway in somatic cells. However, the replication stress response pathway in embryonic stem cells (ESCs) may be different due to alterations in cell cycle phase length. The transcription factor MYBL2, which is implicated in cell cycle regulation, is expressed a hundred to a thousand-fold more in ESCs compared with somatic cells. Here we show that MYBL2 activates ATM and suppresses replication stress in ESCs. Consequently, loss of MYBL2 or inhibition of ATM or Mre11 in ESCs results in replication fork slowing, increased fork stalling and elevated origin firing. Additionally, we demonstrate that inhibition of CDC7 activity rescues replication stress induced by MYBL2 loss and ATM inhibition, suggesting that uncontrolled new origin firing may underlie the replication stress phenotype resulting from loss/inhibition of MYBL2 and ATM. Overall, our study proposes that in addition to ATR, a MYBL2-MRN-ATM replication stress response pathway functions in ESCs to control DNA replication initiation and prevent genome instability., (©2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Objectives: Lung transplant guidelines recommend nebulized amphotericin B with or without systemic antifungal agents for fungal prophylaxis. However, amphotericin formulation, dosing, and frequency vary between studies. We assessed the safety and effectiveness of nebulized amphotericin B to prevent Aspergillus infection in 2 regimens, ie, twice daily compared with 3 times daily., Materials and Methods: This was a single-center retrospective cohort study. We included patients at least 14 years old who underwent lung transplant and received nebulized amphotericin B alone or in combination with another antifungal agent either twice daily or 3 times daily. The primary endpoint was the incidence of lung Aspergillus infection, and the secondary endpoints were nebulized amphotericin B side effects and breakthrough Aspergillus infection., Results: A total of 84 patients were included. The group given nebulized amphotericin twice daily had a higher rate of Aspergillus infection at 17% compared with 4% in the group treated 3 times daily (P = .24). No serious side effects were reported, but coughing and diarrhea were more common in patients who received amphotericin B 3 times daily., Conclusions: A systemic antifungal agent combined with nebulized amphotericin either twice or 3 times daily has been effective to prevent Aspergillus infection. Nebulized amphotericin twice daily may be a more viable option to increase a patient's adherence and decrease medication cost and side effects. However, a larger randomized controlled trial is needed to determine the best dosing regimen for nebulized amphotericin B as a fungal prophylaxis after lung transplant.

The World Health Organization (WHO), on March 11 th 2020, upgraded the status of the novel coronavirus disease (COVID-19) from epidemic to pandemic. Over two million individuals have been infected with SARS-CoV-2, the virus causing COVID-19, and as of April, 14 th 2020, there were over 5000 confirmed cases in Saudi Arabia (SA). Many countries, including SA, have imposed major restrictions on travel, and everyday life, and the implications of these necessary changes are being felt in liver transplant (LT) centers in SA. Concerns remain that there is an increased risk for individuals over 65 years of age, with underlying medical conditions, or for those who are immunocompromised. Therefore, the Saudi Association for the Study of Liver Diseases and Transplantation (SASLT) established an urgent task force to launch a statement that can be utilized by LT centers as a guidance in the management of patients with advanced liver disease from the time of LT listing to the post-operative care of transplanted patients., Competing Interests: None

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by blood cytopenias that occur as a result of somatic mutations in hematopoietic stem cells (HSC). MDS leads to ineffective hematopoiesis, and as many as 30% of patients progress to acute myeloid leukemia (AML). The mechanisms by which mutations accumulate in HSC during aging remain poorly understood. Here we identify a novel role for MYBL2 in DNA double-strand break (DSB) repair in HSC. In patients with MDS, low MYBL2 levels associated with and preceded transcriptional deregulation of DNA repair genes. Stem/progenitor cells from these patients display dysfunctional DSB repair kinetics after exposure to ionizing radiation (IR). Haploinsufficiency of Mybl2 in mice also led to a defect in the repair of DSBs induced by IR in HSC and was characterized by unsustained phosphorylation of the ATM substrate KAP1 and telomere fragility. Our study identifies MYBL2 as a crucial regulator of DSB repair and identifies MYBL2 expression levels as a potential biomarker to predict cellular response to genotoxic treatments in MDS and to identify patients with defects in DNA repair. Such patients with worse prognosis may require a different therapeutic regimen to prevent progression to AML. Significance: These findings suggest MYBL2 levels may be used as a biological biomarker to determine the DNA repair capacity of hematopoietic stem cells from patients with MDS and as a clinical biomarker to inform decisions regarding patient selection for treatments that target DNA repair. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/20/5767/F1.large.jpg Cancer Res; 78(20); 5767-79. ©2018 AACR ., (©2018 American Association for Cancer Research.)

During somatic reprogramming, Yamanaka's pioneer factors regulate a complex sequence of molecular events leading to the activation of a network of pluripotency factors, ultimately resulting in the acquisition and maintenance of a pluripotent state. Here, we show that, contrary to the pluripotency factors studied so far, overexpression of Mybl2 inhibits somatic reprogramming. Our results demonstrate that Mybl2 levels are crucial to the dynamics of the reprogramming process. Mybl2 overexpression changes chromatin conformation, affecting the accessibility of pioneer factors to the chromatin and promoting accessibility for early immediate response genes known to be reprogramming blockers. These changes in the chromatin landscape ultimately lead to a deregulation of key genes that are important for the mesenchymal-to-epithelial transition. This work defines Mybl2 level as a gatekeeper for the initiation of reprogramming, providing further insights into the tight regulation and required coordination of molecular events that are necessary for changes in cell fate identity during the reprogramming process., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The aminoglycoside-modifying enzyme AAC(6')-Ib is common among carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strains. We investigated amikacin (AMK) activity against 20 AAC(6')-Ib-producing CR-Kp strains. MICs clustered at 16 to 32 μg/ml. By the time-kill study, AMK (1× and 4× the MIC) was bactericidal against 30% and 85% of the strains, respectively. At achievable human serum concentrations, however, the majority of strains showed regrowth, suggesting that AAC(6')-Ib confers intermediate AMK resistance. AMK and trimethoprim-sulfamethoxazole (TMP-SMX) were synergistic against 90% of the strains, indicating that the combination may overcome resistance., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

We measured in vitro activity of plazomicin, a next-generation aminoglycoside, and other aminoglycosides against 50 carbapenem-resistant Klebsiella pneumoniae strains from two centers and correlated the results with the presence of various aminoglycoside-modifying enzymes (AMEs). Ninety-four percent of strains were sequence type 258 (ST258) clones, which exhibited 5 ompK36 genotypes; 80% and 10% of strains produced Klebsiella pneumoniae carbapenemase 2 (KPC-2) and KPC-3, respectively. Ninety-eight percent of strains possessed AMEs, including AAC(6')-Ib (98%), APH(3')-Ia (56%), AAC(3)-IV (38%), and ANT(2")-Ia (2%). Gentamicin, tobramycin, and amikacin nonsusceptibility rates were 40, 98, and 16%, respectively. Plazomicin MICs ranged from 0.25 to 1 μg/ml. Tobramycin and plazomicin MICs correlated with gentamicin MICs (r = 0.75 and 0.57, respectively). Plazomicin exerted bactericidal activity against 17% (1× MIC) and 94% (4× MIC) of strains. All strains with AAC(6')-Ib were tobramycin-resistant; 16% were nonsusceptible to amikacin. AAC(6')-Ib combined with another AME was associated with higher gentamicin, tobramycin, and plazomicin MICs than AAC(6')-Ib alone (P = 0.01, 0.0008, and 0.046, respectively). The presence of AAC(3)-IV in a strain was also associated with higher gentamicin, tobramycin, and plazomicin MICs (P = 0.0006, P < 0.0001, and P = 0.01, respectively). The combination of AAC(6')-Ib and another AME, the presence of AAC(3)-IV, and the presence of APH(3')-Ia were each associated with gentamicin resistance (P = 0.0002, 0.003, and 0.01, respectively). In conclusion, carbapenem-resistant K. pneumoniae strains (including ST258 clones) exhibit highly diverse antimicrobial resistance genotypes and phenotypes. Plazomicin may offer a treatment option against strains resistant to other aminoglycosides. The development of molecular assays that predict antimicrobial responses among carbapenem-resistant K. pneumoniae strains should be a research priority., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)