Hebron University

About: Hebron University is a education organization based out in Hebron, Palestinian Territory. It is known for research contribution in the topics: Population & Cancer. The organization has 2714 authors who have published 4180 publications receiving 163736 citations.

Islam and management: What can be learned?

Abstract: Religion has a major impact on human behavior, social interactions, and social relations. This research article discusses the impact of Islam on managers' behavior. The impact is exerted from the five pillars of Islam: faith, prayer, alms, fasting, and pilgrimage. From the article, it is evident that such pillars have a direct effect on Moslems' behavior. Besides that, the article shows the significant impact of Allah supreme names on managers' behavior and style. Allah names have a direct interrelationship with management functions like planning, organizing, and directing. A Moslem manager, in fact, can use Allah supreme names as a guide to his management style and action. Finally, the article sheds light on major Islamic management principles and their effect on managers' behavior and perception. © 2006 Wiley Periodicals, Inc.

Cell Cycle Control and HIV-1 Susceptibility Are Linked by CDK6-Dependent CDK2 Phosphorylation of SAMHD1 in Myeloid and Lymphoid Cells

Abstract: Proliferating cells are preferentially susceptible to infection by retroviruses. Sterile α motif and HD domain-containing protein-1 (SAMHD1) is a recently described deoxynucleotide phosphohydrolase controlling the size of the intracellular deoxynucleotide triphosphate (dNTP) pool, a limiting factor for retroviral reverse transcription in noncycling cells. Proliferating (Ki67(+)) primary CD4(+) T cells or macrophages express a phosphorylated form of SAMHD1 that corresponds with susceptibility to infection in cell culture. We identified cyclin-dependent kinase (CDK) 6 as an upstream regulator of CDK2 controlling SAMHD1 phosphorylation in primary T cells and macrophages susceptible to infection by HIV-1. In turn, CDK2 was strongly linked to cell cycle progression and coordinated SAMHD1 phosphorylation and inactivation. CDK inhibitors specifically blocked HIV-1 infection at the reverse transcription step in a SAMHD1-dependent manner, reducing the intracellular dNTP pool. Our findings identify a direct relationship between control of the cell cycle by CDK6 and SAMHD1 activity, which is important for replication of lentiviruses, as well as other viruses whose replication may be regulated by intracellular dNTP availability.

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170

Abstract: We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.

Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy

Abstract: The DNA damage response (DDR) pathway coordinates the identification, signaling, and repair of DNA damage caused by endogenous or exogenous factors and regulates cell-cycle progression with DNA repair to minimize DNA damage being permanently passed through cell division. Severe DNA damage that cannot be repaired may trigger apoptosis; as such, the DDR pathway is of crucial importance as a cancer target. Poly (ADP-ribose) polymerase (PARP) is the best-known element of the DDR, and several PARP inhibitors have been licensed. However, there are approximately 450 proteins involved in DDR, and a number of these other targets are being investigated in the laboratory and clinic. We review the most recent evidence for the clinical effect of PARP inhibition in breast and ovarian cancer and explore expansion into the first-line setting and into other tumor types. We critique the evidence for patient selection techniques and summarize what is known about mechanisms of PARP inhibitor resistance. We then discuss what is known about the preclinical rationale for targeting other members of the DDR pathway and the associated tumor cell genetics that may confer sensitivity to these agents. Examples include DNA damage sensors (MLH1), damage signaling molecules (ataxia-telangiectasia mutated; ataxia-telangiectasia mutated-related and Rad3-related; CHK1/2; DNA-dependent protein kinase, catalytic subunit; WEE1; CDC7), or effector proteins for repair (POLQ [also referred to as POLθ], RAD51, poly [ADP-ribose] glycohydrolase). Early-phase clinical trials targeting some of these molecules, either as a single agent or in combination, are discussed. Finally, we outline the challenges that must be addressed to maximize the therapeutic opportunity that targeting DDR provides.

Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial.

Abstract: Summary Background Many patients who require migraine preventive treatment have not been able to tolerate or have not responded to multiple previous preventive medications. We aimed to assess the safety and efficacy of galcanezumab, an antibody to calcitonin gene-related peptide, in patients with migraine who had not benefited from preventive medications from two to four categories. Methods CONQUER was a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial done at 64 sites (hospitals, clinics, or research centres) in 12 countries (Belgium, Canada, Czech Republic, France, Germany, Hungary, Japan, the Netherlands, South Korea, Spain, the UK, and the USA). Patients were 18–75 years of age, with episodic or chronic migraine, with migraine onset before the age of 50 years, who had a documented failure of preventive medications from two to four drug categories in the past 10 years owing to lack of efficacy or tolerability, or both. Patients were randomised 1:1 to receive subcutaneous placebo or galcanezumab 120 mg per month (with a 240 mg loading dose administered as two 120 mg injections) for 3 months. For masking purposes, patients receiving placebo also received two injections during the first dosing visit. Randomisation was done by a computer-generated random sequence by means of an interactive web-response system stratified by country and migraine frequency (low frequency episodic migraine, four to fewer than eight migraine headache days per month; high frequency episodic migraine, eight to 14 migraine headache days per month and fewer than 15 headache days per month; chronic migraine, at least eight migraine headache days per month and at least 15 headache days per month). The primary endpoint was the overall mean change from baseline in number of monthly migraine headache days during the 3-month treatment period in all patients who were randomly assigned and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , NCT03559257 , and is now completed. Findings Between Sept 10, 2018, and March 21, 2019, 462 participants with episodic (269 [58%]) or chronic (193 [42%]) migraine were randomly assigned and received at least one injection with placebo (n=230) or galcanezumab (n=232). Galcanezumab-treated patients had significantly greater reduction in migraine headache days versus placebo across months 1–3. The galcanezumab group had on average 4·1 fewer monthly migraine headache days compared with baseline (13·4), while the placebo group had on average 1·0 fewer than at baseline (13·0; between-group difference −3·1 [95% CI −3·9 to −2·3]; p Interpretation Galcanezumab was superior to placebo in the preventive treatment of migraine and was safe and well tolerated in patients for whom multiple previous standard-of-care preventive treatments had failed. Galcanezumab might represent an important treatment option for patients who have not benefited from or tolerated previous standard-of-care treatments. Funding Eli Lilly.