The role of the histone H3 variant CENPA in prostate cancer.

Overexpression of centromeric proteins has been identified in a number of human malignancies, but the functional and mechanistic contributions of these proteins to disease progression have not been characterized. The centromeric histone H3 variant centromere protein A (CENPA) is an epigenetic mark that determines centromere identity. Here, using an array of approaches, including RNA-sequencing and ChIP-sequencing analyses, immunohistochemistry-based tissue microarrays, and various cell biology assays, we demonstrate that CENPA is highly overexpressed in prostate cancer in both tissue and cell lines and that the level of CENPA expression correlates with the disease stage in a large cohort of patients. Gain-of-function and loss-of-function experiments confirmed that CENPA promotes prostate cancer cell line growth. The results from the integrated sequencing experiments suggested a previously unidentified function of CENPA as a transcriptional regulator that modulates expression of critical proliferation, cell-cycle, and centromere/kinetochore genes. Taken together, our findings show that CENPA overexpression is crucial to prostate cancer growth.

Utility of a Telephone Triage Hotline in Response to the COVID-19 Pandemic: Longitudinal Observational Study.

BACKGROUND: During the initial months of the COVID-19 pandemic, rapidly rising disease prevalence in the United States created a demand for patient-facing information exchanges that addressed questions and concerns about the disease. One approach to managing increased patient volumes during a pandemic involves the implementation of telephone-based triage systems. During a pandemic, telephone triage hotlines can be employed in innovative ways to conserve medical resources and offer useful population-level data about disease symptomatology and risk factor profiles. OBJECTIVE: The aim of this study is to describe and evaluate the COVID-19 telephone triage hotline used by a large academic medical center in the midwestern United States. METHODS: Michigan Medicine established a telephone hotline to triage inbound patient calls related to COVID-19. For calls received between March 24, 2020, and May 5, 2020, we described total call volume, data reported by callers including COVID-19 risk factors and symptomatology, and distribution of callers to triage algorithm endpoints. We also described symptomatology reported by callers who were directed to the institutional patient portal (online medical visit questionnaire). RESULTS: A total of 3929 calls (average 91 calls per day) were received by the call center during the study period. The maximum total number of daily calls peaked at 211 on March 24, 2020. Call volumes were the highest from 6 AM to 11 AM and during evening hours. Callers were most often directed to the online patient portal (1654/3929, 42%), nursing hotlines (1338/3929, 34%), or employee health services (709/3929, 18%). Cough (126/370 of callers, 34%), shortness of breath (101/370, 27%), upper respiratory infection (28/111, 25%), and fever (89/370, 24%) were the most commonly reported symptoms. Immunocompromised state (23/370, 6%) and age >65 years (18/370, 5%) were the most commonly reported risk factors. CONCLUSIONS: The triage algorithm successfully diverted low-risk patients to suitable algorithm endpoints, while directing high-risk patients onward for immediate assessment. Data collected from hotline calls also enhanced knowledge of symptoms and risk factors that typified community members, demonstrating that pandemic hotlines can aid in the clinical characterization of novel diseases.

Rapid molecular assays to study human centromere genomics.

The centromere is the structural unit responsible for the faithful segregation of chromosomes. Although regulation of centromeric function by epigenetic factors has been well-studied, the contributions of the underlying DNA sequences have been much less well defined, and existing methodologies for studying centromere genomics in biology are laborious. We have identified specific markers in the centromere of 23 of the 24 human chromosomes that allow for rapid PCR assays capable of capturing the genomic landscape of human centromeres at a given time. Use of this genetic strategy can also delineate which specific centromere arrays in each chromosome drive the recruitment of epigenetic modulators. We further show that, surprisingly, loss and rearrangement of DNA in centromere 21 is associated with trisomy 21. This new approach can thus be used to rapidly take a snapshot of the genetics and epigenetics of each specific human centromere in nondisjunction disorders and other biological settings.

Mapping the travel patterns of people with malaria in Bangladesh.

BACKGROUND: Spread of malaria and antimalarial resistance through human movement present major threats to current goals to eliminate the disease. Bordering the Greater Mekong Subregion, southeast Bangladesh is a potentially important route of spread to India and beyond, but information on travel patterns in this area are lacking. METHODS: Using a standardised short survey tool, 2090 patients with malaria were interviewed at 57 study sites in 2015-2016 about their demographics and travel patterns in the preceding 2 months. RESULTS: Most travel was in the south of the study region between Cox's Bazar district (coastal region) to forested areas in Bandarban (31% by days and 45% by nights), forming a source-sink route. Less than 1% of travel reported was between the north and south forested areas of the study area. Farmers (21%) and students (19%) were the top two occupations recorded, with 67 and 47% reporting travel to the forest respectively. Males aged 25-49 years accounted for 43% of cases visiting forests but only 24% of the study population. Children did not travel. Women, forest dwellers and farmers did not travel beyond union boundaries. Military personnel travelled the furthest especially to remote forested areas. CONCLUSIONS: The approach demonstrated here provides a framework for identifying key traveller groups and their origins and destinations of travel in combination with knowledge of local epidemiology to inform malaria control and elimination efforts. Working with the NMEP, the findings were used to derive a set of policy recommendations to guide targeting of interventions for elimination.

Sulfone-Mediated SNAr Reaction as a Powerful Tool for the Synthesis of 4-Quinolinyl Ethers and More-Application to the Synthesis of HCV NS3/4a Protease Inhibitor BI 201420.

An efficient general methodology for the synthesis of 4-quinolinyl ethers is demonstrated via a highly reactive SNAr reaction of 4-quinolinyl sulfones with a range of structurally diversified 1°, 2°, and 3° alcohols with a wide substrate scope and high yields. By adapting this methodology, a convergent synthesis of a complex target of HCV NS3/4a protease inhibitor BI 201420 was accomplished.

Mapping the stability of malaria hotspots in Bangladesh from 2013 to 2016.

BACKGROUND: Malaria claims hundreds of thousands of lives each year, most of them children. A "malaria-free world" is the World Health Organization's vision, but elimination from the southeast Asian Region is hampered by factors including anti-malarial resistance and systematic underreporting. Malaria is a significant public health problem in Bangladesh and while there have been recent gains in control, there is large spatial and temporal heterogeneity in the disease burden. This study aims to determine the pattern and stability of malaria hotspots in Bangladesh with the end goal of informing intervention planning for elimination. RESULTS: Malaria in Bangladesh exhibited highly seasonal, hypoendemic transmission in geographic hotspots, which remained conserved over time. The southeast areas of the Chittagong Hill Tracts were identified as malaria hotspots for all 4 years examined. Similarly, areas in Sunamganj and Netrakona districts in the Northeast were hotspots for 2013-2016. Highly stable hotspots from 1 year predicted the following year's hotspot locations in the southeast of Bangladesh. Hotspots did not appear to act as sources of spread with no evidence of consistent patterns of contiguous spread or recession of hotspots as high or low transmission seasons progressed. CONCLUSIONS: Areas were identified with temporal and spatial clustering of high malaria incidence in Bangladesh. Further studies are required to understand the vector, sociodemographic and disease dynamics within these hotspots. Given the low caseloads occurring in the low transmission seasons, and the conserved nature of malaria hotspots, directing resources towards these areas may be an efficient way to achieve malaria elimination in Bangladesh.

Intercellular trafficking of the nuclear oncoprotein DEK.

DEK is a biochemically distinct, conserved nonhistone protein that is vital to global heterochromatin integrity. In addition, DEK can be secreted and function as a chemotactic, proinflammatory factor. Here we show that exogenous DEK can penetrate cells, translocate to the nucleus, and there carry out its endogenous nuclear functions. Strikingly, adjacent cells can take up DEK secreted from synovial macrophages. DEK internalization is a heparan sulfate-dependent process, and cellular uptake of DEK into DEK knockdown cells corrects global heterochromatin depletion and DNA repair deficits, the phenotypic aberrations characteristic of these cells. These findings thus unify the extracellular and intracellular activities of DEK, and suggest that this paracrine loop involving DEK plays a role in chromatin biology.

Regulation of the human endogenous retrovirus K (HML-2) transcriptome by the HIV-1 Tat protein.

UNLABELLED: Approximately 8% of the human genome is made up of endogenous retroviral sequences. As the HIV-1 Tat protein activates the overall expression of the human endogenous retrovirus type K (HERV-K) (HML-2), we used next-generation sequencing to determine which of the 91 currently annotated HERV-K (HML-2) proviruses are regulated by Tat. Transcriptome sequencing of total RNA isolated from Tat- and vehicle-treated peripheral blood lymphocytes from a healthy donor showed that Tat significantly activates expression of 26 unique HERV-K (HML-2) proviruses, silences 12, and does not significantly alter the expression of the remaining proviruses. Quantitative reverse transcription-PCR validation of the sequencing data was performed on Tat-treated PBLs of seven donors using provirus-specific primers and corroborated the results with a substantial degree of quantitative similarity. IMPORTANCE: The expression of HERV-K (HML-2) is tightly regulated but becomes markedly increased following infection with HIV-1, in part due to the HIV-1 Tat protein. The findings reported here demonstrate the complexity of the genome-wide regulation of HERV-K (HML-2) expression by Tat. This work also demonstrates that although HERV-K (HML-2) proviruses in the human genome are highly similar in terms of DNA sequence, modulation of the expression of specific proviruses in a given biological situation can be ascertained using next-generation sequencing and bioinformatics analysis.

Concise review: role of DEK in stem/progenitor cell biology.

Understanding the factors that regulate hematopoiesis opens up the possibility of modifying these factors and their actions for clinical benefit. DEK, a non-histone nuclear phosphoprotein initially identified as a putative proto-oncogene, has recently been linked to regulate hematopoiesis. DEK has myelosuppressive activity in vitro on proliferation of human and mouse hematopoietic progenitor cells and enhancing activity on engraftment of long-term marrow repopulating mouse stem cells, has been linked in coordinate regulation with the transcription factor C/EBPα, for differentiation of myeloid cells, and apparently targets a long-term repopulating hematopoietic stem cell for leukemic transformation. This review covers the uniqueness of DEK, what is known about how it now functions as a nuclear protein and also as a secreted molecule that can act in paracrine fashion, and how it may be regulated in part by dipeptidylpeptidase 4, an enzyme known to truncate and modify a number of proteins involved in activities on hematopoietic cells. Examples are provided of possible future areas of investigation needed to better understand how DEK may be regulated and function as a regulator of hematopoiesis, information possibly translatable to other normal and diseased immature cell systems.

Synthesis of phosphaguanidines by hydrophosphination of carbodiimides with phosphine boranes.

The direct addition of anionic secondary phosphine boranes to carbodiimides yields both chiral and achiral phosphaguanidine boranes under ambient temperature conditions. An analogous preparation of menthol-derived phosphinite boranes is also described. These products can be deborinated to give the corresponding phosphines, and subsequently oxidized to give phosphine oxides. The robustness of this method was further demonstrated in the synthesis of structurally novel cyclic phosphaguanidines.

Centromere defects, chromosome instability, and cGAS-STING activation in systemic sclerosis.

Centromere defects in Systemic Sclerosis (SSc) have remained unexplored despite the fact that many centromere proteins were discovered in patients with SSc. Here we report that lesion skin fibroblasts from SSc patients show marked alterations in centromeric DNA. SSc fibroblasts also show DNA damage, abnormal chromosome segregation, aneuploidy (only in diffuse cutaneous (dcSSc)) and micronuclei (in all types of SSc), some of which lose centromere identity while retaining centromere DNA sequences. Strikingly, we find cytoplasmic "leaking" of centromere proteins in limited cutaneous SSc (lcSSc) fibroblasts. Cytoplasmic centromere proteins co-localize with antigen presenting MHC Class II molecules, which correlate precisely with the presence of anti-centromere antibodies. CENPA expression and micronuclei formation correlate highly with activation of the cGAS-STING/IFN-ß pathway as well as markers of reactive oxygen species (ROS) and fibrosis, ultimately suggesting a link between centromere alterations, chromosome instability, SSc autoimmunity, and fibrosis.

Assessment of Plasmodium falciparum Artemisinin Resistance Independent of kelch13 Polymorphisms and with Escalating Malaria in Bangladesh.

Emerging resistance to artemisinin drugs threatens the elimination of malaria. Resistance is widespread in South East Asia (SEA) and Myanmar. Neighboring Bangladesh, where 90% of infections occur in the Chittagong Hill Tracts (CHTs), lacks recent assessment. We undertook a prospective study in the sole district-level hospital in Bandarban, a CHT district with low population densities but 60% of reported malaria cases. Thirty patients presented with malaria in 2018. An increase to 68 patients in 2019 correlated with the district-level rise in malaria, rainfall, humidity, and temperature. Twenty-four patients (7 in 2018 and 17 in 2019) with uncomplicated Plasmodium falciparum monoinfection were assessed for clearing parasites after starting artemisinin combination therapy (ACT). The median (range) time to clear half of the initial parasites was 5.6 (1.5 to 9.6) h, with 20% of patients showing a median of 8 h. There was no correlation between parasite clearance and initial parasitemia, blood cell counts, or mutations of P. falciparum gene Pfkelch13 (the molecular marker of artemisinin resistance [AR]). The in vitro ring-stage survival assay (RSA) revealed one (of four) culture-adapted strains with a quantifiable resistance of 2.01% ± 0.1% (mean ± standard error of the mean [SEM]). Regression analyses of in vivo and in vitro measurements of the four CHT strains and WHO-validated K13 resistance mutations yielded good correlation (R2 = 0.7; ρ = 0.9, P < 0.005), strengthening evaluation of emerging AR with small sample sizes, a challenge in many low/moderate-prevalence sites. There is an urgent need to deploy multiple, complementary approaches to understand the evolutionary dynamics of the emergence of P. falciparum resistant to artemisinin derivatives in countries where malaria is endemic. IMPORTANCE Malaria elimination is a Millennium Development Goal. Artemisinins, fast-acting antimalarial drugs, have played a key role in malaria elimination. Emergence of artemisinin resistance threatens the global elimination of malaria. Over the last decade, advanced clinical and laboratory methods have documented its spread throughout South East Asia and Myanmar. Neighboring Bangladesh lies in the historical path of dissemination of antimalarial resistance to the rest of the world, yet it has not been evaluated by combinations of leading methods, particularly in the highland Chittagong Hill Tracts adjacent to Myanmar which contain >90% of malaria in Bangladesh. We show the first establishment of capacity to assess clinical artemisinin resistance directly in patients in the hilltops and laboratory adaptation of Bangladeshi parasite strains from a remote, sparsely populated malaria frontier that is responsive to climate. Our study also provides a generalized model for comprehensive monitoring of drug resistance for countries where malaria is endemic.

Comparing Clinical Features and Outcomes in Mechanically Ventilated Patients with COVID-19 and Acute Respiratory Distress Syndrome.

Rationale: Patients with severe coronavirus disease (COVID-19) meet clinical criteria for the acute respiratory distress syndrome (ARDS), yet early reports suggested they differ physiologically and clinically from patients with non-COVID-19 ARDS, prompting treatment recommendations that deviate from standard evidence-based practices for ARDS. Objectives: To compare respiratory physiology, clinical outcomes, and extrapulmonary clinical features of severe COVID-19 with non-COVID-19 ARDS. Methods: We performed a retrospective cohort study, comparing 130 consecutive mechanically ventilated patients with severe COVID-19 with 382 consecutive mechanically ventilated patients with non-COVID-19 ARDS. Initial respiratory physiology and 28-day outcomes were compared. Extrapulmonary manifestations (inflammation, extrapulmonary organ injury, and coagulation) were compared in an exploratory analysis. Results: Comparison of patients with COVID-19 and non-COVID-19 ARDS suggested small differences in respiratory compliance, ventilatory efficiency, and oxygenation. The 28-day mortality was 30% in patients with COVID-19 and 38% in patients with non-COVID-19 ARDS. In adjusted analysis, point estimates of differences in time to breathing unassisted at 28 days (adjusted subdistributional hazards ratio, 0.98 [95% confidence interval (CI), 0.77-1.26]) and 28-day mortality (risk ratio, 1.01 [95% CI, 0.72-1.42]) were small for COVID-19 versus non-COVID-19 ARDS, although the confidence intervals for these estimates include moderate differences. Patients with COVID-19 had lower neutrophil counts but did not differ in lymphocyte count or other measures of systemic inflammation. Conclusions: In this single-center cohort, we found no evidence for large differences between COVID-19 and non-COVID-19 ARDS. Many key clinical features of severe COVID-19 were similar to those of non-COVID-19 ARDS, including respiratory physiology and clinical outcomes, although our sample size precludes definitive conclusions. Further studies are needed to define COVID-19-specific pathophysiology before a deviation from evidence-based treatment practices can be recommended.

Association of Urinary MyProstateScore, Age, and Prostate Volume in a Longitudinal Cohort of Healthy Men: Long-term Findings from the Olmsted County Study.

BACKGROUND: Serum prostate-specific antigen (PSA), used in prostate cancer screening, is nonspecific for cancer and is affected by age and prostate volume. More specific biomarkers could be more accurate for early detection of prostate cancer and reduce unnecessary prostate biopsies. OBJECTIVE: To evaluate the association of age and prostate volume with urinary MyProstateScore (MPS) in a screened, longitudinal cohort without evidence of prostate cancer. DESIGN SETTING AND PARTICIPANTS: The Olmsted County Study included men aged 40-79 yr who underwent biennial prostate cancer screening. PSA ≥4.0 ng/ml or abnormal rectal examination triggered prostate biopsy, and patients with cancer were excluded. The remaining men submitted urinary specimens for PCA3 and TMPRSS2:ERG testing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: MPS was calculated using the validated, locked model for grade group ≥2 cancer that includes serum PSA, urinary PCA3, and urinary TMPRSS2:ERG. The associations of age and volume with biomarkers were assessed in multivariable regression models. The t statistic was used to quantify the strength of associations independent of the unit of measurement, and R 2 values were used to estimate the proportion of biomarker variance explained by each factor. RESULTS AND LIMITATIONS: The study included 314 screened men without evidence of cancer. In multivariable models including age and volume, PCA3 score was significantly associated with age (t = 7.51; p < 0.001), while T2:ERG score was not associated with age or volume. MPS was significantly associated with both age (t = 7.45; p < 0.001) and volume (t = 3.56; p < 0.001), but accounting for age alone explained the variability observed (R 2 = 0.29) in a similar way to the model including age and volume (R 2 = 0.31). The variability of PCA3, T2:ERG, and MPS was less dependent on age and volume than the variability for PSA (R 2 = 0.45). CONCLUSIONS: In a cohort of longitudinally screened men without evidence of cancer, we found that MPS demonstrated less variability with noncancer factors (age, prostate volume) than PSA did. These findings support the biology of these markers as more cancer-specific than PSA and highlight their promise in reducing the morbidity associated with PSA-based screening. PATIENT SUMMARY: In a group of men with no evidence of prostate cancer, we found that each of three urine-based markers of cancer-PCA3, T2:ERG, and the commercially available MyProstateScore test-showed less variability with noncancer factors (age and prostate volume) than serum PSA (prostate-specific antigen) did. These findings support their proposed use as noninvasive markers of prostate cancer that could improve the accuracy of early detection.

Large-scale asymmetric synthesis of a cathepsin S inhibitor.

A potent reversible inhibitor of the cysteine protease cathepsin-S was prepared on large scale using a convergent synthetic route, free of chromatography and cryogenics. Late-stage peptide coupling of a chiral urea acid fragment with a functionalized aminonitrile was employed to prepare the target, using 2-hydroxypyridine as a robust, nonexplosive replacement for HOBT. The two key intermediates were prepared using a modified Strecker reaction for the aminonitrile and a phosphonation-olefination-rhodium-catalyzed asymmetric hydrogenation sequence for the urea. A palladium-catalyzed vinyl transfer coupled with a Claisen reaction was used to produce the aldehyde required for the side chain. Key scale up issues, safety calorimetry, and optimization of all steps for multikilogram production are discussed.

Evaluation of the Effectiveness of Screening for Iliac Arterial Calcification in Kidney Transplant Candidates.

BACKGROUND Peripheral vascular disease and iliac arterial calcification are prevalent in kidney transplant candidates and jeopardize graft outcomes. We report our experience with computed tomography (CT) screening for iliac arterial calcification. MATERIAL AND METHODS We retrospectively reviewed electronic medical records of 493 renal transplant candidates from protocol initiation in 2014. Non-contrast CT was performed or retrospectively reviewed if any of the following criteria were present: diabetes, ESRD >6 years, 25 pack-years of smoking or current smoker, diagnosis of peripheral vascular disease, parathyroidectomy, and coronary artery disease intervention. Differences in evaluation and transplant outcomes between groups were compared with chi-squared analysis. Multivariate logistic regression identified predictive criteria for presence of iliac arterial calcification. RESULTS Of 493 candidates evaluated, CTs were reviewed in 346 (70.2%). Iliac arterial calcification was identified in 119 screened candidates (34.4%). Of candidates with iliac arterial calcification identified on CT, 16 (13.4%) were excluded for CT findings, and 9 (7.6%) had their surgical management plan changed. Overall, 91 (76.5%) candidates with iliac arterial calcification on CT were approved, compared to 203 (89.4%) without calcification (P<0.001). The percentage of screened patients with iliac arterial calcification on CT increased with increasing age (P<0.0005). Age and diabetes mellitus were predictive of calcification. CONCLUSIONS Many kidney transplant candidates are at risk for iliac arterial calcification, although such calcification does not prevent transplantation for most candidates who have it. Algorithmic pre-operative screening has clinical value in determining transplant candidacy and potentially improving postoperative outcomes in patients requiring kidney transplantation.

Imputing HbA1c from capillary blood glucose levels in patients with type 2 diabetes in Sri Lanka: a cross-sectional study.

OBJECTIVE: To develop a population-specific methodology for estimating glycaemic control that optimises resource allocation for patients with diabetes in rural Sri Lanka. DESIGN: Cross-sectional study. SETTING: Trincomalee, Sri Lanka. PARTICIPANTS: Patients with non-insulin-treated type 2 diabetes (n=220) from three hospitals in Trincomalee, Sri Lanka. OUTCOME MEASURE: Cross-validation was used to build and validate linear regression models to identify predictors of haemoglobin A1c (HbA1c). Validation of models that regress HbA1c on known determinants of glycaemic control was thus the major outcome. These models were then used to devise an algorithm for categorising the patients based on estimated levels of glycaemic control. RESULTS: Time since last oral intake other than water and capillary blood glucose were the statistically significant predictors of HbA1c and thus included in the final models. In order to minimise type II error (misclassifying a high-risk individual as low-risk or moderate-risk), an algorithm for interpreting estimated glycaemic control was created. With this algorithm, 97.2% of the diabetic patients with HbA1c ≥9.0% were correctly identified. CONCLUSIONS: Our calibrated algorithm represents a highly sensitive approach for detecting patients with high-risk diabetes while optimising the allocation of HbA1c testing. Implementation of these methods will optimise the usage of resources devoted to the management of diabetes in Trincomalee, Sri Lanka. Further external validation with diverse patient populations is required before applying our algorithm more widely.

Rational Design of New Dihydrobenzooxophosphole-Based Lewis Base Organocatalysts.

A series of new dihydrobenzooxophosphole-based Lewis Base organocatalysts were designed and synthesized. They are demonstrated effective in trichlorosilane-mediated stereoselective conjugate reductions of C=C bonds. DFT calculations reveal that the strong hydrogen bond between the amide linker and the chloride on silicon in the transition state contributes to the high reactivity of the catalyst 3a.

Epidemiology of Imported Malaria in Netrokona District of Bangladesh 2013-2018: Analysis of Surveillance Data.

INTRODUCTION: Netrokona is one of the first phase malaria elimination targeted 8 districts of Bangladesh by 2021. The district constitutes only 7% of the population but contributes half of the malaria cases in that area. Most of the cases of that district are imported from Meghalaya State of India. The study was conducted to understand the epidemiology of these imported malaria cases for further strategy development to prevent both imported and introduced cases. METHODOLOGY: The study was retrospectively conducted on the malaria cases confirmed by microscopy and/or RDT by the government and/or NGO service providers between 2013 and 2018. The information of the cases was collected from the verbal "investigation" report of individual malaria confirmed cases. The respondents of the "investigation" were either the patients or their family members. Out of the 713 cases during the study period, descriptive analysis of 626 cases (based on the completeness of "investigation form") of the district was done using MS Excel version 2016. RESULTS: Proportion of imported malaria in Netrokona district increased from 60% in 2013 to 95% in 2018 which persists throughout the year with a little seasonal fluctuation. The overall contribution of these imported cases is 93% by cross-border workers by population type and 84%, 66%, and 95% by male, labour, and tribal population considering the factors of sex, occupation, and ethnicity, respectively. Population aged between 15 and 49 years contributed 82% of these imported cases. All of these cases occurred in the internationally bordering belt with Meghalaya State of India. Species-wise distribution revealed lower P. falciparum (63%) and higher mixed (28%) infection in imported cases compared to the 71% Pf and 20% mixed infection among the indigenous infections whereas P. vivax is similar in both cases. CONCLUSION: Imported malaria is an emerging issue that has a potential risk of increased local transmission which might be a challenge to malaria elimination in that area. Appropriate interventions targeting the cross-border workers are essential to prevent the introduced cases and subsequently avoid reestablishment when elimination of the disease is achieved.

The Genomic Landscape of Centromeres in Cancers.

Centromere genomics remain poorly characterized in cancer, due to technologic limitations in sequencing and bioinformatics methodologies that make high-resolution delineation of centromeric loci difficult to achieve. We here leverage a highly specific and targeted rapid PCR methodology to quantitatively assess the genomic landscape of centromeres in cancer cell lines and primary tissue. PCR-based profiling of centromeres revealed widespread heterogeneity of centromeric and pericentromeric sequences in cancer cells and tissues as compared to healthy counterparts. Quantitative reductions in centromeric core and pericentromeric markers (α-satellite units and HERV-K copies) were observed in neoplastic samples as compared to healthy counterparts. Subsequent phylogenetic analysis of a pericentromeric endogenous retrovirus amplified by PCR revealed possible gene conversion events occurring at numerous pericentromeric loci in the setting of malignancy. Our findings collectively represent a more comprehensive evaluation of centromere genetics in the setting of malignancy, providing valuable insight into the evolution and reshuffling of centromeric sequences in cancer development and progression.