Outcomes of central nervous system tuberculosis in Saudi Arabia: a multi-center study.

OBJECTIVES: Central nervous system tuberculosis (TB) (CNS-TB) can occur in several forms, including intracranial tuberculoma, tuberculous brain abscess, TB meningitis (TBM), and spinal TB. Early treatment can save lives and prevent severe neurological complications. This study aimed to describe the characteristics and post-treatment outcomes of patients with CNS-TB and identify factors associated with poor outcomes. To the best of our knowledge, this is the largest CNS-TB study till date published in Saudi Arabia. METHODS: This retrospective cohort study included all patients diagnosed with CNS-TB in three tertiary centers in Saudi Arabia (King Abdulaziz Medical City in Jeddah, King Abdulaziz Medical City in Riyadh, and Al-Noor Specialist Hospital in Makkah) between 2009 and 2019. Data of patients' demographics, co-morbidities, presenting symptoms, type of CNS-TB, medical and surgical treatments, and outcome after completion of treatment were obtained from medical records. Treatment outcomes were categorized using the modified Rankin Scale for neurological disability. RESULTS: A total of 140 participants were included in this study from 2009 to 2019. Good outcomes were achieved in approximately 65% of cases, whereas 35% had poor outcomes based on the modified Rankin Scale. Glasgow Coma Scale score ≤10 at presentation and TBM/tuberculoma were significantly associated with poor outcomes. Moreover, the use of corticosteroids, more than three anti-TB medications, and surgical interventions were not significantly associated with good or poor outcomes. DISCUSSION: CNS-TB is associated with a high burden of long-term neurological morbidity. Early detection and treatment are crucial to prevent serious complications and decrease morbidity and mortality.

Clinical and Radiological Features of Unilateral Posterior Reversible Encephalopathy Syndrome (PRES): A Case Report.

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity characterized by reversible vasogenic edema predominantly affecting the posterior regions of the cerebral hemispheres. However, unilateral presentation of PRES is an exceptionally rare manifestation. We describe the case of a 34-year-old woman who presented with left-sided hemiparesis, hemisensory loss, headache, and focal motor seizures. Brain CT revealed right anterior and posterior hypodensities in the right frontal and parietal subcortical locations, brain MRI showed vasogenic edema in the subcortical right cerebral hemisphere, and cerebral angiogram revealed diffuse narrowing of the left internal carotid artery just distal to the carotid bifurcation with no flow of contrast beyond the ophthalmic segment. The patient's symptoms resolved during her admission, MRI findings improved on repeated imaging, and she was ultimately diagnosed with unilateral PRES. Unilateral PRES is a complex and challenging diagnosis, and this case sheds light on the atypical radiological features of unilateral PRES possibly intricately linked with contralateral steno-occlusive disease of the carotid artery. It is essential to maintain the atypical variants of PRES as part of the differential diagnosis when encountering acute neurological symptoms and vasogenic edema on imaging in the context of contralateral steno-occlusive disease of the carotid artery.

'One Is Too Many' preventing self-harm and suicide in military veterans: a quantitative evaluation.

INTRODUCTION: In 2021, the Armed Forces Covenant Fund Trust allocated over £2 million to programmes designed to have a clear and demonstrable impact on suicide prevention. Four grant holders delivered a combination of psychotherapeutic interventions, group activities, social prescribing, peer support mentoring, life skills coaching, educational courses and practical help with housing and employment. The evaluation was completed between August 2021 and July 2023. METHODS: A survey was completed by 503 participants at entry and 423 at exit. It captured data regarding demographic and military-specific details, health status, situational stressors, predisposing symptoms, help-seeking behaviour, social engagement, housing, living arrangements and employment status. The questionnaire included a number of validated psychometric questionnaires. RESULTS: This evaluation revealed reductions in situational stressors, symptoms and mental health illnesses. Seventy-six per cent of participants had completed an Operational Tour, and 77% were exposed to a traumatic event during service. It was the negative impact of unresolved traumatic effects that influenced service-users to require support. Forty-nine per cent delayed seeking help, and 36% self-referred to the One Is Too Many programme which demonstrates the importance of this option. There were improvements in the participants' social networking, social activities, club membership and having people to rely on. Only 4% of participants were women which reinforces the requirement to explore initiatives to engage with female veterans. CONCLUSIONS: Timely therapeutic and social prescribing interventions in a safe environment lowered depression, anxiety and the associated situational stressors leading to self-harming and may have reduced suicide. It presented another option to veterans and their families regarding where they can obtain support, care and therapeutic interventions. The programme provided a strong foundation for delivery organisations to forge lasting collaborative partnerships that can be extended to working with other authorities and institutes. The results highlight pathways for prevention and intervention strategies to inform policymakers, healthcare professionals and third-sector organisations.

Epidemiological insights into paratuberculosis in camels in Saudi Arabia: Bayesian estimation of true prevalence and identification of risk factors.

Paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a significant concern in the camel population of Saudi Arabia. This study aimed to provide epidemiological insights into the disease by estimating the true prevalence in camels in the Eastern Province and Riyadh, using a Bayesian estimation framework, and exploring the associated risk factors through a frequentist approach. A total of 1200 camel blood samples were collected and analyzed using an indirect ELISA method. The true herd-level prevalence was estimated at 0.7 (95% probability interval: 0.57 to 0.81), and the mean expected true animal-level prevalence was 0.17 (0.14 to 0.20). Risk factors associated with Map seropositivity were identified, including sex, breed, raising system, and production type. Females, single breed camels, and nomadic raising systems were found to have lower odds of seropositivity, while camels used for racing and show had significantly higher odds. The study's Bayesian approach, adjusting for the imperfect accuracy of MAP tests, provides a nuanced understanding of the disease's prevalence in the region. The integration of true prevalence estimates with risk factor analysis offers a comprehensive framework that can guide future policies and strategies in the fight against paratuberculosis in Saudi Arabia. The findings emphasize the importance of targeted control measures, underscoring the urgent need for interventions in Saudi Arabia's camel population. By understanding the true disease prevalence and its associated risk factors, we can enhance disease management strategies, offering valuable insights for future control and eradication efforts in the region.

Innate and adaptive immune responses in the intestine of camel (Camelus dromedarius) naturally infected with Mycobacterium avium subspecies paratuberculosis.

The spread of John's disease in camel herds (Camelus dromedarius) has been worldwide reported. Despite extensive studies on Mycobacterium avium subspecies paratuberculosis (MAP) infection in camels, the complete pathogenesis and epidemiology of this infection have not been fully exploited. The objective of the study is focusing on the nature of the immune responses, and the types of the recruited cells were studied in the intestine of naturally infected camels employing immunohistochemistry to analyze the expression of CD335, CD103, CD11b, and CD38 markers. Marked expression of some or all of the markers was observed in the ileum, mesenteric, and supramammary lymph nodes of the old infected camels. The expression of CD335, a well-known natural killer (NK) cell marker, was detected in the mesenteric lymph node, while the dendritic cell (DCs) marker, CD103, was markedly expressed in the villi and propria submucosa (PS) of the ileum in old infected camels. CD103 + and CD11b + DCs were detected in the mesenteric lymph nodes of young infected camels. The expression of CD38, a crucial proinflammatory marker, was more noticeable in the peripheral region of the mesenteric lymph node. The expression of these markers in the infected camel intestine was peculiar and is reported for the first time. In summary, the unique expression patterns of CD335, CD103, CD11b, and CD38 markers in naturally infected camel intestines revealed through immunohistochemistry new insights into the immune responses associated with MAP infection. These first-time observations suggest potential roles of innate and adaptive immunity, highlighting specific aspects of MAP immunopathology. Further studies with targeted tools are crucial for a precise understanding of these markers' roles in the infected intestines.

Palindromic Rheumatism Improved After Bariatric Surgery: A Case Report.

Palindromic rheumatism (PR) is a unique syndrome considered a prelude to rheumatoid arthritis (RA). It is characterized by recurrent, unpredictable episodes of joint inflammation and distinct clinical features. Unlike RA, PR episodes are brief and reversible, involving sudden-onset joint pain, swelling, and erythema. The exact etiology and diagnostic criteria of PR remain elusive, but it often shares autoantibodies with RA, leading patients to transition from PR to RA. The management of PR is multifaceted and empirical, involving various treatment modalities such as non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, and disease-modifying anti-rheumatic drugs (DMARDs). However, the relationship between obesity and PR remains underexplored. This case presents a 52-year-old woman, who presented to our hospital with recurrent and debilitating arthritis episodes since 2016. Initially affecting her wrists and later extending to her knees, shoulders, and back, these episodes severely impaired her daily activities. Despite a diagnosis of RA in 2019, supported by a positive rheumatoid factor (RF) test, and subsequent DMARD treatment, her symptoms persisted. In 2022, during her examinations at our hospital, the distinctive pattern of intermittent symptoms accompanied by damage-free joints was unveiled, suggesting a potential diagnosis of palindromic rheumatism. Notably, this case highlights the potential association between obesity and PR, as the patient's decision to undergo bariatric surgery in 2022 led to substantial weight loss of over 36 kg. This weight reduction yielded remarkable improvements in her condition, resulting in reduced frequency and severity of PR attacks. As a consequence, her medication regimen was simplified, emphasizing the therapeutic role of weight management in PR. This case paves the way for further research into the relationship between obesity, PR, and non-pharmacological interventions in PR management.

Evaluation of the NHS England 'Op COURAGE' High Intensity Service for military veterans with significant mental health problems.

INTRODUCTION: In November 2020, The NHS for England launched a pilot High Intensity Service (HIS) programme for treating military veterans complex mental health problems. Seven regional grants were awarded to manage the HIS, including NHS Solent, in South East England. This paper details an evaluation of the HIS, which was conducted from February 2021 to August 2022. METHODS: This mixed-methods study gained quantitative data from a specifically designed questionnaire that included a number of validated psychometric questionnaires. These were completed by either HIS staff or beneficiaries at entry and exit from the HIS, and qualitative data were gained from semi-structured interviews with the HIS staff. RESULTS: Data were sourced from 45 pre-questionnaires, 25 post programme questionnaires and 11 interviews. This evaluation identified reductions in situational stressors, symptoms and reported illnesses for veterans in crisis. There were reductions in depression, anxiety and post-traumatic stress disorder following programme exit. Staff reported that there was no notable changes in stress levels which appeared to remain high at programme exit. Staff interviews highlighted the importance of simultaneously understanding the social and psychological needs of veterans in mental health crisis. The benefits of integrating veteran staff members into military veteran health services were identified, demonstrating improvements in education around military culture in civilian services. CONCLUSIONS: The importance of collaboration between clinical and veteran staff members in veteran health services was noted, demonstrating the positive impact social care provision has on veteran's overall health and well-being. Veteran engagement with the service was advocated as a result of veterans accessing the service feeling understood. This first independent evaluation of the HIS provides a positive reflection, and adds to the limited empirical evidence exploring veteran engagement in health services.

Collection techniques of touch DNA deposited on human skin following a strangulation scenario.

Trace DNA is a significant type of evidence for its ability to be collected from touched items or surfaces at crime scenes to link suspects to their crimes. In cases of violent crimes like assault, sexual offences, or even homicide, often touch DNA is collected from the victim's skin. However, the collection of touch DNA from the victim's skin can be complex because of the mixture of DNA present, as there is likely to be a small quantity of the offender's DNA compared to the victim's DNA. Validating different collection methods or techniques can improve touch DNA sampling; therefore, this study investigated three collection techniques involving cotton and nylon swabs to test their efficiency for the collection of touch DNA from the human neck. There was a significant difference between the three recovery techniques used to recover touch DNA with a cotton swab (CS) (p < 0.05) and nylon swab (NS) (p < 0.05), with more alleles observed when the neck skin was moistened with 100 µL of distilled water using a spray bottle before collection with both swabs.

New novel thermal insulation and sound-absorbing materials from discarded facemasks of COVID-19 pandemic.

Due to the COVID-19 pandemic, people were encouraged and sometimes required to wear disposable facemasks, which then are discarded creating an environmental problem. In this study, we aim at investigating novel ideas to recycle wasted facemasks in order to lower the environmental impact. An experimental study has been carried out to investigate the possibility of using discarded masks for thermal insulation and sound absorption. The wasted masks are simulated by new masks, which stripped off the nose clips, elastic ear loops and are heated to 120 °C for one hour to kill any biological contaminants. The masks are also melted to investigate their thermal insulation and sound absorption properties. Results show that the thermal conductivity coefficients of the loose and melted masks are 0.03555 and 0.08683 W/m K, respectively, at room temperature of about 25 °C. Results show also that the sound absorption coefficient for loose masks is above 0.6 for the frequency range 600-5000 Hz. The loose facemasks are found to be thermally stable up to 295 °C, elastic ear loops at 304.7 °C, and the composite (melted) facemasks at 330.0 °C using the thermo-gravimetric analysis. Characterization of the facemask's three-layer fibers and the composite (melted) samples is obtained using scanning electron microscopy (SEM). The three-point bending test is obtained for the composite specimens showing good values of flexural stress, flexural strain, and flexural elastic modulus. These results are promising about using such discarded masks as new thermal insulation and sound-absorbing materials for buildings replacing the synthetic or petrochemical insulation materials.

Malpractice litigation and spinal surgery in the National Health Service: a single tertiary-level centre perspective over 12 years.

INTRODUCTION: Medical malpractice litigation is a major concern for all spine surgeons. Our aim was to evaluate the incidence and burden of successful litigation relating to the management of spinal disorders over 12 years within a UK NHS tertiary-level spinal unit and compare these litigation costs with those of other specialties. METHODS: We obtained all data held by our claims department from its inception in January 2008 to December 2019. We also obtained costs for the total financial burden incurred by our Trust during this period. RESULTS: In total, there were 83 closed claims involving spinal pathologies. Over 80% of these comprised negligent surgery (n = 28, 34%), delay to diagnose/treat (n = 25, 30%) and negligent care (n = 18, 22%). The vast majority of claims were withdrawn without incurring any cost to the hospital (n = 59, 71%) and only 24 (29%) resulted in successful litigation for the claimant. The total cost of damages for these 24 successful claims was just over £8 million, including legal costs of £2.5 million, out of total litigation costs of £381 million over this period. DISCUSSION: Fewer than 30% of initial claims against a tertiary spinal surgical referral unit resulted in a successful financial outcome for the claimant. The total costs incurred were just over £8 million, with one-third apportioned to high legal costs, reflecting the complexity of resolving spinal litigation. Our entire legal expenses accounted for only 2% of the total legal bill paid by our hospital over a 12-year period.

Preparation of a Sustainable Shape-Stabilized Phase Change Material for Thermal Energy Storage Based on Mg2+-Doped CaCO3/PEG Composites.

The properties of polyethylene glycol-6000 (PEG)/MgCaCO3, a low-cost shape-selective phase change material (ss-PCM), make it highly suitable for solar thermal applications. Nanosized porous MgO-doped CaCO3 with Mg molar concentrations of 5%, 10%, and 15% were synthesized using a hydrothermal technique. The prepared MgO-CaCO3 matrices were then impregnated with PEG to obtain PEG/MgCaCO3 as an ss-PCM. Samples identified as PEG-5MgCaCO3 (P-5-MCC), PEG-10MgCaCO3 (P-10-MCC), and PEG-15MgCaCO3 (P-15-MCC) were prepared and studied. Interestingly, P-10-MCC has the smallest particle size together with a good porous structure compared to the other two materials. The results of thermogravimetric analyses and differential scanning calorimetry indicate that the small particle size and porous structure facilitate the impregnation of approximately 69% of the PEG into the 10-MCC matrix. The latent heat and energy storage efficiency of PEG in the P-10-MCC sample are 152.5 J/g and 96.48%, respectively, which are significantly higher than those of comparable materials. Furthermore, in addition to the improvement of the thermal conductivity of the P-10-MCC, its supercooling is also reduced to some extent. The combined mesoporous and macro-porous structure of P-10-MCC is critical to retaining a large amount of PEG within the matrix, resulting in a high latent heat in the operating temperature range of 35-57 °C. The P-10MCC sample also demonstrates a high energy storage capacity (98.59%), high thermal energy storage/release rates, and exceptional shape-stabilized PCM properties.

The role of artery-preserving varicocelectomy in subfertile men with severe oligozoospermia: a randomized controlled study.

BACKGROUND: There is wide agreement nowadays that a clinical varicocoele should be ligated to treat male factor infertility. However, the significance of testicular artery preservation in patients with severe oligozoospermia has not been addressed before. OBJECTIVES: To assess the outcome of varicocelectomy in infertile men with severe oligozoospermia and clinical varicocoeles and to compare internal spermatic artery preservation vs. artery ligation. MATERIALS AND METHODS: This prospective randomized study included 302 infertile patients with severe oligozoospermia and clinical (grade II/III) varicocoeles. Patients were randomized into two groups: group A (150 patients) underwent artery-preserving varicocelectomy (APV) and group B (152 patients) underwent artery-ligating varicocelectomy (ALV). The primary outcome was to assess the changes in sperm density and motility at 3 and 6 months postoperatively in both groups. The secondary outcome was to compare the natural pregnancy rate at 1-year of follow-up. Univariate and multivariate analyses were performed to determine factors affecting pregnancy rate. RESULTS: In both groups, there was a statistically significant improvement in sperm density and motility at 3 and 6 months postoperatively. In group A, there was a greater improvement in sperm density (p < 0.001) and motility (p < 0.001) compared to group B. At 1-year follow-up, overall 35.1% achieved a natural pregnancy. Group A achieved a significantly higher natural pregnancy rate (40% vs. 30%, p value = 0.03) compared to group B. Smaller testicular volume and ALV were the independent predictors of lower pregnancy rate ((HR = 3.2, 95% CI 1.2-8.3, p = 0.01) and (HR = 3.2, 95% CI 1.4-7.1, p = 0.003), respectively). CONCLUSION: In men with severe oligozoospermia and a clinical varicocoele, APV results in improved outcomes as compared to ALV with respect to semen parameters and natural pregnancy rates. Therefore, all attempts should be made to preserve internal spermatic arteries (ISA) during varicocelectomy in men with severe oligozoospermia.

Thermal Sensitivity of Gypsy Moth (Lepidoptera: Erebidae) During Larval and Pupal Development.

As global temperatures rise, thermal limits play an increasingly important role in determining the persistence and spread of invasive species. Gypsy moth (Lymantria dispar L. Lepidoptera: Erebidae) in North America provides an ideal system for studying the effect of high temperatures on invasive species performance. Here, we used fluctuating temperature regimes and exposed gypsy moth at specific points in development (first-fourth instar, pupa) to cycles of favorable (22-28°C) or high-temperature treatments (30-36°C, 32-38°C, 34-40°C) for either 2 or 7 d. We measured survival, growth, and prolonged effects of exposure on development time and pupal mass. Survival generally decreased as the experimental temperature treatment and duration of exposure increased for all instars and pupae, with a narrow threshold for lethal effects. In response to increasing temperature and magnified by longer exposure times, growth abruptly declined for third instars and development time increased for pupae. For those surviving the 2-d exposure treatment, development time to pupation increased for all instars, but we did not find consistent effects on final pupal mass. These negative effects of high temperature provide important data on the susceptibility of gypsy moth to heat at different points in development. This work improves our understanding of thermal limits to growth and development in gypsy moth and can aid in determining invasion potential under current and future climates.

Whole-exome sequencing of cell-free DNA and circulating tumor cells in multiple myeloma.

Liquid biopsies including circulating tumor cells (CTCs) and cell-free DNA (cfDNA) have enabled minimally invasive characterization of many cancers, but are rarely analyzed together. Understanding the detectability and genomic concordance of CTCs and cfDNA may inform their use in guiding cancer precision medicine. Here, we report the detectability of cfDNA and CTCs in blood samples from 107 and 56 patients with multiple myeloma (MM), respectively. Using ultra-low pass whole-genome sequencing, we find both tumor fractions correlate with disease progression. Applying whole-exome sequencing (WES) to cfDNA, CTCs, and matched tumor biopsies, we find concordance in clonal somatic mutations (~99%) and copy number alterations (~81%) between liquid and tumor biopsies. Importantly, analyzing CTCs and cfDNA together enables cross-validation of mutations, uncovers mutations exclusive to either CTCs or cfDNA, and allows blood-based tumor profiling in a greater fraction of patients. Our study demonstrates the utility of analyzing both CTCs and cfDNA in MM.

Effects of pioglitazone on ventricular myocyte shortening and Ca(2+) transport in the Goto-Kakizaki type 2 diabetic rat.

Pioglitazone (PIO) is a thiazolidindione antidiabetic agent which improves insulin sensitivity and reduces blood glucose in experimental animals and treated patients. At the cellular level the actions of PIO in diabetic heart are poorly understood. A previous study has demonstrated shortened action potential duration and inhibition of a variety of transmembrane currents including L-type Ca(2+) current in normal canine ventricular myocytes. The effects of PIO on shortening and calcium transport in ventricular myocytes from the Goto-Kakizaki (GK) type 2 diabetic rat have been investigated. 10 min exposure to PIO (0.1-10 microM) reduced the amplitude of shortening to similar extents in ventricular myocytes from GK and control rats. 1 microM PIO reduced the amplitude of the Ca(2+) transients to similar extents in ventricular myocytes from GK and control rats. Caffeine-induced Ca(2+) release from the sarcoplasmic reticulum and recovery of Ca(2+) transients following application of caffeine and myofilament sensitivity to Ca(2+) were not significantly altered in ventricular myocytes from GK and control rats. Amplitude of L-type Ca(2+) current was not significantly decreased in myocytes from GK compared to control rats and by PIO treatment. The negative inotropic effects of PIO may be attributed to a reduction in the amplitude of the Ca(2+) transient however, the mechanisms remain to be resolved.

Titania modified activated carbon prepared from sugarcane bagasse: adsorption and photocatalytic degradation of methylene blue under visible light irradiation.

Activated carbon (AC), prepared from sugarcane bagasse waste through a low-temperature chemical carbonization treatment, was used as a support for nano-TiO2. TiO2 supported on AC (xTiO2-AC) catalysts (x = 10, 20, 50, and 70 wt.%) were prepared through a mechano-mixing method. The photocatalysts were characterized by Raman, X-ray diffraction analysis, FTIR, SBET, field emission scanning electron microscope, and optical technique. The adsorption and photo-activity of the prepared catalysts (xTiO2-AC) were evaluated using methylene blue (MB) dye. The photocatalytic degradation of MB was evaluated under UVC irradiation and visible light. The degradation percentage of the 100 ppm MB at neutral pH using 20TiO2-AC reaches 96 and 91 after 180 min under visible light and UV irradiation, respectively. In other words, these catalysts are more active under visible light than under UV light irradiation, opening the possibility of using solar light for this application.

[Chronic pain in general practice : Results from pain specialists]. / Chronischer Schmerz in der Praxis : Daten aus dem niedergelassenen Bereich.

BACKGROUND: There is currently a lack of data on chronic pain in general practice. METHODS: Over a period of 2 years, data from 12,271 patients visiting a pain specialist on an outpatient basis were collected. All patients had documented their pain history (German pain questionnaire) via tablet/computer into a databank. RESULTS: Data from 12,246 patients from 30 pain clinics could be evaluated. The proportion of women was higher (67%). The majority of patients suffered from back pain (52%). The majority of patients were treated with injections (73%), and the majority of physicians were orthopedic surgeons (71%). A minority of patients had received psychological treatment (< 30%). CONCLUSION: Comprehensive pain documentation by the patients themselves is possible by means of a computer-based program. Back pain is the main problem in patients visiting a pain specialist. Invasive methods are the mainstay of treatment approaches. The psychosocial background of chronic pain seems to be underestimated in the treatment.

The LIN28B/let-7 axis is a novel therapeutic pathway in multiple myeloma.

MYC is a major oncogenic driver of multiple myeloma (MM) and yet almost no therapeutic agents exist that target MYC in MM. Here we report that the let-7 biogenesis inhibitor LIN28B correlates with MYC expression in MM and is associated with adverse outcome. We also demonstrate that the LIN28B/let-7 axis modulates the expression of MYC, itself a let-7 target. Further, perturbation of the axis regulates the proliferation of MM cells in vivo in a xenograft tumor model. RNA-sequencing and gene set enrichment analyses of CRISPR-engineered cells further suggest that the LIN28/let-7 axis regulates MYC and cell cycle pathways in MM. We provide proof of principle for therapeutic regulation of MYC through let-7 with an LNA-GapmeR (locked nucleic acid-GapmeR) containing a let-7b mimic in vivo, demonstrating that high levels of let-7 expression repress tumor growth by regulating MYC expression. These findings reveal a novel mechanism of therapeutic targeting of MYC through the LIN28B/let-7 axis in MM that may impact other MYC-dependent cancers as well.