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Abstract The prognosis of patients with high-risk neuroblastoma remains poor, partly due to inadequate immune recognition of the tumor. Neuroblastomas display extremely low surface MHC-I, preventing recognition by cytotoxic T lymphocytes (CTLs) and contributing to an immunosuppressive tumor microenvironment. Glycogen synthase kinase-3 beta (GSK-3β) is involved in pathways that may affect the MHC-I antigen processing and presentation pathway. We proposed that therapeutic inhibition of GSK-3β might improve the surface display of MHC-I molecules on neuroblastoma cells, and therefore tested if targeting of GSK-3β using the inhibitor 9-ING-41 (Elraglusib) improves MHC-I-mediated CTL recognition. We analyzed mRNA expression data of neuroblastoma tumor datasets and found that non-MYCN-amplified neuroblastomas express higher GSK-3β levels than MYCN-amplified tumors. In non-MYCN-amplified cells SH-SY5Y, SK-N-AS and SK-N-SH 9-ING-41 treatment enhanced MHC-I surface display and the expression levels of a subset of genes involved in MHC-I antigen processing and presentation. Further, 9-ING-41 treatment triggered increased STAT1 pathway activation, upstream of antigen presentation pathways in two of the three non-MYCN-amplified cell lines. Finally, in co-culture experiments with CD8 + T cells, 9-ING-41 improved immune recognition of the neuroblastoma cells, as evidenced by augmented T-cell activation marker levels and T-cell proliferation, which was further enhanced by PD-1 immune checkpoint inhibition. Our preclinical study provides experimental support to further explore the GSK-3β inhibitor 9-ING-41 as an immunomodulatory agent to increase tumor immune recognition in neuroblastoma.

Abstract Background Quality sleep is vital for well-being, especially for healthcare workers facing high risks of fatigue and burnout. Sleep deprivation impairs cognitive and motor functions, contributing to medical errors. Addressing sleep disorders among healthcare professionals is crucial for enhancing patient care. Tailored interventions are needed to support their well-being and improve healthcare outcomes. Objective To evaluate the effect of Sleep Quality and its Deprivation on Sudanese Healthcare Professionals amidst conflict in Sudan. Methods A cross-sectional online survey of Sudanese doctors was conducted using convenience sampling. The questionnaire covered sleep quality, daytime sleepiness, and psychological well-being. Pilot testing ensured questionnaire clarity. Data collection utilized Google Forms distributed through social media and professional networks. A minimum sample size of 384 was calculated. Statistical analysis included descriptive statistics and various tests for significance. Data were securely stored and analyzed using SPSS and R software. Results Among 649 participants, 404 (62.2%) were women, with a mean age of 30.34 years. Most were single (434, 66.9%). General practitioners constituted the largest professional group (267, 41.1%), followed by registrars/residents (142, 21.9%). Participants took an average of 43.70 minutes to fall asleep and slept an average of 5.90 hours per night. According to the PSQI, 300 (46.2%) reported mild sleep disturbance, 287 (44.2%) moderate, 42 (6.5%) severe, and only 20 (3.1%) normal sleep. The ESS revealed 285 (43.9%) with lower normal daytime sleepiness, 188 (29.0%) with higher normal, and various levels of excessive daytime sleepiness. Stress levels varied, with 398 (61.3%) reporting normal stress, while anxiety ranged from 248 (38.2%) normal to 148 (22.8%) extremely severe. Conclusion This study emphasizes the importance of addressing sleep quality, mental health, and performance challenges among Sudanese healthcare professionals. It highlights the need for hospitals to implement measures enabling more time off, adequate sleep, and reduced on-call service days. Healthcare workers must recognize the significance of these factors for their well-being and patient care quality. The research outcomes can raise awareness about the necessity of regulating healthcare practitioners' working hours and ensuring adequate sleep.

Se realizó una evaluación de las áreas susceptibles a la ocurrencia de deslizamientos en la zona costera y cuencas hidrográficas representativas del municipio Guamá. Se empleó, a través de un Sistema de Información Geográfica, el método Mora-Vahrson, con modificaciones de la propuesta original de acuerdo con las características del área. Se obtuvo el mapa de susceptibilidad, categorizado en: Baja, Moderada, Alta y Muy Alta. Como resultado de la zonificación se obtuvo que la susceptibilidad alta es la de mayor representatividad (52%); en ella se ubican localidades como El Macho, La Plata, Uvero, Montompolo y El Francés. El resultado constituye una actualización del peligro para el municipio Guamá y crea las bases para el desarrollo de estrategias locales de gestión y mitigación de los impactos.

Abstract What predicts a neighborhood’s adaptability to essential public health policies and shelter-in-place regulations that prevent the harmful spread of COVID-19? To answer this question, we present a novel application of human mobility patterns and human behavior in a network setting. We analyze 2 years of mobility data (January 2019 to December 2020) from New York City and construct weekly mobility networks between census block groups based on aggregated point-of-interest visit patterns. Our results indicate that neighborhoods’ socioeconomic and geographic characteristics play a significant role in predicting their adaptability to active shelter-in-place policies. Our simulation outcomes reveal that, alongside factors such as race, education, and income, the geographical attributes of neighborhoods, such as access to amenities that satisfy community needs are equally important factors in predicting neighborhood adaptability to public health policies. These findings offer valuable insights that can enhance urban planning strategies, thereby aiding pandemic mitigation efforts and fostering increased adaptability of urban areas in the face of exogenous shocks like the COVID-19 pandemic.

Background: A wide range of chronic diseases is associated with ROS-mediated oxidative stress. Quercetin glycoside (QG) is reported to be a powerful antioxidant with extremely high bioavailability and structural stability compared to quercetin aglycone. Hypothesis/Purpose: In this study, the antioxidant potential and cytoprotective effects of quercetin, and its glycosides isolated from Ephedra alata against oxidative damage induced by hydrogen peroxide in the cells of tetrahymena pyriformis (TEP) were evaluated and compared. Study design: Quercetin and its O-glycosides were isolated from Ephedra alata, and their chemical structures were elucidated using advanced spectroscopic techniques. The antioxidant and cytoprotective effects were evaluated using TEP cells exposed to hydrogen peroxide-induced oxidative stress. Methods: TEP cells were pretreated with quercetin aglycone (Q), isoquercetin (ISQ), or hyperin (HYP) before exposure to hydrogen peroxide (H2O2). Cell viability, lactate dehydrogenase (LDH) release, intracellular ROS levels, malondialdehyde (MDA levels, lipoperoxidation, antioxidant enzyme activity, and cleaved caspase-3 levels were measured. Results: ISQ pretreatment significantly enhanced cell survival and reduced H2O2-induced LDH release compared to Q. ISQ also decreased intracellular ROS levels, MDA levels, and lipoperoxidation, surpassing the effects of Q. Additionally, ISQ and HYP pretreatment notably increased antioxidant enzyme activity, outperforming Q. Furthermore, ISQ pretreatment significantly diminished cleaved caspase-3 levels compared to Q, indicating a potential role in preventing oxidative stress-induced apoptosis in TEP cells. Conclusion: Quercetin O-glycosides, particularly isoquercetin, from Ephedra alata exhibit superior antioxidant and cytoprotective effects compared to quercetin aglycone. These findings highlight the potential of these compounds as natural alternatives for mitigating oxidative damage and promoting cellular health. Future research should focus on elucidating the precise molecular pathways involved and evaluating their efficacy in animal models and clinical settings.

Summary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

Introducción y Objetivos: Los inventarios briológicos en los espacios protegidos cubanos apoyan la actualización de los planes de manejos al inventariar las especies, detectar sus amenazas y diseñar acciones para su conservación. El objetivo de esta investigación es caracterizar la brioflora presente en las Reservas Florísticas Manejadas La Caoba y Charrascales de Mícara, Santiago de Cuba, Cuba. M&M: En la recolecta de los especímenes se exploraron los hábitats adecuados para la instalación de los briófitos siguiendo el método del Muestro Florístico del Hábitat. En la determinación de los taxones se consultó la bibliografía especializada y las bases de datos. Todo el material colectado fue depositado en la colección Bryophyta del herbario BSC. Resultados: Se registraron para las Reservas Florísticas Manejadas La Caoba y Charrascales de Mícara 49 taxones infragenéricos de antocerotas, hepáticas y musgos. La reserva La Caoba fue la más diversa (73,5% del total) y los musgos la división mejor representada (55,1%). El sustrato epífito es el más diverso y el Bosque semideciduo mesófilo la formación vegetal mejor representada (83,3%). La totalidad de los taxones amenazados se registraron en la Reserva Florística Manejada La Caoba. Conclusiones: En las Reservas Florísticas Manejadas La Caoba y Charrascales de Mícara la brioflora se caracteriza por la presencia de taxones de amplia plasticidad ecológica y distribución geográfica. Las condiciones presentes en la reserva Charrascales de Mícara limitan el desarrollo de los briófitos. La diversidad briológica en La Caoba está amenazada por la fragmentación del hábitat debido a las alteraciones del paisaje.

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by excessive circulating toxic lipids, hepatic steatosis, and liver inflammation. Monocyte adhesion to liver sinusoidal endothelial cells (LSECs) and transendothelial migration (TEM) are crucial in the inflammatory process. Under lipotoxic stress, LSECs develop a proinflammatory phenotype known as endotheliopathy. However, mediators of endotheliopathy remain unclear. Methods: Primary mouse LSECs isolated from C57BL/6J mice fed chow or MASH-inducing diets rich in fat, fructose, and cholesterol (FFC) were subjected to multi-omics profiling. Mice with established MASH resulting from a choline-deficient high-fat diet (CDHFD) or FFC diet were also treated with two structurally distinct GSK3 inhibitors (LY2090314 and elraglusib [9-ING-41]). Results: Integrated pathway analysis of the mouse LSEC proteome and transcriptome indicated that leukocyte TEM and focal adhesion were the major pathways altered in MASH. Kinome profiling of the LSEC phosphoproteome identified glycogen synthase kinase (GSK)-3β as the major kinase hub in MASH. GSK3β-activating phosphorylation was increased in primary human LSECs treated with the toxic lipid palmitate and in human MASH. Palmitate upregulated the expression of C-X-C motif chemokine ligand 2, intracellular adhesion molecule 1, and phosphorylated focal adhesion kinase, via a GSK3-dependent mechanism. Congruently, the adhesive and transendothelial migratory capacities of primary human neutrophils and THP-1 monocytes through the LSEC monolayer under lipotoxic stress were reduced by GSK3 inhibition. Treatment with the GSK3 inhibitors LY2090314 and elraglusib ameliorated liver inflammation, injury, and fibrosis in FFC- and CDHFD-fed mice, respectively. Immunophenotyping using cytometry by mass cytometry by time of flight of intrahepatic leukocytes from CDHFD-fed mice treated with elraglusib showed reduced infiltration of proinflammatory monocyte-derived macrophages and monocyte-derived dendritic cells. Conclusion: GSK3 inhibition attenuates lipotoxicity-induced LSEC endotheliopathy and could serve as a potential therapeutic strategy for treating human MASH. Impact and Implications: LSECs under lipotoxic stress in MASH develop a proinflammatory phenotype known as endotheliopathy, with obscure mediators and functional outcomes. The current study identified GSK3 as the major driver of LSEC endotheliopathy, examined its pathogenic role in myeloid cell-associated liver inflammation, and defined the therapeutic efficacy of pharmacological GSK3 inhibitors in murine MASH. This study provides preclinical data for the future investigation of GSK3 pharmacological inhibitors in human MASH. The results of this study are important to hepatologists, vascular biologists, and investigators studying the mechanisms of inflammatory liver disease and MASH, as well as those interested in drug development.

Background: Prolapse lumbar intervertebral disc (PLID) is a localized disc displacement outside its margins is the most common source of sciatica pain, involving 1%-5% of the population annually. Standard management includes conservative management initially for a period of around 6 weeks. In general, microdiscectomy (MD) is considered a standard procedure for symptomatic cases, with approximately 60%-80% of satisfactory results. In this study, we aimed in describing experience of MD in patients diagnosed with PLID. Methods: This retrospective study has been conducted at Dr. Ziauddin University hospital, Karachi; Pakistan. The medical records from 2018 to 2020, of microdiscectomy for prolapsed intervertebral lumbar disc were studied. All patients of 18 years or more admitted with symptomatic PLID, and proceeded to single level MD have been included. The regular pre-operative work-up, surgical technique and post-operative management was followed. Data collection was performed using a standard proforma. Utilizing SPSS version 23.0, all statistical analyses were carried out a p

Background: Radius and/or ulna fractures are frequent which encounter higher emergency room visits. Despite high incidence, proper management between closed reduction and internal fixation (CRIF) with K-wires and open reduction and internal fixation (ORIF) with anatomical Volar locking plate, remains debatable. This study aimed to compare the functional outcomes between the two management protocols. Methods: A total of 118 patients with distal radius fractures were treated operatively, at Dr. Ziauddin University Hospital Karachi, from January 2017 to October 2020. Out of these, 29 patients (24.6%) were treated with CRIF and 89 patients (75.4%) with ORIF. The functional outcomes of both groups were assessed through disabilities of arm, shoulder and hand (DASH) scores at 3 and 6 months. functional outcomes were assessed through a t-test, p-value

Background: Scoliosis is defined as a three-dimensional deformity of spine. Surgical treatment is indicated for curves equal to/or more than 40 degrees in magnitude. Curve flexibility is determined preoperatively through bending films, which help in the selection of fusion levels. Surgical treatment for fully-grown spine is a spinal fusion use to inhibit the progress of deformity which further helps in balancing of both sagittal and coronal planes. Therefore, this study aimed to find out the association between predicted via bending films after correction and final surgical correction of skeletally mature patients with Adolescent Idiopathic Scoliosis (AIS). Methods: Thirty-three patients with Adolescent Idiopathic Scoliosis (AIS) were recruited for the study. Those patients were operated at Dr. Ziauddin University Hospital, Karachi from June 2016 to June 2020. Using Pre- and post-operative radiographs of the spine, Cobb values were used to calculate the percentage of correction achieved. Percentage correction (surgical) was then compared to correction possible (predicted) to find association via an independent t-test with p

Introduction: Low back pain is presented in approximately 9.4% of the world population. Acupuncture is used by Chinese traditional medicine to stimulate certain points of the body with different types of needles. Among its beneficial effects the pain remission is described. Objective: To evaluate the effectiveness of the acupuntural treatment in patients with lumbar pain assisted in the emergency room. Methods: A quasi-experiment of therapeutic intervention study (without control group) was carried out in 35 patients with lumbar pain, who were assisted in the Natural and Traditional Medicine Emergency Room of Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba, from July to December, 2021. Results: In the investigation there was a prevalence the 40-49 age group (31.4%), female sex (57.1%), housewives, serious and moderate pain at the beginning of the treatment, as well as patients without pain one hour after the therapy. As for the final clinical course, the total of the sample classified in the relieved and improved categories. Conclusions: The effectiveness of acupuncture was demonstrated in patients with acute lumbar pain.

Thermomechanical processing and alloying are two common approaches to enhance the mechanical properties of Mg. Thus, the effects of Gd and Li elements, as two elements with various properties, on the microstructure and mechanical properties of a hot-rolled and consequently annealed AZ31 alloy were analyzed. The microstructure and texture was analyzed by scanning electron microscopy and electron back scattered diffraction. Accordingly, the mean grain size of 46 μm in the AZ31 alloy was reduced to 41 and 26 μm in the AZ31–2.9Gd and AZ31–2.3Li alloys, respectively. Grain refinement occurred due to continuous dynamic recrystallization and twinning-induced recrystallization in all of the alloys. Textural evolution showed that neither Gd nor Li could inhibit the occurrence of basal texture. Room temperature mechanical properties were assessed by using the shear punch test (SPT) method. The results exhibited that the strength of the AZ31 alloy was improved from 116 MPa to 139 MPa and 141 MPa by respective additions of Gd and Li. Strength enhancement was mainly attributed to the grain boundary strengthening and second-phase particles hardening. One promising observation was the simultaneous enhancement of shear strength and ductility by the addition of Gd and Li. This observation was ascribed to the more uniform distribution of second-phase particles and lower volume fraction of twins as potential sites for crack initiation. As long as mechanical strength is concerned, results favor the use of Li as alloying element in Mg, especially due to the more noticeable lightweighting potential compared to Gd.

La producción de Ni y Co mediante la tecnología CARON en Moa, Cuba, vierte anualmente millones de toneladas de colas, que afectan al medio ambiente, con contenidos de elementos metálicos valiosos que pueden ser recuperados por diversas vías. El propósito de este trabajo es evaluar la concentración de tales elementos para diferentes clases de tamaño e intensidades del campo magnético. Para ello, se separó mediante tamizado tres clases de tamaño (gruesa +0,200 mm, media -0,200 +0,045 mm y fina -0,045 mm), a las cuales se les aplicó tres intesidades de campo magnético (0,05 A, 0,10 A y 0,15 A). Se obtuvo como resultado que en el producto no magnético para una intensidad del campo de 0,15 A, el cinc, cromo y aluminio se concentran en la clase de tamaño media y el níquel, magnesio y sílice en la clase gruesa. El hierro se concentra en el producto magnético de las clases media y gruesa para una intensidad de 0,05 A hasta aproximadamente 50 %. En la clase fina la aplicación de un campo magnético no ejerce ningún efecto. Finalmente, es posible concentrar el níquel hasta 1,23 %, en el producto no magnético de las partículas mayores de 0,045 mm, con posibilidad de incorporar este elemento valioso a la tecnología de extracción existente.

This article discusses the role of manufacturing in the economic growth of Iran using the logarithmic mean Divisia index (LMDI) method. The study identifies various drivers of industrialization and their impact on growth, including structural changes (productivity of labor and employment share in industrial factories) and employment scale. The LMDI method is used to analyze with a dataset from Iranian provinces between 1381 and 1399. The results show that industrialization has a positive and significant effect on economic growth, with structural changes having a greater impact than employment scale. The study highlights the importance of sustainable industrial development for economic growth in Iran.

Objective: To identify the etiological spectrum of obstructive jaundice in patients presenting in Bolan Medical Complex Hospital Quetta.Study type,settings& duration:This descriptive cross-sectional study was conducted at Department of General Surgery, Bolan Medical Complex Hospital, Quettafrom December 2017to June 2018.Methodology:A total number of 211 patients having age 15 to 65 years with diagnosis of obstructive jaundice were included. All radiological tests like ultrasound, CT scan and Magnetic Resonance Cholangio-pancreatography of the patients was done to determine the etiology of obstructive jaundice. After surgery,the histopathological examination of the biopsy was also done. Data analysis was done through SPSS v23 software.Results:Mean age of study patients was 47.86±12.40 years. There were 131 (62.09%) female patients and only 80 (37.91%) male patients. There were 87 (41.23%) patients who presented with benign causes while remaining 124 (58.77%) patients who presented with malignant causes. Among the benign causes, stone in common bile duct (CBD) were most common presented in 51 (24.2%) patients while 36 (17.1%) patients presented with stricture. Although pancreatic head carcinoma was the most prevalent disease diagnosed in 69 (32.7%) patients with malignant conditions, peri-ampular carcinoma in 24 (11.4%) patients, gallbladder carcinoma in 22 (10.4%), and cholangio-carcinoma in just 9 (4.3%) patients.Conclusion:As compared to benign causes, malignant causes of obstructive jaundice are more frequent. The highest prevalent tumour among malignant causes is pancreatic head carcinoma, while stones inthe common bile duct are highly prevalent among benign causes of obstruction in our population.

Abstract Background Reproduction entails substantial demands throughout its distinct stages. The mammalian gestation period imposes various energetic costs and movement deficits, but its effects on the sensory system are poorly understood. Bats rely heavily on active sensing, using echolocation to forage in complete darkness, or when lighting is uncertain. We examined the effects of pregnancy on bat echolocation. Results We show that pregnant Kuhl’s pipistrelles (Pipistrellus kuhlii) altered their echolocation and flight behavior. Specifically, pregnant bats emitted longer echolocation signals at an ~ 15% lower rate, while flying more slowly and at a lower altitude compared to post-lactating females. A sensorimotor foraging model suggests that these changes could lead to an ~ 15% reduction in hunting performance during pregnancy. Conclusions Sensory deficits related to pregnancy could impair foraging in echolocating bats. Our study demonstrates an additional cost of reproduction of possible relevance to other sensory modalities and organisms.

Sexual harassment in the workplace is an overt form of sexism that reinscribes patriarchal power relations within the university. Despite the perception that many people are reporting their harassment in academia thanks to the MeToo movement, we found the problem largely unreported in our sample of faculty and staff at US universities. Little is known about what drives reporting and disclosure behaviors of faculty and staff within institutions of higher education (IHEs). The present study was designed to examine disclosing and reporting sexual harassment in academia, using a sample of (N = 88) faculty and staff from IHEs who experienced some form of unwanted sexual attention. Approximately 40% did not report or disclose to anyone, and among those who did disclose the harassment they overwhelmingly chose people outside the workplace. The most common reasons for not reporting included not interpreting the event as serious enough, concerns of not being taken seriously, and thinking that nothing would be done. Regression analysis showed that experiencing electronic harassment, but not other forms of harassment, predicted reporting and disclosure. This finding reveals the stereotypes behind 'the perfect victim' are alive and well, continuing to limit the ability of victims to come forward with claims of harassment.

Introduction: Hypertension constitutes a problem of public health in almost all over the world. Among the risk factors associated with it, the accumulation of fat is notable, which can, in turn, establish risks and determine comorbidities and mortality associated with this nosological entity. Objective: To determine the variations in the values of the abdominal perimeter and waist-hip ratio in patients with hypertension, according to selected epidemiological and clinical variables. Methods: A descriptive, prospective and cross-sectional study was carried out on 221 patients with hypertension, belonging to doctor's office 19 of Josué País García Teaching Polyclinic in Santiago de Cuba municipality, from June, 2019 to December, 2020. Results: There was a prevalence of the female sex and the 65-74 age group (28.5%). The anthropometric indicators, abdominal perimeter and waist-hip ratio, had values that exceeded the established normal parameters for both sexes. The calculation of the abdominal perimeter revealed a predominance of obesity in the female sex, while it was classified as increased in the male sex. Conclusions: The values of the waist-hip ratio and abdominal perimeter exceeded those classified by the World Health Organization as high risk of presenting the disease in both sexes.