Detecting envelope stress by monitoring ß-barrel assembly.

The cell envelope protects bacteria from their surroundings. Defects in its integrity or assembly are sensed by signal transduction systems, allowing cells to rapidly adjust. The Rcs phosphorelay responds to outer membrane (OM)- and peptidoglycan-related stress in enterobacteria. We elucidated how the OM lipoprotein RcsF, the upstream Rcs component, senses envelope stress and activates the signaling cascade. RcsF interacts with BamA, the major component of the ß-barrel assembly machinery. In growing cells, BamA continuously funnels RcsF through the ß-barrel OmpA, displaying RcsF on the cell surface. This process spatially separates RcsF from the downstream Rcs component, which we show is the inner membrane protein IgaA. The Rcs system is activated when BamA fails to bind RcsF and funnel it to OmpA. Newly synthesized RcsF then remains periplasmic, interacting with IgaA to activate the cascade. Thus RcsF senses envelope damage by monitoring the activity of the Bam machinery.

Sequential Lateral Lymphatic Metastasis Shows Similar Oncologic Outcomes to Upward Spread in Advanced Rectal Cancer After Preoperative Chemoradiotherapy.

BACKGROUND: Whether lateral pelvic node metastasis should be considered as a regional or systemic disease is a long-standing debate. Although previous Japanese studies have considered it to be locoregional disease, Western countries consider it a systemic disease and do not perform lateral pelvic node dissection after preoperative chemoradiotherapy. OBJECTIVE: To evaluate whether lateral pelvic node metastasis is a systemic or regional disease that is amenable to curative resection. DESIGN: Retrospective analysis of a prospectively collected database. SETTING: This study was conducted at a tertiary cancer center. PATIENTS: There were 616 consecutive patients who underwent curative total mesorectal excision alone or with lateral pelvic node dissection after preoperative chemoradiotherapy for locally advanced rectal cancer between 2011 and 2019. MAIN OUTCOME MEASURES: Three-year disease-free and overall survival. RESULTS: A total of 360 patients underwent total mesorectal excision, and 160 patients underwent total mesorectal excision with lateral pelvic node dissection. There was no difference in the 3-year disease-free survival (DFS; p = 0.844) or overall survival rates ( p = 0.921) between the groups. Patients with lateral pelvic node metastasis showed DFS similar to those with perirectal lymph node metastasis in the total mesorectal excision group. In a subgroup analysis, patients with internal iliac pelvic node metastasis showed a disease-free survival comparable to those with perirectal node involvement, and patients with other lateral pelvic node metastasis showed a DFS similar to those with intermediate node involvement. In the lateral pelvic node dissection group, the lateral pelvic node metastatic rate was 32.5%. On multivariate analysis, fewer than 8 of the unilateral harvested lateral pelvic nodes and advanced ypT stage were significantly associated with poor disease-free survival. LIMITATION: The retrospective design. CONCLUSIONS: Lateral lymphatic metastasis showed oncologic outcomes similar to those of upward spread, especially perirectal lymph nodes metastasis. Large cohort studies with long-term follow-up are required to confirm these results. See Video Abstract . LAS METSTASIS LINFTICAS SECUENCIALES LATERALES MUESTRAN RESULTADOS ONCOLGICOS SIMILARES EN LA PROPAGACIN ASCENDENTE DEL CNCER RECTAL AVANZADO DESPUS DE LA RADIOQUIMIOTERAPIA PREOPERATORIA: ANTECEDENTES:Es un debate muy antiguo si las metástasis en los ganglios pélvicos laterales deben considerarse una enfermedad regional o sistémica. Si bien estudios japoneses anteriores las consideran como una enfermedad locorregional, en los países de occidente se las considera como una enfermedad sistémica por la cual no se realiza disección de ganglios pélvicos laterales después de una radioquimioterapia preoperatoria.OBJETIVOS:Evaluar si la metástasis en los ganglios pélvicos laterales se consideran como enfermedad sistémica o enfermedad regional susceptible de resección curativa.DISEÑO:Análisis retrospectivo de una base de datos recopilada prospectivamente.AJUSTE:Este estudio se realizó en un centro oncológico terciario.PACIENTES:616 pacientes consecutivos se sometieron a excisión total del mesorrecto curativa sola o con disección de los ganglios pélvicos laterales después de radioquimioterapia preoperatoria en casos de cáncer de recto localmente avanzado entre 2011 y 2019.PRINCIPALES MEDIDAS DE RESULTADO:Sobrevida global y libre de enfermedad a 3 años.RESULTADOS:Un total de 360 pacientes se sometieron a excisión total del mesorrecto y 160 pacientes se sometieron a excisión total del mesorrecto con disección de ganglios pélvicos laterales.No hubo diferencias en la sobrevida libre de enfermedad a 3 años (p = 0,844) ni en las tasas de sobrevida general (p = 0,921) entre los grupos. Los pacientes con metástasis en los ganglios pélvicos laterales mostraron una sobrevida libre de enfermedad similar a aquellos con metástasis en los ganglios linfáticos perirrectales que se encontraban en el grupo de excisión total del mesorrecto.En el análisis de subgrupos, los pacientes con metástasis en los ganglios pélvicos ilíacos internos mostraron una sobrevida libre de enfermedad comparable a aquellos con afección de los ganglios perirrectales y los pacientes con otras metástasis en los ganglios pélvicos laterales mostraron una sobrevida libre de enfermedad similar a aquellos con afección de los ganglios intermedios.En el grupo de disección de los ganglios pélvicos laterales, la tasa de metástasis en dichos ganglios fué del 32,5%. En el análisis multivariado, < de 8 ganglios pélvicos laterales resecados unilateralmente y el estadio ypT avanzado se asociaron significativamente con una menor sobrevida libre de enfermedad.LIMITACIÓN:El diseño retrospectivo del estudio.CONCLUSIONES:Las metástasis linfáticas laterales mostraron resultados oncológicos similares a la diseminación ascendente, especialmente las metástasis en los ganglios linfáticos perirrectales. Se requieren grandes estudios de cohortes con seguimiento a largo plazo para confirmar estos resultados. (Traducción-Dr. Xavier Delgadillo ).

Long-term Complications of Laparoscopic or Robotic Lateral Pelvic Node Dissection After Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer.

BACKGROUND: Patients with rectal cancer who underwent lateral pelvic node dissection might be at a higher risk of postoperative complications derived from technical complexity. However, little is known regarding the long-term complications after lateral pelvic node dissection. OBJECTIVES: The study aimed to investigate the long-term complications of preoperative chemoradiotherapy, followed by total mesorectal excision with lateral pelvic node dissection for locally advanced rectal cancers. DESIGN: A retrospective analysis of a prospectively collected database. SETTINGS: This study was conducted in a tertiary cancer center. PATIENTS: Patients with rectal cancer who underwent total mesorectal excision with lateral pelvic node dissection after preoperative chemoradiotherapy between 2011 and 2019 were analyzed. All operations were performed via a laparoscopic or robotic approach. MAIN OUTCOME MEASURES: Long-term complications were defined as adverse events that persisted or newly appeared ≥90 days after surgery and could be related to the surgery. RESULTS: A total of 164 patients underwent total mesorectal excision with lateral pelvic node dissection after preoperative chemoradiotherapy. Short-term and long-term complication rates were 36.0% and 36.6%, respectively. Lymphocele was the most common long-term complication (17.7% of patients), and 11.6% had anastomotic leakage with chronic sinus. Of the patients with long-term complications, 20.7% of patients needed readmission for treatment. Of the 29 patients with lymphocele, 13 (41.0%) experienced spontaneous absorption and 11 (37.9%) required surgical or percutaneous catheter drainage or antibiotics use. Multivariate analysis showed pathologic pelvic node metastases ( p = 0.008), and a higher number of unilateral harvested pelvic nodes ( p = 0.001) were significantly associated with long-term complications. At the last follow-up (median duration of 43 months), 15.9% of patients had unresolved complications. LIMITATIONS: The retrospective design. CONCLUSIONS: Patients undergoing lateral pelvic node dissection experienced a higher frequency of long-term complications, but half of them had asymptomatic lymphoceles, most of which resolved spontaneously. However, further efforts should be paid to reduce anticipated complications related to lateral pelvic node dissection. See Video Abstract . COMPLICACIONES A LARGO PLAZO DE LA DISECCIN DE LOS GANGLIOS LIFTICOS PLVICOS LATERALES LAPAROSCPICA O ROBTICA DESPUS DE LA QUIMIORRADIOTERAPIA PREOPERATORIA CONTRA EL CNCER DEL RECTO LOCALMENTE AVANZADO: ANTECEDENTES:Los pacientes con cáncer del recto sometidos a disección ganglionar linfática pélvica lateral podrían tener mayor riesgo de complicaciones postoperatorias derivadas de la complejidad técnica. Sin embargo, se sabe poco sobre las complicaciones a largo plazo después de la disección de los ganglios linfáticos pélvicos laterales.OBJETIVOS:Investigar las complicaciones a largo plazo de la quimiorradioterapia preoperatoria, seguida de escisión mesorrectal total con disección de los ganglios linfáticos pélvicos laterales contra el cáncer de recto localmente avanzado.DISEÑO:Un análisis retrospectivo de una base de datos recopilada prospectivamente.AJUSTES:Este estudio se llevó a cabo en un centro oncológico terciario.PACIENTES:Se analizaron pacientes con cáncer de recto que se sometieron a escisión mesorrectal total con disección de ganglios linfáticos pélvicos laterales después de quimiorradioterapia preoperatoria entre 2011 y 2019. Todas las operaciones se realizaron mediante abordaje laparoscópico o robótico.PRINCIPALES MEDIDAS DE RESULTADO:Las complicaciones a largo plazo se definieron como eventos adversos que persistieron o aparecieron recientemente ≥ 90 días después de la cirugía y podrían estar relacionados con la cirugía.RESULTADOS:Un total de 164 pacientes se sometieron a escisión mesorrectal total con disección de los ganglios linfáticos pélvicos laterales después de quimiorradioterapia preoperatoria. Las tasas de complicaciones a corto y largo plazo fueron del 36,0% y 36,6%, respectivamente. El linfocele fue la complicación a largo plazo más común (17,7% de los pacientes) y el 11,6% tuvo fuga anastomótica con seno crónico. De los pacientes con complicaciones a largo plazo, el 20,7% de los pacientes necesitaron reingreso para recibir tratamiento. De 29 pacientes con linfocele, 13 (41,0%) experimentaron absorción espontánea y 11 (37,9%) requirieron drenaje quirúrgico o percutáneo con catéter o uso de antibióticos. El análisis multivariado mostró metástasis patológicas en los ganglios linfáticos pélvicos ( p = 0,008) y un mayor número de ganglios pélvicos extraídos unilateralmente ( p = 0,001) se asociaron significativamente con complicaciones a largo plazo. En el último seguimiento (mediana de 43 meses), el 15,9% de los pacientes tuvieron complicaciones no resueltas.LIMITACIÓN:El diseño retrospectivo.CONCLUSIONES:Los pacientes sometidos a disección de ganglios pélvicos linfáticos laterales experimentaron una mayor frecuencia de complicaciones a largo plazo, pero la mitad de ellos tuvieron linfoceles asintomáticos, la mayoría de los cuales se resolvieron espontáneamente. Sin embargo, se deben realizar mayores esfuerzos para reducir las complicaciones previstas relacionadas con la disección de los ganglios linfáticos pélvicos laterales. (Traducción-Dr. Aurian Garcia Gonzalez ).

Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial).

BACKGROUND: Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). METHODS: A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. DISCUSSION: This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. TRIAL REGISTRATION: This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.

Disorder is a critical component of lipoprotein sorting in Gram-negative bacteria.

Gram-negative bacteria express structurally diverse lipoproteins in their cell envelope. Here, we find that approximately half of lipoproteins destined to the Escherichia coli outer membrane display an intrinsically disordered linker at their N terminus. Intrinsically disordered regions are common in proteins, but establishing their importance in vivo has remained challenging. As we sought to unravel how lipoproteins mature, we discovered that unstructured linkers are required for optimal trafficking by the Lol lipoprotein sorting system, whereby linker deletion re-routes three unrelated lipoproteins to the inner membrane. Focusing on the stress sensor RcsF, we found that replacing the linker with an artificial peptide restored normal outer-membrane targeting only when the peptide was of similar length and disordered. Overall, this study reveals the role played by intrinsic disorder in lipoprotein sorting, providing mechanistic insight into the biogenesis of these proteins and suggesting that evolution can select for intrinsic disorder that supports protein function.

A Comparison of Measured Airborne and Self-Reported Secondhand Smoke Exposure in the MADRES Pregnancy Cohort Study.

INTRODUCTION: Secondhand smoke (SHS) exposure during pregnancy is linked to adverse birth outcomes, such as low birth weight and preterm birth. While questionnaires are commonly used to assess SHS exposure, their ability to capture true exposure can vary, making it difficult for researchers to harmonize SHS measures. This study aimed to compare self-reported SHS exposure with measurements of airborne SHS in personal samples of pregnant women. METHODS: SHS was measured on 48-hour integrated personal PM2.5 Teflon filters collected from 204 pregnant women, and self-reported SHS exposure measures were obtained via questionnaires. Descriptive statistics were calculated for airborne SHS measures, and analysis of variance tests assessed group differences in airborne SHS concentrations by self-reported SHS exposure. RESULTS: Participants were 81% Hispanic, with a mean (SD) age of 28.2 (6.0) years. Geometric mean (SD) personal airborne SHS concentrations were 0.14 (9.41) µg/m3. Participants reporting lower education have significantly higher airborne SHS exposure (p=0.015). Mean airborne SHS concentrations were greater in those reporting longer duration with windows open in the home. There was no association between airborne SHS and self-reported SHS exposure; however, asking about the number of smokers nearby in the 48-hour monitoring period was most correlated with measured airborne SHS (Two+ smokers: 0.30µg/m3 vs. One: 0.12µg/m3 and Zero: 0.15µg/m3; p=0.230). CONCLUSIONS: Self-reported SHS exposure was not associated with measured airborne SHS in personal PM2.5 samples. This suggests exposure misclassification using SHS questionnaires and the need for harmonized and validated questions to characterize this exposure in health studies. IMPLICATIONS: This study adds to the growing body of evidence that measurement error is a major concern in pregnancy research, particularly in studies that rely on self-report questionnaires to measure secondhand smoke (SHS) exposure. The study introduces an alternative method of SHS exposure assessment using objective optical measurements, which can help improve the accuracy of exposure assessment. The findings emphasize the importance of using harmonized and validated SHS questionnaires in pregnancy health research to avoid biased effect estimates. This study can inform future research, practice, and policy development to reduce SHS exposure and its adverse health effects.

Robotic and laparoscopic salvage lateral pelvic node dissection for the treatment of recurrent rectal cancer.

BACKGROUND: The lateral pelvic sidewall is a major site of local recurrence after radical resection of rectal cancer. Salvage lateral pelvic node dissection (LPND) may be the only way to eliminate recurrent lateral pelvic nodes (LPNs). This study aimed to describe the technical details of robotic and laparoscopic salvage LPND and assess the short-term clinical and oncological outcomes in patients with recurrent LPNs who underwent salvage LPND by a minimally invasive approach for curative intent. METHODS: Between September 2010 and 2019, 36 patients who underwent salvage surgery for LPN recurrence were retrospectively analyzed from a prospectively maintained database. Patients' characteristics, index operation, MRI findings, and perioperative and pathological outcomes were analyzed. RESULTS: Eleven and 14 patients underwent robotic and laparoscopic salvage LPND, respectively. Eight patients (32.0%) underwent a combined salvage operation for resectable extra-pelvic sidewall metastases. There were four cases of open-conversion during the laparoscopic approach due to uncontrolled bleeding of iliac vessels. In these patients, metastatic LPNs were suspected of iliac vessel invasion and were found to be larger in size (median 15 mm; range 12-20) than that in patients who underwent successful LPND using the minimally invasive approach (median 10 mm; range 5-20). The median number of metastatic LPNs and harvested LPNs was 1 (range 0-3) and 6 (range 1-16), respectively. Six patients (24.0%) experienced postoperative complications including lymphoceles and voiding difficulties. During the follow-up (median 44.6 months; range 24.0-87.7), eight patients developed recurrences, mainly the lung and para-aortic lymph nodes, and one patient developed pelvic sidewall recurrence after laparoscopic salvage LPND. The 3-year disease-free survival and overall survival after salvage LPND were 66.4% and 79.2%, respectively. CONCLUSIONS: Robotic and laparoscopic salvage LPND for recurrent LPNs are safe and feasible with favorable short-term surgical outcomes. However, the surgical approach should be carefully chosen in patients with large-sized and invasive recurrent LPNs.

RoF-based indoor distributed antenna system that can simultaneously support 5G mmWave and 6G terahertz services.

The telecommunication society is paving the way toward ultra-high frequency regions, including the millimeter wave (mmWave) and sub-terahertz (sub-THz) bands. Such high-frequency electromagnetic waves induce a variety of physical constraints when they are used in wireless communications. Inevitably, the fiber-optic network is deeply embedded in the mobile network to resolve such challenges. In particular, the radio-over-fiber (RoF)-based distributed antenna system (DAS) can enhance the accessibility of next-generation mobile networks. The inherent benefits of RoF technology enhance the DAS network in terms of practicality and transmission performance by enabling it to support the 5G mmWave and 6G THz services simultaneously in a single optical transport link. Furthermore, the RoF allows the indoor network to be built based on the cascade architecture; thus, a service zone can be easily added on request. This study presents an RoF-based multi-service DAS network and experimentally investigates the feasibility of the proposed system.

Coherent terahertz wireless communication using dual-parallel MZM-based silicon photonic integrated circuits.

Coherent terahertz (THz) wireless communication using silicon photonics technology provides critical solutions for achieving high-capacity wireless transmission beyond 5G and 6G networks and seamless connectivity with fiber-based backbone networks. However, high-quality THz signal generation and noise-robust signal detection remain challenging owing to the presence of inter-channel crosstalk and additive noise in THz wireless environments. Here, we report coherent THz wireless communication using a silicon photonic integrated circuit that includes a dual-parallel Mach-Zehnder modulator (MZM) and advanced digital signal processing (DSP). The structure and fabrication of the dual-parallel MZM-based silicon photonic integrated circuit are systematically optimized using the figure of merit (FOM) method to improve the modulation efficiency while reducing the overall optical loss. The advanced DSP compensates for in-phase and quadrature (IQ) imbalance as well as phase noise by orthogonally decoupling the IQ components in the frequency domain after adaptive signal equalization and carrier phase estimation. The experimental results show a reduction in phase noise that induces degradation of transmission performance, successfully demonstrating error-free 1-m THz wireless transmission with bit-error rates of 10-6 or less at a data rate of 50 Gbps.

Structural insight into the formation of lipoprotein-ß-barrel complexes.

The ß-barrel assembly machinery (BAM) inserts outer membrane ß-barrel proteins (OMPs) in the outer membrane of Gram-negative bacteria. In Enterobacteriacea, BAM also mediates export of the stress sensor lipoprotein RcsF to the cell surface by assembling RcsF-OMP complexes. Here, we report the crystal structure of the key BAM component BamA in complex with RcsF. BamA adopts an inward-open conformation, with the lateral gate to the membrane closed. RcsF is lodged deep within the lumen of the BamA barrel, binding regions proposed to undergo outward and lateral opening during OMP insertion. On the basis of our structural and biochemical data, we propose a push-and-pull model for RcsF export following conformational cycling of BamA, and provide a mechanistic explanation for how RcsF uses its interaction with BamA to detect envelope stress. Our data also suggest that the flux of incoming OMP substrates is involved in the control of BAM activity.

Clinical adaptation of synthetic MRI-based whole brain volume segmentation in children at 3 T: comparison with modified SPM segmentation methods.

PURPOSE: To validate the use of synthetic magnetic resonance imaging (SyMRI) volumetry by comparing with child-optimized SPM 12 volumetry in 3 T pediatric neuroimaging. METHODS: In total, 106 children aged 4.7-18.7 years who underwent both synthetic and 3D T1-weighted imaging and had no abnormal imaging/neurologic findings were included for the SyMRI vs. SPM T1-only segmentation (SPM T1). Forty of the 106 children who underwent an additional 3D T2-weighted imaging were included for the SyMRI vs. SPM multispectral segmentation (SPM multi). SPM segmentation using an age-appropriate atlas and inverse-transforming template-space intracranial mask was compared with SyMRI segmentation. Volume differences between SyMRI and SPM T1 were plotted against age to evaluate the influence of age on volume difference. RESULTS: Measurements derived from SyMRI and two SPM methods showed excellent agreements and strong correlations except for the CSF volume (CSFV) (intraclass correlation coefficients = 0.87-0.98; r = 0.78-0.96; relative volume difference other than CSFV = 6.8-18.5% [SyMRI vs. SPM T1] and 11.3-22.7% [SyMRI vs. SPM multi]). Dice coefficients of all brain tissues (except CSF) were in the range 0.78-0.91. The Bland-Altman plot and age-related volume difference change suggested that the volume differences between the two methods were influenced by the volume of each brain tissue and subject's age (p < 0.05). CONCLUSION: SyMRI and SPM segmentation results were consistent except for CSFV, which supports routine clinical use of SyMRI-based volumetry in pediatric neuroimaging. However, caution should be taken in the interpretation of the CSF segmentation results.

Time-saving synthetic magnetic resonance imaging protocols for pediatric neuroimaging: impact of echo train length and bandwidth on image quality.

BACKGROUND: Synthetic MRI is a time-efficient imaging technique that provides both quantitative MRI and contrast-weighted images simultaneously. However, a rather long single scan time can be challenging for children. OBJECTIVE: To evaluate the clinical feasibility of time-saving synthetic MRI protocols adjusted for echo train length and receiver bandwidth in pediatric neuroimaging based on image quality assessment and quantitative data analysis. MATERIALS AND METHODS: In total, we included 33 children ages 1.6-17.4 years who underwent synthetic MRI using three sets of echo train length and receiver bandwidth combinations (echo train length [E]12-bandwidth [B in KHz]22, E16-B22 and E16-B83) at 3 T. The image quality and lesion conspicuity of synthetic contrast-weighted images were compared between the suggested protocol (E12-B22) and adjusted protocols (E16-B22 and E16-B83). We also compared tissue values (T1, T2, proton-density values) and brain volumetry. RESULTS: For the E16-B83 combination, image quality was sufficient except for 15.2% of T1-W and 3% of T2-W fluid-attenuated inversion recovery (FLAIR) images, with remarkable scan time reduction (up to 35%). The E16-B22 combination demonstrated a comparable image quality to E12-B22 (P>0.05) with a scan time reduction of up to 8%. There were no significant differences in lesion conspicuity among the three protocols (P>0.05). Tissue value measurements and brain tissue volumes obtained with the E12-B22 protocol and adjusted protocols showed excellent agreement and strong correlations except for gray matter volume and non-white matter/gray matter/cerebrospinal fluid volume in E12-B22 vs. E16-B83. CONCLUSION: The adjusted synthetic protocols produced image quality sufficient or comparable to that of the suggested protocol while maintaining lesion conspicuity with reduced scan time. The quantitative values were generally consistent with the suggested MRI-protocol-derived values, which supports the clinical application of adjusted protocols in pediatric neuroimaging.

How the assembly and protection of the bacterial cell envelope depend on cysteine residues.

The cell envelope of Gram-negative bacteria is a multilayered structure essential for bacterial viability; the peptidoglycan cell wall provides shape and osmotic protection to the cell, and the outer membrane serves as a permeability barrier against noxious compounds in the external environment. Assembling the envelope properly and maintaining its integrity are matters of life and death for bacteria. Our understanding of the mechanisms of envelope assembly and maintenance has increased tremendously over the past two decades. Here, we review the major achievements made during this time, giving central stage to the amino acid cysteine, one of the least abundant amino acid residues in proteins, whose unique chemical and physical properties often critically support biological processes. First, we review how cysteines contribute to envelope homeostasis by forming stabilizing disulfides in crucial bacterial assembly factors (LptD, BamA, and FtsN) and stress sensors (RcsF and NlpE). Second, we highlight the emerging role of enzymes that use cysteine residues to catalyze reactions that are necessary for proper envelope assembly, and we also explain how these enzymes are protected from oxidative inactivation. Finally, we suggest future areas of investigation, including a discussion of how cysteine residues could contribute to envelope homeostasis by functioning as redox switches. By highlighting the redox pathways that are active in the envelope of Escherichia coli, we provide a timely overview of the assembly of a cellular compartment that is the hallmark of Gram-negative bacteria.

Prognostic Value of Venous Invasion Detected by Elastin Stain May Surpass Lymph Node Status in Colon Cancer.

BACKGROUND: Venous invasion is a poor prognostic factor in colon cancer but is often underreported with significant variability. OBJECTIVES: We aimed to determine the impact of an elastin stain on venous invasion detection in colon cancer and evaluate the value of venous invasion in predicting disease recurrence in combination with lymph node status and other prognostic factors. DESIGN: This is a retrospective analysis of a prospectively collected database. SETTING: This study was conducted at a tertiary cancer center. PATIENTS: A total of 418 patients who underwent curative resection for stage I to III colon cancer and routinely adopted an elastin stain were evaluated. MAIN OUTCOME MEASURES: Venous invasion detection rate after adopting elastin stain, prognostic factors influencing disease recurrences by multivariate Cox regression models, and survival were measured. The zones of lymph node metastasis were defined as LNZ1, LNZ2, and LNZ3, corresponding to metastases in the pericolic, intermediate, and apical nodes. RESULTS: Venous invasion detection rate increased from 11.3% to 35.4% compared with the previous period in which only hematoxylin and eosin stain was performed. Cox regression analysis showed venous invasion (HR, 3.856; 95% CI, 1.249-11.910; p = 0.019) and lymph node metastases (HR, 3.156; 95% CI, 1.094-9.108; p = 0.034) in all stages and LNZ 2, 3 (HR, 2.649; 95% CI, 1.244-5.640; p = 0.012) in stage III to be significantly associated with poor disease-free survival. When stratifying all patients by these 3 factors, patients with stage III [LNZ1/venous invasion (-)] had disease-free survival comparable with stage I, but significantly better disease-free survival than those with stage II [venous invasion (+)] (p = 0.018). Patients with stage II [venous invasion (+)] had better disease-free survival by using adjuvant chemotherapy (p < 0.001). LIMITATIONS: This study was limited by its retrospective design. CONCLUSION: Elastin stain contributed to a considerable increase in venous invasion detection. Venous invasion can be a powerful predictor of poor disease-free survival beyond lymph node metastases when limited to the pericolic area and is useful for deciding the use of adjuvant chemotherapy in stage II colon cancer. See Video Abstract at http://links.lww.com/DCR/B573. EL VALOR PRONSTICO DE LA INVASIN VENOSA DETECTADA POR LA TINCIN DE ELASTINA PUEDE SUPERAR EL ESTADO DE LOS GANGLIOS LINFTICOS EN EL CNCER DE COLON: ANTECEDENTES:Invasión venosa (IV) es un factor de mal pronóstico en el cáncer de colon, que frecuentemente no se informa con una variabilidad significativa.OBJETIVOS:Nuestro objetivo fue determinar el impacto de tinción de elastina en la detección de IV en el cáncer de colon y evaluar el valor de IV en la predicción de la recurrencia de la enfermedad en combinación con el estado de los ganglios linfáticos y otros factores pronósticos.DISEÑO:Este es un análisis retrospectivo de una base de datos recopilada prospectivamente.ENTORNO CLINICO:Este estudio se realizó en un centro oncológico de referencia de tercer nivel.PACIENTES:Se valoraron un total de 418 pacientes sometidos a resección curativa por cáncer de colon en estadio I-III utilizando de manera rutinaria una tinción de elastina.PRINCIPALES MEDIDAS DE VALORACION:Se midieron la tasa de detección de IV después de adoptar la tinción de elastina, los factores de pronóstico que influyen en las recurrencias de la enfermedad mediante modelos de regresión de Cox multivariados y la supervivencia. La zona de metástasis ganglionares se definió como, LNZ1, LNZ2 y LNZ3, correspondientes a las metástasis en los ganglios pericólicos, intermedios y apicales, respectivamente.RESULTADOS:La tasa de detección de IV aumentó de 11,3% a 35,4% en comparación con el período anterior en el que solo se realizó tinción con hematoxilina y eosina. El análisis de regresión de Cox mostró VI (razón de riesgo, 3.856; intervalo de confianza [IC] del 95%, 1.249-11.910, p = 0.019) y metástasis en los ganglios linfáticos (razón de riesgo, 3.156; IC del 95%, 1.094-9.108, p = 0.034) en todos los estadios y LNZ 2, 3 (cociente de riesgo, 2.649; IC del 95%, 1.244-5.640, p = 0.012) en el estadio III se asociaron significativamente con una pobre supervivencia libre de enfermedad. Al estratificar a todos los pacientes según estos tres factores, los pacientes con estadio III [LNZ1 / VI (-)] tuvieron una sobrevivencia sin enfermedad (SSE) comparable con el estadio I, pero una supervivencia libre de enfermedad significativamente mejor que aquellos con estadio II [VI (+)] (p = 0,018). Pacientes en estadío II [VI (+)] tuvieron una mejor supervivencia sin enfermedad mediante el uso de quimioterapia adyuvante (p <0,001).LIMITACIONES:Estudio limitado por su diseño retrospectivo.CONCLUSIÓN:La tinción de elastina contribuyó a un aumento considerable en la detección de IV. IV puede ser un poderoso predictor de supervivencia sin enfermedad deficiente más allá de las metástasis de los ganglios linfáticos cuando se limita al área pericólica y es útil para decidir el uso de quimioterapia adyuvante en el cáncer de colon en estadío II. Consulte Video Resumen en http://links.lww.com/DCR/B573. (Traducción-Dr. Adrian Ortega).

Initial experience of preoperative short-course radiotherapy followed by oxaliplatin-based consolidation chemotherapy for locally advanced rectal cancer.

PURPOSE: We analyzed the safety and feasibility of preoperative short-course radiotherapy (SCRT) followed by consolidation chemotherapy for patients with locally advanced rectal cancer (LARC). METHODS: From April 2018 to May 2019, 19 patients with LARC were treated with SCRT followed by three cycles of consolidation chemotherapy with leucovorin, fluorouracil, and oxaliplatin (FOLFOX6) before surgery. Adjuvant chemotherapy relied on oxaliplatin. Tumor response, patient compliance, and toxicities were analyzed. RESULTS: The median age was 60 years (range 44-71), and 16 of the patients were male. The median tumor height was 5 cm (range 0-9) from anal verge. All patients received a total dose of 25 Gy in five fractions. The number of cycles of FOLFOX6 before surgery was three in 17, four in one, five in one. Five patients required dose reductions in consolidation chemotherapy. The median interval between initiation of SCRT and surgery was 10.6 weeks (range 8.6-16.4). A pathologic complete response was seen in two patients (11%). Grade III toxicities to the preoperative treatment were seen in five patients (26%): diarrhea in two, a decreased white blood cell count in one, and anemia in two. Postoperative complications arising within 30 days developed in five patients (26%). During the median follow-up period of 20.4 months, there was no tumor recurrence. CONCLUSION: Preoperative SCRT followed by oxaliplatin-based consolidation chemotherapy showed acceptable toxicity and feasibility in patients with LARC. Prospective randomized trials are warranted to verify the efficacy and safety of this treatment strategy compared with conventional long-course concurrent chemoradiotherapy.

Associations between the working experiences at frontline of COVID-19 pandemic and mental health of Korean public health doctors.

BACKGROUND: Demographic, work environmental, and psychosocial features are associated with mental health of healthcare professionals at pandemic frontline. The current study aimed to find predictors of mental health for public health doctors from working experiences at frontline of COVID-19 pandemic. METHODS: With first-come and first-served manner, 350 public health doctors with experiences of work at COVID-19 frontline participated online survey on August 2020. Mental health was defined using the total scores of the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Perceived Stress Scale, and the Stanford Presenteeism Scale-6. Multivariate logistic regression models of mental health with lowest Akaike Information Criterion were determined among all combinations of working environments, perceived threats and satisfaction at frontline, and demographics that were significant (P < 0.05) in the univariate logistic regression. RESULTS: Perceived distress, lowered self-efficacy at work, anxiety, and depressive mood were reported by 45.7, 34.6, 11.4, and 15.1% of respondents, respectively. Predictors of poor mental health found in the multivariate logistic regression analyses were environmental (insufficient personal protective equipment, workplace of screening center, prolonged workhours) and psychosocial (fear of infection and death, social stigma and rejection) aspects of working experiences at frontline. Satisfaction of monetary compensation and proactive coping (acceptance and willingness to volunteer at frontline) were predictive of better mental health. CONCLUSIONS: Sufficient supply of personal protective equipment and training on infection prevention at frontline, proper workhours and satisfactory monetary compensation, and psychological supports are required for better mental health of public health doctors at frontline of COVID-19 pandemic.

Distinct domains of Escherichia coli IgaA connect envelope stress sensing and down-regulation of the Rcs phosphorelay across subcellular compartments.

In enterobacteria, the Rcs system (Regulator of capsule synthesis) monitors envelope integrity and induces a stress response when damages occur in the outer membrane or in the peptidoglycan layer. Built around a two-component system, Rcs controls gene expression via a cascade of phosphoryl transfer reactions. Being particularly complex, Rcs also involves the outer membrane lipoprotein RcsF and the inner membrane essential protein IgaA (Intracellular growth attenuator). RcsF and IgaA, which are located upstream of the phosphorelay, are required for normal Rcs functioning. Here, we establish the stress-dependent formation of a complex between RcsF and the periplasmic domain of IgaA as the molecular signal triggering Rcs. Moreover, molecular dissection of IgaA reveals that its negative regulatory role on Rcs is mostly carried by its first N-terminal cytoplasmic domain. Altogether, our results support a model in which IgaA regulates Rcs activation by playing a direct role in the transfer of signals from the cell envelope to the cytoplasm. This remarkable feature further distinguishes Rcs from other envelope stress response systems.

Genome-Wide Analysis Reveals Mucociliary Remodeling of the Nasal Airway Epithelium Induced by Urban PM2.5.

Air pollution particulate matter <2.5 µm (PM2.5) exposure is associated with poor respiratory outcomes. Mechanisms underlying PM2.5-induced lung pathobiology are poorly understood but likely involve cellular and molecular changes to the airway epithelium. We extracted and chemically characterized the organic and water-soluble components of air pollution PM2.5 samples, then determined the whole transcriptome response of human nasal mucociliary airway epithelial cultures to a dose series of PM2.5 extracts. We found that PM2.5 organic extract (OE), but not water-soluble extract, elicited a potent, dose-dependent transcriptomic response from the mucociliary epithelium. Exposure to a moderate OE dose modified the expression of 424 genes, including activation of aryl hydrocarbon receptor signaling and an IL-1 inflammatory program. We generated an OE-response gene network defined by eight functional enrichment groups, which exhibited high connectivity through CYP1A1, IL1A, and IL1B. This OE exposure also robustly activated a mucus secretory expression program (>100 genes), which included transcriptional drivers of mucus metaplasia (SPDEF and FOXA3). Exposure to a higher OE dose modified the expression of 1,240 genes and further exacerbated expression responses observed at the moderate dose, including the mucus secretory program. Moreover, the higher OE dose significantly increased the MUC5AC/MUC5B gel-forming mucin expression ratio and strongly downregulated ciliated cell expression programs, including key ciliating cell transcription factors (e.g., FOXJ1 and MCIDAS). Chronic OE stimulation induced mucus metaplasia-like remodeling characterized by increases in MUC5AC+ secretory cells and MUC5AC mucus secretions. This epithelial remodeling may underlie poor respiratory outcomes associated with high PM2.5 exposure.

Demonstration of photonics-aided terahertz wireless transmission system with using silicon photonics circuit.

We experimentally demonstrate the use of silicon photonics circuit (SPC) in the simple and cost-effective photonics-aided Terahertz (THz) wireless transmission system. We perform theoretical investigation (with experimental confirmation) to understand that the system performance is more sensitive to the free space path loss (FSPL) at the THz wireless link than the SPC's insertion loss. The SPC, we design and fabricate, combines two incident optical carriers at different wavelengths and modulates one of two optical carriers with data to transfer, consequently reducing the system footprint that is indeed one of the key challenges that must be tackled for better practicability of the THz communication system. We perform experimental verification to show the feasibility of 40 Gb/s non-return-to-zero (NRZ) on-off-keying (OOK) signal transmission over 1.4 m wireless link for possibly its application in short-reach indoor wireless communication systems utilizing (sub-)THz frequency band such as, e.g., indoor WiFi, distributed antenna/radio systems, rack-to-rack data delivery, etc. The SPC could be further integrated with various photonic elements such as semiconductor optical amplifiers, laser diodes, and photo-mixers, which will enable the path towards all-photonic THz-wave synthesizers.

Demonstration of photonics-aided terahertz wireless transmission system with using silicon photonics circuit: erratum.

We present an erratum for our recent paper [Opt. Express 28, 23397 (2020)] to include funding information in the funding section.