Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Genetic Studies on 167 Pediatric ALL Patients from Different Areas of Pakistan Confirm a Low Frequency of the Favorable Prognosis Fusion Oncogene TEL-AML1

TEL-AML1 fusion oncogene (t 12; 21) is the most common chromosomal abnormality in childhood acute lymphoblastic leukemia (ALL). This translocation is associated with a good prognosis and rarely shows chemotherapeutic resistance to 3-drug based remission induction phase of treatment as well as overall treatment. Thus, the higher the frequency of this fusion oncogene, the easier to manage childhood ALL in a given region with less intensive chemotherapy. Although global frequency of TEL-AML1 has been reported to be 20-30%, a very low frequency has been found in some geographical regions, including one study from Lahore, Punjab, Pakistan and others from India. The objective of present study was to investigate if this low frequency of TELAML1 in pediatric ALL is only in Lahore region or similar situation exists at other representative oncology centers of Pakistan. A total of 167 pediatric ALL patients were recruited from major pediatric oncology centers situated in Lahore, Faisalabad, Peshawar and Islamabad. Patients were tested for TEL-AML1 using nested reverse transcription polymerase chain reaction (RT-PCR). Only 17 out of 167 (10.2%) patients were found to be TEL-AML1 positive. TEL-AML1+ ALL patients had favorable prognosis, most of them (82.4%, 14/17) showing early remission and good overall survival. Thus, our findings indicate an overall low frequency of TEL-AML1 in Pakistan pediatric ALL patients, in accordance with lower representation of this prognostically important genetic abnormality in other less developed countries, specifically in south Asia, thus associating it with poor living standards in these ethnic groups. It also indicates ethnic and geographical differences in the distribution of this prognostically important genetic abnormality among childhood ALL patients, which may have a significant bearing on ALL management strategies in different parts of the world.
Developmental Nicotine Exposure Alters Synaptic Input to Hypoglossal Motoneurons and Is Associated with Altered Function of Upper Airway Muscles

Abstract Nicotine exposure during the fetal and neonatal periods [developmental nicotine exposure (DNE)] is associated with ineffective upper airway protective reflexes in infants. This could be explained by desensitized chemoreceptors and/or mechanoreceptors, diminished neuromuscular transmission or altered synaptic transmission among central neurons, as each of these systems depend in part on cholinergic signaling through nicotinic AChRs (nAChRs). Here, we showed that DNE blunts the response of the genioglossus (GG) muscle to nasal airway occlusion in lightly anesthetized rat pups. The GG muscle helps keep the upper airway open and is innervated by hypoglossal motoneurons (XIIMNs). Experiments using the phrenic nerve-diaphragm preparation showed that DNE does not alter transmission across the neuromuscular junction. Accordingly, we used whole cell recordings from XIIMNs in brainstem slices to examine the influence of DNE on glutamatergic synaptic transmission under baseline conditions and in response to an acute nicotine challenge. DNE did not alter excitatory transmission under baseline conditions. Analysis of cumulative probability distributions revealed that acute nicotine challenge of P1–P2 preparations resulted in an increase in the frequency of nicotine-induced glutamatergic inputs to XIIMNs in both control and DNE. By contrast, P3–P5 DNE pups showed a decrease, rather than an increase in frequency. We suggest that this, together with previous studies showing that DNE is associated with a compensatory increase in inhibitory synaptic input to XIIMNs, leads to an excitatory-inhibitory imbalance. This imbalance may contribute to the blunting of airway protective reflexes observed in nicotine exposed animals and human infants.
CCL21 and prognosis in acute coronary syndrome

syndromes (ACS) has improved markedly in the last decades through the development of new biomarkers such as the troponins, natriuretic peptides and risk stratification scoring systems. However, there has been a shift in the epidemiological characteristics of myocardial infarction (MI) with an increasing number of patients presenting with non-ST-segment elevation MI (NSTEMI) where the ability to predict shortand longterm outcomes is more limited [1, 2] . Exploration of novel biomarkers reflecting activated pathways not accounted for by current risk markers could improve diagnosis and prognostic classification of patients with ACS and identify new targets for therapy. Chemokines are small heparin-binding proteins that together with their chemokine receptors are critical mediators of cell migration during immune surveillance and homeostasis. The homeostatic chemokines, CCL19 and CCL21 and their common receptor CCR7, play a pivotal role in T cell and dendritic-cell trafficking into lymphoid tissue, and their function was originally thought to be restricted to immune cell homeostasis. However, findings during the last decade suggest that these chemokines may have pleiotropic effects and are involved in inflammatory responses in non-lymphoid tissue such as atherosclerotic lesions implying a complex Editorial
HYDATID CYST - DIFFERENT ORGAN INVOLVEMENT: A PROSPECTIVE AND RETROSPECTIVE STUDY

Hydatid disease/ hydatidosis is an endemic disease in sheep rearing countries. It has a world wide distribution and poses an important public health problem that is influenced by people’s socioeconomic status and migration which spreads this disease. It is caused by the larval form of Echinococcus granulosus. The main host being the dog, the intermediate hosts are sheep, cattle, pigs and horses. Hydatid disease manifests when man becomes an accidental intermediate host. All sites of the body can be possible locations of the parasite. The most common sites are the liver followed by lung, kidney, bone and brain with the rare sites being breast, adrenals, heart, intra arterial, broad ligament and others. We conducted a retrospective and prospective study of different organ involvement of hydatid cyst reported in our department. The study spanned over a period of sixteen years and seven months, from March 1993 - October 2009. 34 specimens were received in the department of Pathology, SVIMS, Tirupati, which were reported as cases of hydatid cyst involving different organs, which included rare sites such as brain, kidney, breast, synovial tissue and retrouterine.
Variant frequencies of KCNQ1, KCNH2, and SCN5A in a Chinese inherited arrhythmia cohort and other disease cohorts undergoing genetic testing

KCNQ1, KCNH2, and SCN5A are the most common genes responsible for long QT syndrome and Brugada syndrome. However, the genetic variant frequencies of the three genes in different Chinese disease cohorts are largely unknown. In this study, we analyzed the genetic variants of KCNQ1, KCNH2, and SCN5A in patients from seven cohorts (total N = 11945, including patients clinically suspected to have inherited arrhythmia [n = 122], other cardiovascular diseases [n = 1045], epilepsy [n = 4797], or other diseases [n = 5841], and healthy controls [n = 140]) who had undergone genetic testing. All of these variants were identified via genetic testing by two Chinese companies using the Hi‐Seq 2000 platform. A total of 1018 variants (minor allele frequency <0.01) were identified, with 186 (18%), 374 (37%), and 458 (46%) variants in the coding exons of KCNQ1, KCNH2, and SCN5A, respectively. Of these variants, 84% had unknown or uncertain clinical significance. The frequency of identified ClinVar pathological/likely pathological variants was higher for KCNQ1 (13/186, 7.0%) than for KCNH2 (6/374, 1.6%) or SCN5A (10/458, 2.2%), and KCNH2 held the highest number and proportion of radical mutations (30/374, 8%). The prevalence of variants was highest in the inherited arrhythmia cohort (35%) and lowest in the healthy controls (<4%), as expected. Noticeably, the variant prevalence was relatively high in the epilepsy cohort (27%). Finally, only 22 of the 82 variants (26%) identified by both companies had consistent interpretations of pathogenicity between the two companies. Our study demonstrated a comprehensive spectrum of variants in KCNQ1, KCNH2, and SCN5A in a large number of Chinese individuals, including inherited arrhythmia, cardiovascular diseases, and epilepsy. The detailed variant frequency data of each cohort could serve as a valuable reference to facilitate further variant classification by others. We also found that the interpretations of pathogenicity differed greatly among the companies.
The quality and safety of locum doctors: a narrative review

Summary Locum doctors are often perceived to present greater risks of causing harm to patients than permanent doctors. After eligibility and quality assessment, eight empirical and 34 non-empirical papers were included in a narrative synthesis to establish what was known about the quality and safety of locum medical practice. Empirical literature was limited and weak methodologically. Locums enabled healthcare organisations to maintain appropriate staffing levels and allowed staffing flexibility, but they also gave rise to concerns about continuity of care, patient safety, team function and cost. There was some evidence to suggest that the way locum doctors are recruited, employed and used by organisations, may result in a higher risk of harm to patients. A better understanding of the quality and safety of locum working is needed to improve the use of locum doctors and the quality and safety of patient care that they provide.
Cluster Analysis of Residential Personal Exposure to ELF Magnetic Field in Children: Effect of Environmental Variables

Personal exposure to Extremely Low Frequency Magnetic Fields (ELF MF) in children is a very timely topic. We applied cluster analysis to 24 h indoor personal exposures of 884 children in France to identify possible common patterns of exposures. We investigated how electric networks near child home and other variables potentially affecting residential exposure, such as indoor sources of ELF MF, the age and type of the residence and family size, characterized the magnetic field exposure patterns. We identified three indoor personal exposure patterns: children living near overhead lines of high (63–150 kV), extra-high (225 kV) and ultra-high voltage (400 kV) were characterized by the highest exposures; children living near underground networks of low (400 V) and mid voltage (20 kV) and substations (20 kV/400 V) were characterized by mid exposures; children living far from electric networks had the lowest level of exposure. The harmonic component was not relevant in discriminating the exposure patterns, unlike the 50 Hz or broadband (40–800 Hz) component. Children using electric heating appliances, or living in big buildings or in larger families had generally a higher level of personal indoor exposure. Instead, the age of the residence was not relevant in differentiating the exposure patterns.
Disease Predilection and Molecular Heterogeneity of the Murine Aorta are Intrinsic to the Vessel Wall

Vascular diseases such as atherosclerosis or aneurysmal disease preferentially affect different parts of the arterial system. Despite this heterogeneous pattern of disease within the arterial system, the contribution of different smooth muscle cell phenotypes to this pattern has not been well studied. We investigated aortic disease susceptibility and epigenetic differences within different regions of the murine aorta. Quantitative analyses showed more numerous atherosclerotic plaques and larger aneurysms in the ascending aorta compared to the descending thoracic aorta in apoE and fbn1 mice, respectively. Interferon-γ and transforming growth factor-β responses, characteristic of these disease processes, were greater in the ascending vs. descending thoracic aorta. There was differential gene expression within the aorta and a “Hox code” was found for the murine arterial vasculature along the anterior–posterior axis. Transplantation of ascending and descending thoracic aortic segments to the abdominal aorta of syngeneic recipients confirmed that the propensity for atherosclerotic disease and the expression of selective molecular markers were innate properties of the vessel wall and not dependent on regional hemodynamic factors or paracrine signals from surrounding tissues. The epigenetic changes were also stable in cultured cells despite identical in vitro conditions. Our work supports the concept of intrinsic differences between vascular smooth muscle cells from various arteries that may play a role in disease pathogenesis. ACKNOWLEDGEMENTS I thank my tremendous mentor George Tellides for an outstanding and productive opportunity to learn through this project. Special thanks goes to Lingfeng Qin for his invaluable contributions to this work. I also appreciate the assistance from members of the Vascular Biology and Therapeutics Program and the Department of Surgery. This work was supported by the National Institutes of Health (PO1 HL70295). Sheng-fu Larry Lo received a Research Training Fellowship for Medical Students from the Howard Hughes Medical Institute. To my loving family and friends, I am ever grateful for your wonderful support along the way. Finally, to my beautiful fiancee, Alice, I love you very much and could not have made it without you!
Overexpression of pink1 or parkin in indirect flight muscles promotes mitochondrial proteostasis and extends lifespan in Drosophila melanogaster

Dysfunctional mitochondria have been implicated in aging and age-related disorders such as Parkinson’s diseases (PD). We previously showed that pink1 and parkin, two familial PD genes, function in a linear pathway to maintain mitochondrial integrity and function. Studies of mammalian cell lines also suggest that these genes regulate mitochondrial autophagy(mitophagy). Overexpressing Parkin promotes proteostasis and function of aged muscles both in fruit flies and mice, and recent studies also indicated that mitochondrial ubiquitination are accumulated in aged muscles. However, the underlying mechanisms for pink1 and parkin mediated mitophagy on longevity is not fully understood. Here, we found that mitochondrial ubiquitination increased in indirect flight muscles (IFMs) in an age-dependent manner. Overexpression of pink1 or parkin in IFMs can abolish mitochondrial ubiquitination, restore ATP level and extend lifespan, while blocking autophagy via ATG1 knock-down suppress these effects in aged IFMs. Taken together, these results show that pink1/parkin promotes mitophagy of mitochondrial ubiquitination in aged muscles and extend lifespan in an Atg1-dependent manner. Our study provides physiological evidence that mitophagy of mitochondrial ubiquitination mediated by PINK1/ Parkin is crucial for muscle function and highlights the role of mitophagy in the pathogenesis of chronic diseases like PD.
On Achieving High PHY-Layer Security of D2D-Enabled Heterogeneous Networks

This paper aims to study how to achieve high transmission security in the physical (PHY) layer of a multi-tier heterogeneous network (HetNet) through a simple device-to- device (D2D) enabling scheme. For the HetNet, we propose a simple D2D-enabling scheme with low complexity for users to opportunistically enable their D2D mode and become either D2D or cellular users by exploiting the diversity of all user association signals from all base stations (BSs). To evaluate whether the proposed D2D enabling scheme improves the PHY-layer security of the HetNet, the secrecy outage probability of the HetNet is defined and analyzed from two different perspectives of BSs and users. We define the BS- centric and user-centric security outage events and derive the explicit lower bound on their probability when the proposed D2D enabling scheme is adopted. Our analytical and numerical results not only show that the proposed D2D-enabling scheme can achieve high PHY-layer security but also reveal how densely the BSs should be deployed in the HetNet in order to achieve the high PHY-layer security from the perspectives of BSs and users.
Pathophysiology of Volume Administration in Septic Shock and the Role of the Clinical Pharmacist

Objective: To review physiological rationale and evidence base surrounding fluid harm to prepare the clinical pharmacist for accountability regarding volume-related outcomes. Data Sources: A PubMed/MEDLINE search was conducted using the following terms: (fluid therapy) AND [(critical care) OR (sepsis)] from 1966 to August 2019 published in English. Study Selection and Data Extraction: A total of 3364 citations were reviewed with only relevant clinical data extracted. Data Synthesis: Although early fluid resuscitation may be a necessary component to decrease mortality in the majority of patients with septic shock admitted to the intensive care unit (ICU), the benefit of continued administration after the first 24 hours is uncertain. Paradoxically, a positive fluid balance secondary to intravenous fluid receipt has been associated with diverse and perpetuating detriment on a multitude of organ systems after the first 24 hours of ICU stay. Continued clinical harm has been demonstrated on patient outcomes such as rates of mortality and length of stay. Despite the growing body of evidence supporting the potential adverse aspects of positive fluid balance, fluid overload remains common during critical care admission. Conclusion: Physiological concerns to overly zealous fluid administration and subsequent volume overload are vast. Relevance to Patient Care and Clinical Practice: Optimization of fluid balance in critically ill patients with sepsis is primed for clinical pharmacy intervention. Critical care pharmacists have the potential to improve patient care by optimizing fluid pharmacotherapy while potentially reducing adverse events, days on mechanical ventilation, and length of ICU stay.
Impact of Perinatal Different Intrauterine Environments on Child Growth and Development: Planning and Baseline Data for a Cohort Study

Background Several studies have shown that exposure of the fetus and newborn to prenatal and perinatal events, respectively, may influence the health outcomes of the child throughout their life cycle. Objective This study aimed to increase the knowledge on the impact of different intrauterine environments on child growth and development, as we know that pregnancy and early years are a window of opportunity for health promotion and prevention interventions of diseases. Methods The recruitment occurred 24 to 48 hours after delivery and involved mothers and their newborns in 2 public hospitals in Porto Alegre, Brazil, from December 2011 to January 2016. The mothers-newborns dyads were allocated to 5 groups: diabetes mellitus, mothers with a clinical diagnosis of diabetes; systemic arterial hypertension (SAH), mothers with a clinical diagnosis of systematic arterial hypertensive disease during pregnancy; maternal smoking, mothers who smoked at any moment of gestation; small for gestational age (SGA), mothers with SGA newborns because of intrauterine growth restriction; and control, mothers without the clinical characteristics previously mentioned. Several protocols and anthropometric measurements were applied in the interviews at immediate postpartum and 7 and 15 days and 1, 3, and 6 months after birth. For this study, we analyzed only data collected during postpartum interviews. The statistical analyses were performed using Pearson chi-square test, Mann-Whitney test, or Kruskal-Wallis test with Dunn post hoc. The significance level was set at 5%. The Hospital Ethics and Research Committees approved the study. Results Of the 485 eligible mothers-newborns dyads, 400 agreed to participate (82.5%, 400/485). As expected, newborns from the SGA group had significantly lower birth weight, smaller stature, and lower cephalic perimeter (P<.001). This group also had the highest percentage of primiparous women in comparison with other groups (P=.005) except for control. Mothers from the SAH group had the highest mean age, the highest percentage of cesarean sections, and presented greater gestational weight gain. Conclusions In this study, we describe the planning and structure for the systematic follow-up of mother-newborn dyads in the first 6 months after birth, considering the important demographic and epidemiological transition scenario in Brazil. The results of this prospective longitudinal study may provide a better understanding of the causal mechanisms involved in health and life course disease related to different adverse intrauterine environments.
A Crude Awakening: Effects of Crude Oil on Lipid Metabolism in Calanoid Copepods Terminating Diapause

Calanus finmarchicus and Calanus glacialis are keystone zooplankton species in North Atlantic and Arctic marine ecosystems because they form a link in the trophic transfer of nutritious lipids from phytoplankton to predators on higher trophic levels. These calanoid copepods spend several months of the year in deep waters in a dormant state called diapause, after which they emerge in surface waters to feed and reproduce during the spring phytoplankton bloom. Disruption of diapause timing could have dramatic consequences for marine ecosystems. In the present study, Calanus C5 copepodites were collected in a Norwegian fjord during diapause and were subsequently experimentally exposed to the water-soluble fraction of a naphthenic North Sea crude oil during diapause termination. The copepods were sampled repeatedly while progressing toward adulthood and were analyzed for utilization of lipid stores and for differential expression of genes involved in lipid metabolism. Our results indicate that water-soluble fraction exposure led to a temporary pause in lipid catabolism, suggested by (i) slower utilization of lipid stores in water-soluble fraction-exposed C5 copepodites and (ii) more genes in the β-oxidation pathway being downregulated in water-soluble fraction-exposed C5 copepodites than in the control C5 copepodites. Because lipid content and/or composition may be an important trigger for termination of diapause, our results imply that the timing of diapause termination and subsequent migration to the surface may be delayed if copepods are exposed to oil pollution during diapause or diapause termination. This delay could have detrimental effects on ecosystem dynamics.
Prevalence and risk factors of hypertension, among adults residing in an urban area of North India

Background: The increasing prevalence and severity of hypertens ion with age has acquired the status of an epidemic with long incubation period. It has been associated with various risk factors such as alcoholism, smoking, stress and obesity, wh ich has also started to affect the young population due to modern lifestyle changes. Objectives: To study the prevalence of hypertension and its ri sk factors among adults aged 20 years and above residing in an urban area. Methodology: A cross ‐ sectional study was done among adults ag ed 20 years and above with detailed history and physical examination to evalua te various risk factors associated with hypertension. Results: Out of 957 participants, 53.5% were males, 46.5% we re females. Majority (33.9%) of participants were aged 20 ‐ 29 years and 28.4% had a positive family history of hypertension. Overall prevalence of hypertension was 14.4%. 9.5 % had hypertension stage ‐ 1, 4.9% had hypertension stage ‐ 2, and 11.1% had blood pressur e in pre-hypertension range. Hypertension was also more prevalent in the Upper class (27.7%). Amo ng the participants 33.9% were in the habit of consumption of alcohol, tobacco or both. 14.5 % wer e having mild to moderate self perceived stress. Conclusion: Prevalence of hypertension was more in males compar ed to females because men have more associated risk factors like smoking, alcohol and stress. Hypertensive should be advised for regular health checkups, dietary modifications and life style changes. Regular screening and health education camp and strengthening of health care ser vices are essential for early diagnosis.