Intrapatient variation in PD-L1 expression and tumor mutational burden and the impact on outcomes to immune checkpoint inhibitor therapy in patients with non-small-cell lung cancer.

BACKGROUND: Programmed death receptor ligand 1 (PD-L1) tumor proportion score (TPS) and tumor mutational burden (TMB) are key predictive biomarkers for immune checkpoint inhibitor (ICI) efficacy in non-small-cell lung cancer (NSCLC). Data on their variation across multiple samples are limited. PATIENTS AND METHODS: Patients with NSCLC and multiple PD-L1 TPS and/or TMB assessments were included. Clinicopathologic and genomic data were analyzed according to PD-L1 and TMB variation. RESULTS: In total, 402 PD-L1 sample pairs and 413 TMB sample pairs were included. Concordance between pairs was moderate for PD-L1 (ρ = 0.53, P < 0.0001) and high for TMB (ρ = 0.80, P < 0.0001). Shorter time between biopsies correlated with higher concordance in PD-L1, but not in TMB. Major increases (ΔTPS ≥ +50%) and decreases (ΔTPS ≤ -50%) in PD-L1 were observed in 9.7% and 8.0% of cases, respectively. PD-L1, but not TMB, decreased with intervening ICI (P = 0.02). Acquired copy number loss of CD274, PDCD1LG2, and JAK2 were associated with major decrease in PD-L1 (q < 0.05). Among patients with multiple PD-L1 assessments before ICI, cases where all samples had a PD-L1 ≥1%, compared to cases with at least one sample with PD-L1 <1% and another with PD-L1 ≥1%, achieved improved objective response rate and progression-free survival (PFS). Among patients with at least one PD-L1 <1% and one ≥1% before ICI, cases where the most proximal sample was PD-L1 ≥1% had longer median PFS compared to cases where the most proximal PD-L1 was <1%. Among patients with multiple TMB assessments before ICI, patients with a TMB ≥10 mut/Mb based on the most recent assessment, as compared to those with a TMB <10 mut/Mb, achieved improved PFS and overall survival to ICI; instead, no differences were observed when patients were categorized using the oldest TMB assessment. CONCLUSIONS: Despite intrapatient concordance in PD-L1 and TMB, variation in these biomarkers can influence ICI outcomes, warranting consideration for reassessment before ICI initiation when feasible.

Unusual Presentation of Pleural Space Ascariasis Infection from Eastern Sudan: A Case Report.

Background: Ascaris lumbricoides is a common infectious parasite of the gastrointestinal tract worldwide, but the invasion of the pleural cavity is rare. Case Report: A 45-year-old man from Eastern Sudan presented to the emergency department complaining of breathlessness, cough stained with blood, and chest pain one month before his presentation. Also, he complained of high-grade fever for two weeks associated with sweating. Diagnosis of hydropneumothorax was made and a chest tube was inserted, two days later we found three adult A. lumbricoides worms in the chest drain. Conclusion: The patient was treated with Albendazole 200 mg, orally twice, daily for seven days, he improved and was referred to a cardiothoracic surgeon for more assessment. Our study highlights that internal medicine specialists should know about pleural ascariasis when patients present with respiratory signs and symptoms, especially in A. lumbricoides endemic regions like Eastern Sudan.

The association between a rotator cuff tendon tear and a tear of the long head of the biceps tendon: Chart review study.

Rotator cuff (RC) and long head of the biceps tendon (LHBT) tears are common shoulder problems presented to the orthopedic clinic. The aim of this study was to assess the association between RC and LHBT tears among a Saudi population sample. A total of 243 patients who were diagnosed with shoulder pain due to RC or LHBT tear between 2016 and 2018 using a magnetic resonance imaging scan were included in this study. Females comprised 66% of the sample, and 59% (n = 143) of the shoulders were on the right side. The mean age of the patients was 58 ± 11 years, ranging from 23 to 88 years. A significant association was detected between the LHBT and RC tears (P < 0.001). Out of 26 cases showing RC and LHBT tears, 81% had a full thickness tear, whereas 19% had a partial tear. The LHBT tears were presented significantly in 48% of cases with at least two completely torn RC compared to 10% in cases with one completely torn RC (P < 0.001). The LHBT tear was significantly observed in shoulders with RC tears including the tendons of subscapularis, supraspinatus, and infraspinatus, but not the teres minor (P < 0.001). Both types of tears were presented significantly in senior patients aged more than 65 years compared to younger patients (P < 0.01). Thus, the LHBT should be assessed carefully in shoulders with more than one RC tear or in chronic cases.

Predicting immunogenicity of COVID-19 vaccines in hemodialysis patients with renal disease.

Individuals who are diagnosed with chronic kidney disease, particularly those receiving maintenance hemodialysis treatment, face a greater likelihood of suffering from severe symptoms and fatality due to COVID-19. This study aimed to explore the optimal vaccination approach for these individuals. The study used data analysis tasks such as data preprocessing, cleaning, and exploration, and machine learning models including linear regression, random forest, XGBoost, gradient boosting, AdaBoost, decision trees, Lasso, and ridge regression were used to construct the predictive model. The study found that the Lasso model performed the best overall in predicting anti-S IgG antibodies levels in response to COVID-19 vaccines for people with kidney failure with MAE of 8.81, RMSE of 19.59, and R2 value of 0.93. The adjusted R2 value for the Lasso model was also 0.93, indicating that the model's ability to explain the variance in the data was not affected by the number of predictors in the model. The Random Forest model best predicted the duration of immunogenicity, with R2 and adjusted R2 values of 0.71 and 0.69, respectively. The ensemble model that includes all eight models, i.e., Ridge, Lasso, Linear Regression, Random Forest, AdaBoost, Gradient Boosting, XGBoost, and Decision Tree, has the best performance with the lowest MAE, the lowest RMSE, the highest R2, and the highest adjusted R2 values of 3.91, 5.00, 0.73, and 0.72, respectively. However, further research is required to validate these models and extend their application to different populations and vaccine types, as well as considering other factors that may affect immune response to COVID-19 vaccines. These findings can be helpful in improving vaccination strategies and promoting public health.

Tumor mutational burden for the prediction of PD-(L)1 blockade efficacy in cancer: challenges and opportunities.

Tumor mutational burden (TMB) is a biomarker that measures the number of somatic mutations in a tumor's genome. TMB has emerged as a predictor of response to immune checkpoint inhibitors (ICIs) in various cancer types, and several studies have shown that patients with high TMB have better outcomes when treated with programmed death-ligand 1-based therapies. Recently, the Food and Drug Administration has approved TMB as a companion diagnostic for the use of pembrolizumab in solid tumors. However, despite its potential, the use of TMB as a biomarker for immunotherapy efficacy is limited by several factors. Here we review the limitations of TMB in predicting immunotherapy outcomes in patients with cancer and discuss potential strategies to optimize its use in the clinic.

Knowledge of Sickle Cell Disease Among Medical Students at Al-Baha University, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Sickle cell disease (SCD) presents a major health challenge in Saudi Arabia due to its high prevalence. The important role of medical students as future healthcare leaders necessitates high awareness and knowledge about the disease. AIM: To assess SCD awareness among Al-Baha University medical students, and to evaluate its relation to gender and academic level. METHODS: A cross-sectional study was conducted, including 105 medical students from the first to sixth year at Al-Baha University. Data collection utilized an online self-administered questionnaire, covering demographic characteristics and assessing SCD knowledge. Fisher's exact and Pearson Chi-squared tests were employed to analyze associations between gender, academic level, and SCD awareness. RESULTS: The majority of male participants 52 (89.6%) and all females 47 (100%) demonstrated awareness of SCD. Clinical year enrollment (68.6%) correlated with heightened awareness across various aspects of SCD compared to the preclinical year. Most participants were in clinical years (68.6%), and 94.3% of them had knowledge about SCD. Approximately, 75 (71%) of participants correctly identified features of sickle cell crisis, 83 (79%) reported the accurate cause of SCD, and 75 (71%) cited the appropriate preventive measures. Only 15 (14%) demonstrated knowledge of correct management of SCD. Contrarily, 84 (80%) were aware of SCD complications, 66 (63%) recognized different SCD types, 67 (64%) felt adequately informed about SCD, and 34 (32%) were involved in SCD counseling. Male participants exhibited greater awareness of SCD features than females. Notably, involvement in SCD counseling was more prevalent among students of clinical years. CONCLUSION: This study underscores the need for targeted educational initiatives, particularly among preclinical year students to enhance SCD awareness among students. We also emphasize the role of clinical education in fostering a comprehensive understanding of SCD, with increased participation in counseling programs.

Rapid screening of bacteriostatic and bactericidal antimicrobial agents against Escherichia coli by combining machine learning (artificial intelligence) and UV-VIS spectroscopy.

Antibiotics are compounds that have a particular mode of action upon the microorganism they are targeting. However, discovering and developing new antibiotics is a challenging and timely process. Antibiotic development process can take up to 10-15 years and over $1billion to develop a single new therapeutic product. Rapid screening tools to understand the mode of action of the new antimicrobial agent are considered one of the main bottle necks in the antimicrobial agent development process. Classical approaches require multifarious microbiological methods and they do not capture important biochemical and organism therapeutic-interaction mechanisms. This work aims to provide a rapid antibiotic-antimicrobial biochemical diagnostic tool to reduce the timeframes of therapeutic development, while also generating new biochemical insight into an antimicrobial-therapeutic screening assay in a complex matrix. The work evaluates the effect of antimicrobial action through "traditional" microbiological analysis techniques with a high-throughput rapid analysis method using UV-VIS spectroscopy and chemometrics. Bacteriostatic activity from tetracycline and bactericidal activity from amoxicillin were evaluated on a system using non-resistant Escherichia coli O157:H7 by confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and UV-VIS spectroscopy (high-throughput analysis). The data were analysed using principal component analysis (PCA) and support vector machine (SVM) classification. The rapid diagnostic technique could easily identify differences between bacteriostatic and bactericidal mechanisms and was considerably quicker than the "traditional" methods tested.

New Insight into the Possible Roles of L-Carnitine in a Rat Model of Multiple Sclerosis.

OBJECTIVE: We investigated the effect of L-carnitine (LC) on cuprizone (Cup) demyelinating rat model and its possible underlying mechanisms. METHODS: Thirty male Sprague-Dawley (SD) rats were randomly allocated to three groups: the normal control group; the Cup group, in which Cup was administrated at a dose of 450 mg/kg per day orally via gastric gavage for 5 weeks; and the Cup + LC group, which received the same dose of Cup as the Cup group, except that the rats were treated additionally with LC 100 mg/kg/day orally for 5 weeks. The nerve conduction (NCV) in isolated sciatic nerves was measured; then, the sciatic nerves were isolated for H&E staining and electron microscope examination. The expression of myelin basic protein (MBP), IL-1ß, p53, iNOS, and NF-KB by immunohistochemistry was detected in the isolated nerves. A PCR assay was also performed to detect the expression of antioxidant genes Nrf2 and HO-1. In addition, the level of IL-17 was measured by ELISA. RESULTS: There was a significant reduction in NCV in the Cup group compared to normal rats (p < 0.001), which was significantly improved in the LC group (p < 0.001). EM and histopathological examination revealed significant demyelination and deterioration of the sciatic nerve fibers, with significant improvement in the LC group. The level of IL-17 as well as the expression of IL-1ß, p53, iNOS, and NF-KB were significantly increased, with significant reduction expression of MBP in the sciatic nerves (p < 0.01), and LC treatment significantly improved the studied parameters (p < 0.01). CONCLUSION: The current study demonstrates a neuroprotective effect of LC in a Cup-induced demyelinating rat model. This effect might be due to its anti-inflammatory and antioxidant actions.

Attitudes of dental patients towards participation in research

The attitudes of dental patients towards participation in research and the independent socioeconomic factors associated with these attitudes are not known.A self-administered questionnaire was distributed to 120 patients attending dental clinics in Amman, Jordan.For patients who had previously participated in research [N = 28], motivating factors for most [>75%]included a desire to help others and to advance science.Most respondents [81.7%]showed interest in participating in questionnaire-based research, but fewer would participate in invasive research, e.g.biopsies [22.0%]and drilling teeth [21.2%]. Reasons given for not participating in research included fear of infectious diseases [71.3%]and pain [62.1%]. Factors considered important in enhancing research participation included being asked to give informed consent [98.2%], fairness in selection of participants [97.3%]and the prospect of humanitarian benefit [96.5%]. Sex and education level were significantly associated with patients' perceptions for several of items.To enhance recruitment, researchers should be aware of people's perspectives regarding participation in research

من غير المعروف ما هي مواقف مرضى طب الأسنان تجاه المساهمة في البحوث، وما هي العوامل الاقتصادية والاجتماعية المستقلة التي ترافق هذه المواقف. وقد وزع الباحثون استبيانا يدار ذاتيا على 120 مريضا يزورون عيادات طب الأسنان في عمن، الأردن، واتضح أن العوامل المحفزة الأكثر شيوعا [أكثر من 75 %]لدى المرضى الذين ساهموا من قبل في البحوث هي رغبتهم في مساعدة الآخرين والتطور العلمي، وقد أبدى معظم المستجيبين [81.7 %]الرغبة في المشاركة في البحوث المرتكزة على الاستبيانات، إلا أن عددا أقل من ذلك كان يرحب بالمشاركة في البحوث الباضعة، مثل الخزعات 22 % وحفر الأسنان 21.2 %. وكانت أسباب عدم المشاركة في البحوث تتضمن الخوف من الأمراض المعدية [71.3 %]، والألم [62.1%]ومن العوامل التي تعتبر هامة في تعزيز المساهمة في البحوث أن يطلب من المشاركين موافقة مستنيرة [98.2 %]، والإنصاف في اختيار المشاركين [97.3%]، والتطلع إلى فائدة الإنسانية [96.5 %]. وقد كان هناك ارتباط يعتد به إحصائيا بين الجنس والمستوى التعليمي وبين إدراك المرضى لعدد من بنود الاستبيان، وخلص الباحثون إلى أن عليهم أن يدركوا تطلعات الناس حول المساهمة في البحوث، من أجل تعزيز إسهامهم فيها

Les attitudes des patients dentaires vis-à-vis de la participation à la recherche et les facteurs socioéconomiques indépendants associés à ces attitudes ne sont pas connues.Un auto-questionnaire a été distribué à 120 patients consultant dans des centres de soins dentaires à Amman [Jordanie]. Parmi les facteurs de motivation pour la majorité [>75 %]des patients ayant déjà participé à une étude de recherche [n = 28], on peut citer le désir d'aider autrui et de faire avancer la science.La plupart des répondants [81, 7 %]exprimaient un intérêt pour la participation à une recherche menée à partir d'un questionnaire, mais ils étaient moins nombreux à être volontaires pour participer à une recherche invasive, telles que des biopsies [22, 0 %]et le forage de dents [21, 2 %]. La peur des maladies infectieuses [71, 3 %]et la douleur [62, 1 %]étaient les raisons citées pour ne pas participer à une recherche.Les facteurs considérés comme importants pour améliorer la participation à la recherche comprenaient l'obtention d'un consentement éclairé [98, 2 %], l'équité dans la sélection des participants [97, 3 %]et la perspective d'un avantage humanitaire [96, 5 %]. Le sexe et le niveau d'études étaient fortement associés à la perception des patients pour plusieurs items.Afin d'intensifier le recrutement, les chercheurs devraient être informés des points de vue des patients au sujet de la participation à la recherché

Seroprevalence of hepatitis A virus antibodies among a sample of Egyptian children

We determined the seroprevalence of hepatitis A virus antibodies [HAV Ab] among 296 Egyptian children aged 2.5-18 years of different social classes to ascertain whether to give HAV vaccine early in life or to leave children to acquire natural immunity. Overall 61.4% were seropositive for HAV Ab. There was a significant increase in the seroprevalence of HAV Ab with higher age and lower social class; in children aged < 6 years, 72.7% of high and 19.0% of low social class were seronegative for HAV Ab. A national vaccination programme for HAV is not a priority. We recommend vaccination against hepatitis A for high social class children at the preschool period without testing for HAV. Vaccination for middle social class children can be done, but only after testing for HAV

Disturbios de conducao do ramo direito por fechamento da comunicacao interventricular atraves de atriotomia. / Conduction disorders of right bundle by closing of the intraventricular comunication by atriotomy

Os autores avaliam os disturbios de conducao em 3 pacientes submetidos a correcao cirurgica da comunicacao interventricular (CIV) por via atrial direita. Os pacientes operados de 1978 a 1979 foram analisados eletrocardiograficamente durante 15 meses.Encontraram-se cifras mais baixas de bloqueio completo do ramo direito (BCRD), bloqueio atrioventricular total (BAVT) e hemi-bloqueio anterior esquerdo (HBAE) quando comparado a resultados de outros centros que utilizaram esta ou outra via.Devido a esta vantagem alem de preservar a integridade das fibras musculares do ventriculo direito (VD) atriotomia e uma excelente via de acesso a maioria da CIVs

Resultados tardios do tratamento cirurgico da anomalia de Ebstein. Estudo de 19 pacientes submetidos a troca valvar. / Late results of surgical treatment of Ebstein's anomaly. Study of 19 patients subjected to valve replacement

Dezenove pacientes com anomalia de Ebstein foram submetidos a correcao cirurgica cirurgica no periodo de 1965 a 1978. A indicacao para a operacao foi grave insuficiencia cardiaca (classe funcional III e IV) na maioria dos casos (16 pacientes), ou sintomas como crises de anoxia, episodios neurologicos compativeis com embolia cerebral ou rapido aumento da area cardiaca (3 pacientes em classe funcional II).Nos primeiros 10 casos o aparelho valvar tricuspide foi substituido por protese tipo Starr-Edwards, associada a plicatura da porcao atrializada do ventriculo direito em dois casos e fechamento parcial ou total da comunicacao interatrial. Nos nove pacientes subsequentes a valvula empregada foi a de dura-mater, associada a plicatura da porcao atrializada em 3 casos e fechamento parcial ou total da comunicacao interatrial. Quatro pacientes faleceram no pos-operatorio imediato, tres no primeiro grupo e um no segundo. Tres foram ao obito no pos-operatorio tardio (todos do primeiro grupo, portadores de protese tipo Starr), um 45 dias apos a operacao e dois, 11 anos apos. Dos 12 pacientes sobreviventes, 11 encontram-se em classe funcional I e um em classe funcional II