Realization of a minimal Kitaev chain in coupled quantum dots.

Majorana bound states constitute one of the simplest examples of emergent non-Abelian excitations in condensed matter physics. A toy model proposed by Kitaev shows that such states can arise at the ends of a spinless p-wave superconducting chain1. Practical proposals for its realization2,3 require coupling neighbouring quantum dots (QDs) in a chain through both electron tunnelling and crossed Andreev reflection4. Although both processes have been observed in semiconducting nanowires and carbon nanotubes5-8, crossed-Andreev interaction was neither easily tunable nor strong enough to induce coherent hybridization of dot states. Here we demonstrate the simultaneous presence of all necessary ingredients for an artificial Kitaev chain: two spin-polarized QDs in an InSb nanowire strongly coupled by both elastic co-tunnelling (ECT) and crossed Andreev reflection (CAR). We fine-tune this system to a sweet spot where a pair of poor man's Majorana states is predicted to appear. At this sweet spot, the transport characteristics satisfy the theoretical predictions for such a system, including pairwise correlation, zero charge and stability against local perturbations. Although the simple system presented here can be scaled to simulate a full Kitaev chain with an emergent topological order, it can also be used imminently to explore relevant physics related to non-Abelian anyons.

Singlet and triplet Cooper pair splitting in hybrid superconducting nanowires.

In most naturally occurring superconductors, electrons with opposite spins form Cooper pairs. This includes both conventional s-wave superconductors such as aluminium, as well as high-transition-temperature, d-wave superconductors. Materials with intrinsic p-wave superconductivity, hosting Cooper pairs made of equal-spin electrons, have not been conclusively identified, nor synthesized, despite promising progress1-3. Instead, engineered platforms where s-wave superconductors are brought into contact with magnetic materials have shown convincing signatures of equal-spin pairing4-6. Here we directly measure equal-spin pairing between spin-polarized quantum dots. This pairing is proximity-induced from an s-wave superconductor into a semiconducting nanowire with strong spin-orbit interaction. We demonstrate such pairing by showing that breaking a Cooper pair can result in two electrons with equal spin polarization. Our results demonstrate controllable detection of singlet and triplet pairing between the quantum dots. Achieving such triplet pairing in a sequence of quantum dots will be required for realizing an artificial Kitaev chain7-9.

Supercurrent in the Presence of Direct Transmission and a Resonant Localized State.

We study the current-phase relation (CPR) of an InSb-Al nanowire Josephson junction in parallel magnetic fields up to 700 mT. At high magnetic fields and in narrow voltage intervals of a gate under the junction, the CPR exhibits π shifts. The supercurrent declines within these gate intervals and shows asymmetric gate voltage dependence above and below them. We detect these features sometimes also at zero magnetic field. The observed CPR properties are reproduced by a theoretical model of supercurrent transport via interference between direct transmission and a resonant localized state.

Sleep-related rhythmic movement disorder in adults - A systematic review with a case report.

Sleep-related rhythmic movement disorder is characterised by stereotyped and repetitive rhythmic movements involving large muscle groups during sleep with frequencies between 0.5 and 2 Hz. Most of the published studies on sleep-related rhythmic movement disorder have focussed on children. Therefore, we performed a systematic review on this topic focussing on the adult population. The review is followed by a case report. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. A total of seven manuscripts (n = 32 individuals) were included in the review. The clinical manifestation of body or head rolling predominated in the majority of included cases (53.13% and 43.75%, respectively). In n = 11 (34.37%) cases, a combination of rhythmic movements was observed. The literature review also revealed a wide spectrum of co-morbidities: insomnia, restless leg syndrome, obstructive sleep apnea, ischaemic stroke, epilepsy, hypertension, alcohol and drug dependency, mild depression, and diabetes mellitus. The case report presented a 33-year-old female who was referred to the sleep laboratory due to a suspicion of sleep bruxism and obstructive sleep apnea. Although the patient was initially suspected of having obstructive sleep apnea and sleep bruxism, after conducting video-polysomnography she met the criteria for sleep-related rhythmic movement disorder as she presented body rolling, which were surprisingly most evident during the rapid eye movement sleep stage. In summary, the prevalence of sleep-related rhythmic movement disorder among adults has not been determined yet. The present review and case report is a good starting point for discussion regarding rhythmic movement disorder in adults and further research on this topic.

Selenoprotein P, peroxiredoxin-5, renalase, and total antioxidant status in patients with suspected obstructive sleep apnea.

PURPOSE: The aim of this study was to investigate the relationship between selenoprotein P, peroxiredoxin-5, renalase, total antioxidant status (TAS), mean blood pressure (mBP), and apnea-hypopnea index (AHI). METHODS: The study group consisted of 112 patients hospitalized to verify the diagnosis of obstructive sleep apnea (OSA). The inclusion criteria were consent to participate in the study and age ≥ 18 years. Patients with active proliferative disease, severe systemic diseases, or mental diseases were excluded from the study. Each patient underwent full polysomnography and had blood pressure measured. Blood samples were collected and laboratory test was performed. RESULTS: Among 112 patients enrolled, there was a statistically significant negative linear correlation between blood pressure values (sBP, dBP, mBP) and selenoprotein P, renalase, and TAS levels. Similarly, there was a negative linear correlation between AHI and selenoprotein P, renalase, and TAS levels, but none between AHI and peroxiredoxin-5. Based on the obtained regression models, higher selenoprotein P, peroxiredoxin-5, and renalase levels were independently associated with higher TAS. Lower mBP values were independently associated with the use of antihypertensive drugs, higher TAS, and younger age. Male gender, higher BMI, and higher mBP were independently associated with higher AHI. CONCLUSIONS: Higher concentrations of selenoprotein P, peroxiredoxin-5, and renalase were associated with higher TAS, which confirms their antioxidant properties. There was an indirect connection between tested antioxidants and blood pressure values.

The clinical characteristic of catathrenia: a new look at an old issue-a systematic review of existing literature.

STUDY OBJECTIVES: The International Classification of Sleep Disorders categorized catathrenia as a respiratory disorder, but there are doubts whether episodes appear during rapid eye movement (REM) sleep or the non-rapid eye movement (NREM), their duration, and symptoms. The main objectives were to identify the most common features and relations of catathrenia. METHODS: PubMed, Embase, and Web of Science were searched according to the PRISMA 2020 guidelines. The Joanna Briggs Institute and the ROBINS-I tools were chosen to assess the risk of bias. RESULTS: A total of 288 records were identified, 31 articles were included. The majority of the studies had a moderate risk of bias. 49.57% of episodes occurred during the NREM sleep, while 46% took place during REM. In 60.34% females, catathrenia was more common in the NREM, while in 59.26% of males was in REM sleep (p < 0.05). Females and obese individuals were found to have shorter episodes (p < 0.05). Age was inversely correlated with minimal episodes duration (r = - 0.34). The continuous positive airway pressure (CPAP) therapy was inversely correlated with the maximal episode duration (r = - 0.48). CONCLUSIONS: Catathrenia occurs with similar frequency in both genders. The most frequent symptoms embraced groaning, awareness of disturbing bedpartners, and daytime somnolence-not confirmed by the Epworth Sleepiness Scale. The episodes occur more frequently in NREM than in REM sleep. Catathrenia may be considered as a sex-specific condition. The effects of CPAP treatment leading to shortening episodes duration, which may indicate the respiratory origin of catathrenia.

Impact of Junction Length on Supercurrent Resilience against Magnetic Field in InSb-Al Nanowire Josephson Junctions.

Semiconducting nanowire Josephson junctions represent an attractive platform to investigate the anomalous Josephson effect and detect topological superconductivity. However, an external magnetic field generally suppresses the supercurrent through hybrid nanowire junctions and significantly limits the field range in which the supercurrent phenomena can be studied. In this work, we investigate the impact of the length of InSb-Al nanowire Josephson junctions on the supercurrent resilience against magnetic fields. We find that the critical parallel field of the supercurrent can be considerably enhanced by reducing the junction length. Particularly, in 30 nm long junctions supercurrent can persist up to 1.3 T parallel field─approaching the critical field of the superconducting film. Furthermore, we embed such short junctions into a superconducting loop and obtain the supercurrent interference at a parallel field of 1 T. Our findings are highly relevant for multiple experiments on hybrid nanowires requiring a magnetic-field-resilient supercurrent.

Performance evaluation of portable respiratory polygraphy for assessing sleep bruxism in adults.

BACKGROUND: Polysomnography (PSG) is the gold standard for sleep bruxism (SB) assessment, it is expensive, not widely accessible, and time-consuming. OBJECTIVE: Given the increasing prevalence of SB, there is a growing need for an alternative, readily available, reliable and cost-effective diagnostic method. This study aimed to evaluate the diagnostic validity of portable respiratory polygraphy (PRPG) compared with PSG for SB diagnosis. METHODS: One hundred and three subjects underwent simultaneous examinations using PRPG (NOX T3, NOX Medical) and PSG (NOX A1, NOX Medical) in a sleep laboratory. RESULTS: The mean Bruxism Episodes Index (BEI) measured by PRPG was 4.70 ± 3.98, whereas PSG yielded a mean BEI of 3.79 ± 3.08. The sensitivity for detecting sleep bruxism (BEI >2) by PRPG was 48.3%, with a specificity of 81.2%. The positive predictive value was estimated at 51.9%, and the negative predictive value at 78.9%. However, when distinguishing between mild bruxism (BEI >2 < 4) and severe bruxism (BEI >4), PRPG demonstrated a sensitivity of 77.8% and 68.3% and a specificity of 48.6% and 71.4%, respectively. CONCLUSION: Polysomnography continues to be the SB diagnostic gold standard tool, as the sensitivity and specificity of PRPG are significantly lower when compared with PSG. Nevertheless, PRPG could serve as an alternative tool for SB screening or diagnosis, despite its limitations. Furthermore, our data indicate that comorbidities such as sleep apnea and sleep quality do not influence the diagnostic accuracy of PSG, suggesting its potential as a screening instrument in individuals with other sleep disorders.

A pleiotropic variant in DNAJB4 is associated with multiple myeloma risk.

Pleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome-wide significant loci shared across cancer and noncancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28 684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P < 5 × 10-8 ) with their respective trait. The selected SNPs were analyzed in 2434 MM cases and 3446 controls from the International Lymphoma Epidemiology Consortium (InterLymph). The 10 SNPs showing the strongest associations with MM risk in InterLymph were selected for replication in an independent set of 1955 MM cases and 1549 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and 418 MM cases and 147 282 controls from the FinnGen project. The combined analysis of the three studies identified an association between DNAJB4-rs34517439-A and an increased risk of developing MM (OR = 1.22, 95%CI 1.13-1.32, P = 4.81 × 10-7 ). rs34517439-A is associated with a modified expression of the FUBP1 gene, which encodes a multifunctional DNA and RNA-binding protein that it was observed to influence the regulation of various genes involved in cell cycle regulation, among which various oncogenes and oncosuppressors. In conclusion, with a pleiotropic scan approach we identified DNAJB4-rs34517439 as a potentially novel MM risk locus.

A case-control study on the effect of rhythmic masticatory muscle activity (RMMA) clusters on sleep fragmentation and severity of orofacial muscle pain in sleep bruxism.

Rhythmic masticatory muscle activity (RMMA) is a periodic muscle activity that characterises sleep bruxism (SB) events. These can occur as a single event, in pairs, or in clusters. Since RMMA episodes often occur in clusters and the relevance of this occurrence is unknown, we conducted a study to investigate the effect of RMMA clusters on sleep fragmentation and the severity of orofacial muscle pain. This study involved a secondary analysis using data from 184 adult subjects with orofacial muscle pain who underwent definitive polysomnography (PSG) for sleep bruxism diagnosis. Self-reported orofacial muscle pain (OFMP) was assessed using the numeric rating scale, and additional evaluation of side-to-side equivalence (symmetry) was described using a binary system. Among the 184 participants, 60.8% (n = 112) did not exhibit clusters and among the 72 participants with clusters, 36.1% (n = 26) and 63.9% (n = 46) were in the high and low RMMA frequency groups, respectively. The high SB group had significantly three times more phasic RMMA events than the noncluster group. A total of 89.67% (n = 165) of subjects reported orofacial muscle pain. While there was no difference in the severity of OFMP among groups, a significant decrease in symmetry between the severity of temporal muscle pain on the left and right sides was noted in the cluster group compared with the noncluster group. Clustering of RMMA events is associated with sleep fragmentation. The asymmetry of temporal muscle pain is related to the presence of RMMA clusters in sleep bruxism.

Is camera recording crucial for the correct diagnosis of sleep bruxism in polysomnography?

Due to potential issues, several sleep laboratories conduct sleep bruxism diagnosis without the use of a camera, instead relying mostly on electromyographic monitoring. The purpose of the study was to determine if a camera is necessary for the polysomnographic evaluation of sleep bruxism and how sleep bruxism parameters change when a camera is not utilised. The study material was actual polysomnographic recordings made in the years 2017-2020. A total of 199 single-night video-polysomnographic recordings of patients who were suspected of having sleep bruxism were chosen at random. The first analysis involved the evaluation of the video recording, while in the second video recording was not used. The findings revealed that all the examined sleep bruxism indices had statistically significantly higher values for the recordings made without the use of a camera. According to the findings, noncamera recordings had decreased sensitivity and specificity when the criteria of bruxism and mild-to-moderate bruxism were taken into account, and decreased sensitivity in the case of the criterion of severe bruxism. Sleep efficiency, the apnea/hypopnea index, and arousals had independent effects on the bruxism episode index value in the analysis of noncamera recordings. In conclusion, camera-based polysomnography still appears to be the most reliable way to assess the severity of sleep bruxism, particularly in patients who also report other sleep disturbances. The presence of symptoms of sleep-disordered breathing, insomnia, or other sleep disorders should prompt us to use camera-based diagnostics.

A Systematic Review of Publications on the Associations Between Sleep Architecture and Arterial Hypertension.

Sleep research has garnered substantial interest among scientists owing to its correlation with various diseases, particularly elevated blood pressure observed in patients with obstructive sleep apnea. This systematic review aims to identify and analyze publications exploring the associations between sleep architecture and arterial hypertension. A comprehensive search of PubMed (MEDLINE), Scopus, and Embase databases yielded 111 reports, of which 7 manuscripts were included in the review. Four of the studies reported a significant reduction in the duration of the N3 phase of sleep in hypertensive patients, while 2 studies found a statistically significant reduction in the duration of the N2 and rapid eye movement (REM) stages of sleep. Three studies indicated increased sleep fragmentation in hypertensive patients. They showed a longer duration of the N1 stage of sleep, shorter duration of overall sleep time, and an increased apnea-hypopnea index in hypertensive patients. These findings underscore the association between the duration of non-REM/REM sleep stages and elevated BP, providing substantial evidence. Moreover, a notable increase in sleep fragmentation was observed among patients with hypertension. However, further research is warranted to expand and deepen our understanding of this intricate relationship. This systematic review serves as a valuable resource, guiding future investigations and contributing to advancements in the field of sleep and arterial hypertension.

Prognostic Potential of Nectin Expressions in Colorectal Cancer: An Exploratory Study.

Colorectal cancer (CRC) is a pressing global health challenge, with an estimated 1.9 million new cases in 2020. Ranking as the third most diagnosed cancer globally, CRC accounts for nearly 930,000 cancer-related deaths annually. Nectins, immunoglobulin-like adhesion molecules, are pivotal in intercellular adhesion formation and cellular function regulation. Altered nectin expression patterns have been identified in various cancers. However, the intricacies of their role in cancer development and progression remain underexplored. This study aimed to evaluate the expression of specific nectins in CRC tumors, explore their association with clinicopathological factors, and ascertain their potential as prognostic indicators for CRC patients post-resection. We retrospectively analyzed the medical records of 92 CRC patients who underwent surgical treatment between 2013 and 2014. Tumor specimens were re-evaluated to determine nectin expression using immunohistochemistry. The study identified heterogeneous expressions of nectin-2, -3, and -4 in 58%, 62.6%, and 87.9% of specimens, respectively. Elevated nectin-4 expression correlated with worse 5-year and overall survival rates, presenting a negative prognostic value (HR = 4, 95% CI: 2.4-6.8, p < 0.001). Conversely, reduced nectin-3 expression was linked to poorer CRC prognosis (HR = 0.54; 95% CI: 0.31-0.96; p = 0.036). Nectin-4 expression positively correlated with elevated carcinoembryonic antigen (CEA) levels and advanced disease stages. In contrast, nectin-3 expression negatively correlated with CEA levels, tumor size, presence of distant metastases, and disease stage. Notably, tumors in the right colon were statistically more likely to express nectin-2 compared to those in the left. This study underscores the potential prognostic significance of nectins in CRC. The high prevalence of nectin-4-expressing cells offers promising avenues for further evaluation in targeted therapeutic interventions with already available agents such as PADCEV.

Coexistence of Cardiovascular Risk Factors and Blood Renalase Concentration.

Cardiovascular diseases (CVDs) are one of the biggest health challenges facing health systems around the world. There are certain risk factors (CVRFs) that contribute to CVD. Risk factors associated with lifestyle such as tobacco consumption are particularly essential. Renalase is a recently discovered flavoprotein that may be involved in the progression of cardiometabolic diseases. The aim of the study was to investigate the relation between CVRFs and blood renalase concentration (BRC). The study group consisted of 96 people (51% women) who were hospitalized in the internal medicine department. CVRFs were measured using the AHA Life 7 scale. The E3109Hu ELISA kit was used to assess BRC. We found higher BRC in groups with a lower number of CVRFs (p < 0.05). We found a negative correlation between BRC and the number of CVRFs (r = -0.41). With the regression analysis, obesity, smoking, and a lack of physical activity (LoPE) were independently associated with lower blood renalase concentration. ROC analysis indicated the highest accuracy of BRC < 38.98 ng/mL in patients with ≥5 CVRFs. In conclusion, patients with a higher number of CVRFs had lower BRCs. The CVRFs particularly associated with a lower BRC were obesity, smoking, and LoPE.

Soluble CD147 (BSG) as a Prognostic Marker in Multiple Myeloma.

CD147 (basigin, BSG) is a membrane-bound glycoprotein involved in energy metabolism that plays a role in cancer cell survival. Its soluble form is a promising marker of some diseases, but it is otherwise poorly studied. CD147 is overexpressed in multiple myeloma (MM) and is known to affect MM progression, while its genetic variants are associated with MM survival. In the present study, we aimed to assess serum soluble CD147 (sCD147) expression as a potential marker in MM. We found that sCD147 level was higher in MM patients compared to healthy individuals. It was also higher in patients with more advanced disease (ISS III) compared to both patients with less advanced MM and healthy individuals, while its level was observed to drop after positive response to treatment. Patients with high sCD147 were characterized by worse progression-free survival. sCD147 level did not directly correlate with bone marrow CD147 mRNA expression. In conclusion, this study suggests that serum sCD147 may be a prognostic marker in MM.

Is sleep bruxism related to the levels of enzymes involved in the serotonin synthesis pathway?

OBJECTIVES: This exploratory research aimed to evaluate the levels of tryptophan hydroxylase 1 (TPH1) and aromatic l-amino acid decarboxylase (DDC), which play an important role in the serotonin synthesis pathway, in individuals with sleep bruxism (SB) diagnosed using audio-video polysomnography (vPSG) and compare them with that of individuals not presenting with SB. MATERIALS AND METHODS: The study included adult patients hospitalized in the Department and Clinic of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology at the Wroclaw Medical University. The participants underwent a single-night vPSG for the evaluation of the SB parameters. Peripheral blood samples were also collected from them for estimating the serum levels of TPH1 and DDC. RESULTS: A total of 105 patients (80 women and 25 men) were included in the study. All the patients were Caucasians and aged 18-63 years (mean age: 33.43 ± 10.8 years). Seventy-five patients (71.43%) presented with SB, of which 50 (47.62%) had severe SB, while the remaining 30 patients (28.57%) did not. No statistically significant differences in TPH1 and DDC levels were observed between the individuals with SB and without SB. A significant negative correlation was found between tonic SB episodes and DDC levels (p = 0.0012). Other correlations between the SB parameters and the levels of the studied enzymes were statistically insignificant (p > 0.05 for all comparisons). CONCLUSIONS: The levels of the enzymes that are crucial for serotonin synthesis (TPH1 and DDC) did not seem to influence SB. CLINICAL RELEVANCE: This study provides important insights for further research on the relationship between the serotonin pathway and SB, which should take into account not only the process of serotonin synthesis but also the effect of serotonin-dependent neurotransmission on SB.

Lower serotonin levels in severe sleep bruxism and its association with sleep, heart rate, and body mass index.

BACKGROUND: Sleep bruxism (SB) is a complex behaviour that seems to be associated with the serotoninergic pathway. OBJECTIVES: This exploratory research aimed to evaluate the levels of serotonin in individuals with sleep bruxism diagnosed by video polysomnography. The study also evaluated whether the levels of serotonin were associated with body mass index, heart rate, and sleep parameters. METHODS: The study participants were adults hospitalised in the Department and Clinic of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology at the Wroclaw Medical University. They underwent a single-night video polysomnography during which sleep and SB parameters and heart rate were evaluated. Additionally, body mass index and blood serotonin levels were evaluated for each patient. RESULTS: A total of 105 patients were included in this study (80 women and 25 men). All the patients were Caucasians aged 18-63 years, with a mean age ± (standard deviation) of 33.43± 10.8 years. Seventy-five patients (71.43%) presented sleep bruxism (bruxism episodes index ≥2) and 30 (28.57%) did not. Fifty patients (47.62%) presented severe sleep bruxism (bruxism episodes index >4). The results showed that lower blood serotonin levels were associated with severe sleep bruxism; increased bruxism episodes index, rapid eye movement sleep, and body mass index; and decreased maximal pulse. CONCLUSION: Severe sleep bruxism and the associated phenomena seem to co-occur with lower blood serotonin levels. The study supports the hypothesis on the relationship between the serotoninergic pathway and sleep bruxism.

The effect of continuous positive airway pressure and mandibular advancement device on sleep bruxism intensity in obstructive sleep apnea patients.

We aimed to evaluate and compare the effects of continuous positive airway pressure (CPAP) and mandibular advancement device (MAD) in reducing the intensity of sleep bruxism (SB) in patients with obstructive sleep apnea (OSA). Forty-eight adults with OSA were subjected to single-night full polysomnography (PSG) in the Sleep Laboratory of the Wroclaw Medical University. The respiratory events and bruxism episodes were scored according to the standards of the American Academy of Sleep Medicine. The patients were assigned to the CPAP treatment or the MAD treatment in accordance to apnea-hypopnea index (AHI). The second PSG examination was conducted during the MAD or CPAP treatment to assess the effect of treatment on bruxism episode index (BEI) and AHI. The mean AHI and mean BEI in the study material were estimated to be 30.05 ± 15.39 and 5.10 ± 5.31, respectively. The bruxism parameters were significantly decreased in both the CPAP and MAD groups. Compared to the MAD, the CPAP treatment was more effective in reducing AHI; however, there was no significant difference in effectiveness of CPAP and MAD treatment in BEI reduction. Both CPAP and MAD treatments were effective against SB coexisting with OSA. Due to the application of these treatment options, the risk of OSA should be estimated in patients with SB.

Do myeloproliferative neoplasms and multiple myeloma share the same genetic susceptibility loci?

Myeloproliferative neoplasms (MPNs) are a group of diseases that cause myeloid hematopoietic cells to overproliferate. Epidemiological and familial studies suggest that genetic factors contribute to the risk of developing MPN, but the genetic susceptibility of MPN is still not well known. Indeed, only few loci are known to have a clear role in the predisposition to this disease. Some studies reported a diagnosis of MPNs and multiple myeloma (MM) in the same patients, but the biological causes are still unclear. We tested the hypothesis that the two diseases share at least partly the same genetic risk loci. In the context of a European multicenter study with 460 cases and 880 controls, we analyzed the effect of the known MM risk loci, individually and in a polygenic risk score (PRS). The most significant result was obtained among patients with chronic myeloid leukemia (CML) for PS0RS1C1-rs2285803, which showed to be associated with an increased risk (OR = 3.28, 95% CI 1.79-6.02, P = .00012, P = .00276 when taking into account multiple testing). Additionally, the PRS showed an association with MPN risk when comparing the last with the first quartile of the PRS (OR = 2.39, 95% CI 1.64-3.48, P = 5.98 × 10-6 ). In conclusion, our results suggest a potential common genetic background between MPN and MM, which needs to be further investigated.

Common gene variants within 3'-untranslated regions as modulators of multiple myeloma risk and survival.

We evaluated the association between germline genetic variants located within the 3'-untranlsated region (polymorphic 3'UTR, ie, p3UTR) of candidate genes involved in multiple myeloma (MM). We performed a case-control study within the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 3056 MM patients and 1960 controls recruited from eight countries. We selected p3UTR of six genes known to act in different pathways relevant in MM pathogenesis, namely KRAS (rs12587 and rs7973623), VEGFA (rs10434), SPP1 (rs1126772), IRF4 (rs12211228) and IL10 (rs3024496). We found that IL10-rs3024496 was associated with increased risk of developing MM and with a worse overall survival of MM patients. The variant allele was assayed in a vector expressing eGFP chimerized with the IL10 3'-UTR and it was found functionally active following transfection in human myeloma cells. In this experiment, the A-allele caused a lower expression of the reporter gene and this was also in agreement with the in vivo expression of mRNA measured in whole blood as reported in the GTEx portal. Overall, these data are suggestive of an effect of the IL10-rs3024496 SNP on the regulation of IL10 mRNA expression and it could have clinical implications for better characterization of MM patients in terms of prognosis.