An expandable voice user interface as lab assistant based on an improved version of Google's speech recognition.

Voice assistants are potentially helpful when working in a scientific laboratory. A big challenge is the extremely specific use of language in every laboratory. As with any voice assistant, another concern is data security. Here, we present Rainbow-an open source voice user interface (VUI) for scientific laboratories, that is adaptable to any Windows PC with Internet access. We used Google Translate Site (GTS) as a voice input and output system to ensure communication to the user. The scripting language AutoIt controls GTS, executes all actions and builds the VUI. Rainbow performs tasks from three different areas-general Microsoft Windows tasks, lab-specific tasks, and device-specific tasks. We achieved significantly higher speech recognition accuracy with our VUI than with GTS alone (91.3% versus 85.1%). Because of Rainbow's architecture, it is possible to improve the voice assistant in terms of functionality and accuracy, allowing each laboratory to optimize its own Rainbow system in a user-friendly way. In a test setup, this led to a speech recognition accuracy of 98.6%. Taken together, Rainbow provides an opportunity for every scientist to implement highly specific scientific terms and tasks to this open source voice assistant system in a very user-friendly way.

Mpox in people with advanced HIV infection: a global case series.

BACKGROUND: People living with HIV have accounted for 38-50% of those affected in the 2022 multicountry mpox outbreak. Most reported cases were in people who had high CD4 cell counts and similar outcomes to those without HIV. Emerging data suggest worse clinical outcomes and higher mortality in people with more advanced HIV. We describe the clinical characteristics and outcomes of mpox in a cohort of people with HIV and low CD4 cell counts (CD4 <350 cells per mm3). METHODS: A network of clinicians from 19 countries provided data of confirmed mpox cases between May 11, 2022, and Jan 18, 2023, in people with HIV infection. Contributing centres completed deidentified structured case report sheets to include variables of interest relevant to people living with HIV and to capture more severe outcomes. We restricted this series to include only adults older than 18 years living with HIV and with a CD4 cell count of less than 350 cells per mm3 or, in settings where a CD4 count was not always routinely available, an HIV infection clinically classified as US Centers for Disease Control and Prevention stage C. We describe their clinical presentation, complications, and causes of death. Analyses were descriptive. FINDINGS: We included data of 382 cases: 367 cisgender men, four cisgender women, and ten transgender women. The median age of individuals included was 35 (IQR 30-43) years. At mpox diagnosis, 349 (91%) individuals were known to be living with HIV; 228 (65%) of 349 adherent to antiretroviral therapy (ART); 32 (8%) of 382 had a concurrent opportunistic illness. The median CD4 cell count was 211 (IQR 117-291) cells per mm3, with 85 (22%) individuals with CD4 cell counts of less than 100 cells per mm3 and 94 (25%) with 100-200 cells per mm3. Overall, 193 (51%) of 382 had undetectable viral load. Severe complications were more common in people with a CD4 cell count of less than 100 cells per mm3 than in those with more than 300 cells per mm3, including necrotising skin lesions (54% vs 7%), lung involvement (29% vs 0%) occasionally with nodules, and secondary infections and sepsis (44% vs 9%). Overall, 107 (28%) of 382 were hospitalised, of whom 27 (25%) died. All deaths occurred in people with CD4 counts of less than 200 cells per mm3. Among people with CD4 counts of less than 200 cells per mm3, more deaths occurred in those with high HIV viral load. An immune reconstitution inflammatory syndrome to mpox was suspected in 21 (25%) of 85 people initiated or re-initiated on ART, of whom 12 (57%) of 21 died. 62 (16%) of 382 received tecovirimat and seven (2%) received cidofovir or brincidofovir. Three individuals had laboratory confirmation of tecovirimat resistance. INTERPRETATION: A severe necrotising form of mpox in the context of advanced immunosuppression appears to behave like an AIDS-defining condition, with a high prevalence of fulminant dermatological and systemic manifestations and death. FUNDING: None.

Comparación Clínica de radioterapia de intensidad modulada vs. radioterapia 3D en tratamiento neoadyuvante del cáncer de recto localmente avanzado / Clinical comparison of intensity modulated radiotherapy vs. 3D radiotherapy in neoadjuvant treatment of locally advanced rectal cancer

El objetivo de este trabajo fue comparar ventajas potenciales de la radioterapia de intensidad modulada (IMRT) vs. la radioterapia 3D (3DRT) en el control loco-regional y la toxicidad aguda en pacientes con cáncer de recto localmente avanzado (CRLA). Se analizaron retrospectivamente 235 pacientes con adenocarcinoma de recto T2/T4 y N0/N1 sometidos a radioquimioterapia neoadyuvante entre febrero de 2010 y agosto de 2015. La modalidad radiante se correlacionó con los resultados clínicos (control local y a distancia) y las tasas de toxicidades agudas urinarias, hematológicas, gastrointestinales (GI) y dérmicas. Ciento cuarenta (59.6%) recibieron IMRT y 95 (40.4%) 3DRT. La mediana de seguimiento fue de 36 meses. Las tasas de recidiva local y metástasis a distancia fueron similares entre IMRT y 3DRT. No se encontraron diferencias estadísticamente significativas en control local (CL) ni en supervivencia global (SG) entre IMRT y 3DRT (p=0.56 y p=0.24, respectivamente), ni en colostomía libre para tumores rectales bajos (p=0.44). IMRT implicó menor toxicidad cutánea (p<0.001), hematológica (p<0.0001), urinaria (p=0.0017), y gastrointestinal (p=0.0006). La incidencia de diarrea grado ≥ 3 fue del 16% entre los pacientes del grupo 3DRT frente al 5% de del grupo IMRT. En el análisis univariado, el estadio clínico T, edad, KPS, y quimioterapia adyuvante se asociaron con mejor SG (todos p<0.05) y la dosis total de radiación se asoció con mejor período libre de enfermedad (p=0.0065) Postulamos que IMRT permitiría un aumento de dosis en forma segura con el potencial de aumentar la tasa de respuestas patológicas completas (RPC), en particular en tumores rectales bajos (AU)

The aim was to compare the advantages of IMRT vs. 3D in loco regional control and acute toxicity in patients with locally advanced rectum cancer. We analyzed retrospectively 235 patients with rectal adenocarcinoma T2/T4 and N0/N1 undergoing chemo radiation between February 2010 and August 2015. The radiant modality was correlated with clinical outcomes (local and systemic control) and rates of acute urinary, hematological, gastrointestinal and dermal toxicities. One hundred and forty patients (59.6%) received IMRT and 95 (40.4%) received 3D. The median follow-up time was 36 months. The rates of local recurrence and distant metastases were similar between IMRT vs. 3D. No statistically significant differences were found in local control or survival between IMRT and 3D (p=0.56 and p =0.24, respectively), nor in free colostomy for low rectal tumors (p= 0.44). IMRT resulted in lower dermal (p<0.001), hematological (p<0.0001), urinary (p=0.0017), and gastrointestinal toxicity (p=0.0006). The incidence of diarrhea grade ≥ 3 was 16% among 3D patients vs. 5% in IMRT. In the univariate analysis, clinical stage T, age, KPS, and adjuvant chemotherapy were associated with better overall survival (all p<0.05) and the total dose of radiation was associated with better disease-free period (p=0.0065). We postulate that IMRT would allow us to increase dose in a safe manner with the potential to increase rate of complete pathological responses, particularly in low rectal tumors (AU)

Cáncer anal: resultados clínicos, toxicidades y supervivencia libre de colostomía comparando técnicas de radioterapia conformada tridimensional versus radioterapia de intensidad modulada / Anal cancer: clinical results, toxicities and colostomy-free survival comparing three-dimensional conformal radiotherapy techniques versus intensity modulated radiotherapy

Las técnicas definitivas de quimio-radioterapia para el cáncer anal, radioterapia tridimensional conformada (3DCRT) o radioterapia de intensidad modulada (IMRT) dan excelentes resultados a largo plazo. Evaluamos resultados en centros de radiación basados en la comunidad. Se evaluaron retrospectivamente 281 pacientes tratados con quimio-radioterapia definitiva para carcinoma anal loco-regional, entre 2006 y 2014. El 95% realizó quimioterapia. Se evaluaron datos de toxicidades, progresión de la enfermedad y necesidad de colostomía durante el período de seguimiento. La supervivencia global, supervivencia libre de progresión y colostomía libre se calcularon con métodos de Kaplan-Meier. La edad media fue 63.7 años con seguimiento medio de 60 meses. Ciento sesenta y nueve pacientes recibieron IMRT y 112 recibieron 3DCRT. La dosis total media tumoral fue 54 Gy. El 80% experimentó complicaciones agudas, y el 56% requirió interrupción de tratamiento. No hubo diferencias significativas en supervivencia global, supervivencia libre de progresión, supervivencia libre de colostomía ni control local a dos años entre ambos grupos. La IMRT tuvo menos suspensión del tratamiento (48% vs. 65%) (p=0.0261). El grupo IMRT tuvo una reducción significativa de todas las toxicidades agudas ≥3 y gastrointestinales (GI) tardías, en comparación con los tratados con 3DCRT. Esta serie representa una de las mayores comparaciones 3DCRT vs. IMRT para el tratamiento definitivo de cáncer anal. Los resultados a largo plazo no difieren significativamente en función de la técnica de radioterapia (RT). La IMRT reduce todas las toxicidades ≥ grado 3 y la necesidad de interrupción en comparación con 3DCRT (AU)

The definitive techniques of chemo-radiotherapy for anal cancer, 3DCRT or IMRT, give excellent long-term results. We evaluated results in community-based radiation centers. We retrospectively evaluated 281 patients treated with definitive chemo-radiotherapy for locoregional anal carcinoma, between 2006 and 2014. The 95% performed chemotherapy. Toxicity data, progression of the disease, need of colostomy during the follow-up period were evaluated. Global survival (GS), progression free survival (PFS), and free colostomy survival (CFS) were calculated with Kaplan-Meier methods. Mean age was 63.7 years with a mean follow-up of 60 months. One hundred and sixty nine patients received IMRT and 112 received 3DCRT. The total mean tumor dose was 54 Gy. The 80% experienced acute complications, and 56% required treatment interruption. There was no significant difference in GS, PFS, CFS or local control at two years between both groups. The IMRT had less treatment discontinuation (48% vs. 65%) (p = 0.0261). The IMRT group had a significant reduction in all acute toxicities ≥3 and late gastrointestinal, compared with those treated with 3DCRT. This series represents one of the largest 3DCRT vs. IMRT comparisons for the definitive treatment of anal cancer. The long-term results do not differ significantly depending on the RT technique. The IMRT reduces all toxicities ≥ grade 3 and the need for interruption compared to 3DCRT (AU)

Amyloid Biomarkers in Conformational Diseases at Face Value: A Systematic Review.

Conformational diseases represent a new aspect of proteomic medicine where diagnostic and therapeutic paradigms are evolving. In this context, the early biomarkers for target cell failure (neurons, ß-cells, etc.) represent a challenge to translational medicine and play a multidimensional role as biomarkers and potential therapeutic targets. This systematic review, which follows the PICO and Prisma methods, analyses this new-fangled multidimensionality, its strengths and limitations, and presents the future possibilities it opens up. The nuclear diagnosis methods are immunoassays: ELISA, immunodot, western blot, etc., while the therapeutic approach is focused on pharmaco- and molecular chaperones.

Risk of recurrence in patients with surgically resected stage I non-small cell lung carcinoma: histopathologic and immunohistochemical analysis.

STUDY OBJECTIVE: To evaluate the prognostic value of histopathologic variables and molecular markers in a group of patients with stage I non-small cell lung cancer (NSCLC). SETTING: "María Ferrer" Hospital of Buenos Aires, Argentina. PATIENTS: Pathologic stage IA and IB patients who underwent radical surgery and nonneoadjuvant therapy for NSCLC between January 1985 and December 1999. MEASUREMENTS AND RESULTS: Fifty-three patients fulfilling the inclusion criteria were identified. The overall survival was 52.8%, and 28% of patients had recurrent disease. We found significant differences between squamous cell carcinoma (SCC) and adenocarcinoma in mitotic counting (p = 0.001) and lymphatic permeation (p = 0.01). SCCs showed higher proliferation (MIB-1 grades 2 and 3) [p = 0.001], Bcl-2 expression (p = 0.038), and CD44 expression (p = 0.019) than adenocarcinomas. The log-rank test showed that mitosis count, necrosis, MIB-1, and Bcl-2 were predictive factors for relapse. All of them were associated with increased relapse and a shorter time to recurrence. Multivariate analysis using the Cox proportional hazards regression model showed that mitosis count, Bcl-2 expression, and grade 3 of MIB-1 emerged as independent prognostic factors of recurrence. CONCLUSIONS: We found that mitosis count and MIB-1 expression had significant value to predict recurrence, reflecting the aggressiveness of high-rate proliferative tumors. We could also show that patients with positive Bcl-2 tumors had a poor outcome, probably related to the uncontrolled cell growth that the expression of Bcl-2 promotes. Our observations are of potential interest for the development of rational postresection treatment strategies based on the estimated risk of recurrence of patients with NSCLC.