Significance Seeds are complex structures that are comprised of the embryo, endosperm, and seed coat. Despite their importance for food, fiber, and fuel, the cellular processes that characterize ...different regions of the seed are not known. We profiled gene activity genome-wide in every organ, tissue, and cell type of Arabidopsis seeds from fertilization through maturity. The resulting mRNA datasets provide unique insights into the cellular processes that occur in understudied seed regions, revealing unexpected overlaps in the functional identities of seed regions and enabling predictions of gene regulatory networks. This dataset is an essential resource for studies of seed biology.
NEJ002 study, comparing gefitinib with carboplatin (CBDCA) and paclitaxel (PTX; Taxol) as the first-line treatment for advanced non-small cell lung cancer (NSCLC) harboring an epidermal growth factor ...receptor (EGFR) mutation, previously reported superiority of gefitinib over CBDCA/PTX on progression-free survival (PFS). Subsequent analysis was carried out mainly regarding overall survival (OS).
For all 228 patients in NEJ002, survival data were updated in December, 2010. Detailed information regarding subsequent chemotherapy after the protocol treatment was also assessed retrospectively and the impact of some key drugs on OS was evaluated.
The median survival time (MST) was 27.7 months for the gefitinib group, and was 26.6 months for the CBDCA/PTX group (HR, 0.887; P=0.483). The OS of patients who received platinum throughout their treatment (n=186) was not statistically different from that of patients who never received platinum (n=40). The MST of patients treated with gefitinib, platinum, and pemetrexed (PEM) or docetaxel (DOC, Taxotere; n=76) was around 3 years.
No significant difference in OS was observed between gefitinib and CBDCA/PTX in the NEJ002 study, probably due to a high crossover use of gefitinib in the CBDCA/PTX group. Considering the many benefits and the risk of missing an opportunity to use the most effective agent for EGFR-mutated NSCLC, the first-line gefitinib is strongly recommended.
EGFR-TKI therapy produces a dramatic clinical response in patients with NSCLC harboring EGFR mutation. However, clinical outcomes should be improved further in this cohort. Thus, we conducted a ...randomized phase II study to investigate the efficacy and safety of combinational EGFR-TKI and chemotherapy, demonstrating that the combination might be a promising strategy for advanced EGFR-mutant NSCLC.
The first-line combination of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) and platinum-based doublet chemotherapy has not been sufficiently evaluated for patients with EGFR-mutant non-small cell lung cancer (NSCLC). This randomized phase II study was designed to select a combination regimen for phase III evaluation.
Chemotherapy-naïve patients with advanced non-squamous, EGFR-mutant NSCLC were randomly assigned to receive either a concurrent or a sequential alternating regimen with gefitinib (250 mg) and carboplatin/pemetrexed area under the curve (AUC) = 6 and 500 mg/m2; 3-weekly. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), response, and safety.
All 80 patients enrolled were eligible and assessable for efficacy (41 and 39 patients in the concurrent and sequential alternating regimen groups, respectively). Median PFS was 18.3 months for the concurrent regimen and 15.3 months for the sequential alternating regimen hazard ratio (HR) 0.71 (0.42–1.20), P = 0.20. Although OS data are immature (16 and 24 death events), median survival times were 41.9 and 30.7 months in the concurrent and sequential alternating regimen groups, respectively HR 0.51 (0.26–0.99); P = 0.042. Response rates were similar in both groups (87.8% and 84.6%). Hematological and non-hematological adverse events were common and reversible; interstitial lung disease was neither frequent nor fatal (two cases in each group; 5% of all patients).
This is the first randomized study to investigate the efficacy of combinational EGFR-TKI and chemotherapy in the EGFR-mutated setting. Both regimens had promising efficacy with predictable toxicities, although concurrent regimens might provide better OS. The concurrent regimen was chosen to compare with gefitinib monotherapy in our ongoing phase III study.
University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN C000002789).
Treating neuropathic pain is challenging and novel non-opioid-based medicines are needed. Using unbiased receptomics, transcriptomic analyses, immunofluorescence, and in situ hybridization, we found ...that the expression of the orphan GPCR Gpr160 and GPR160 increased in the rodent dorsal horn of the spinal cord following traumatic nerve injury. Genetic and immunopharmacological approaches demonstrated that GPR160 inhibition in the spinal cord prevented and reversed neuropathic pain in male and female rodents without altering normal pain response. GPR160 inhibition in the spinal cord attenuated sensory processing in the thalamus, a key relay in the sensory discriminative pathways of pain. We also identified cocaine- and amphetamine-regulated transcript peptide (CARTp) as a GPR160 ligand. Inhibiting endogenous CARTp signaling in spinal cord attenuated neuropathic pain, whereas exogenous intrathecal CARTp evoked painful hypersensitivity through GPR160-dependent ERK and cAMP response element-binding protein (CREB). Our findings de-orphanize GPR160, identify it as a determinant of neuropathic pain and potential therapeutic target, and provide insights into its signaling pathways. CARTp is involved in many diseases including depression and reward and addiction; de-orphanization of GPR160 is a major step forward understanding the role of CARTp signaling in health and disease.
Objectives:
Public Health Reports (PHR), the official journal of the Office of the US Surgeon General and US Public Health Service, is the oldest public health journal in the United States. ...Considering its heritage through the eyes of its past editors in chief (EICs), many of whom have been influential public health figures, can provide a fresh point of view on US public health history, of which the journal has been an integral part. Here, we reconstruct the timeline of past PHR EICs and identify women among them.
Methods:
We reconstructed the PHR EIC timeline by reviewing the journal’s previous mastheads and its articles describing leadership transitions. For each EIC, we identified dates in office, concurrent job titles, key contributions, and other important developments.
Results:
PHR had 25 EIC transitions in 109 years of its history, during which a single individual in charge of the journal could be identified. Only 5 identifiable EICs were women, who served as EIC for approximately one-quarter of the journal’s traceable history (28 of 109 years). PHR’s longest-serving EIC was a woman named Marian P. Tebben (1974-1994).
Conclusions:
PHR history revealed frequent EIC transitions and a low representation of women among its EICs. Mapping the timeline of past EICs of a historic public health journal can yield valuable insights into the workings of US public health, especially in the area of building a research evidence base.
Summary
Background
Bariatric surgery leads to a higher remission rate for type 2 diabetes mellitus than non‐surgical treatment. However, it remains unsolved which surgical procedure is the most ...efficacious. This network meta‐analysis aimed to rank surgical procedures in terms of diabetes remission.
Methods and findings
We electronically searched for randomized controlled trials in which at least one surgical treatment was included among multiple arms and the diabetes remission rate was included in study outcomes. A random‐effects network meta‐analysis was performed within a frequentist framework. The hierarchy of treatments was expressed as the surface under the cumulative ranking curve value. Results of the analysis of 25 eligible randomized controlled trials that covered non‐surgical treatments and eight surgical procedures (biliopancreatic diversion BPD, BPD with duodenal switch, Roux‐en Y gastric bypass, mini gastric bypass mini‐GBP, laparoscopic adjustable gastric banding, laparoscopic sleeve gastrectomy, greater curvature plication and duodenal‐jejunal bypass) showed that BPD and mini‐GBP had the highest surface under the cumulative ranking curve values among the eight surgical treatments.
Conclusion
Current network meta‐analysis indicated that BPD or mini‐GBP achieved higher diabetes remission rates than the other procedures. However, the result needs to be interpreted with caution considering that these procedures were in the minority of bariatric surgeries.
Aim
The anatomy of the region between the vagina and anal canal plays an essential role when performing a proctectomy for low‐lying tumours. However, the anatomical characteristics of this area ...remain unclear. The purpose of the present study was to clarify the configuration, and both lateral and inferior extensions, of the muscle bundles in the anorectal anterior wall in females.
Methods
Using cadaveric specimens, macroscopic anatomical and histological evaluations were conducted at the anatomy department of our institute. Macroscopic anatomical specimens were obtained from six female cadavers. Histological specimens were obtained from eight female cadavers.
Results
The smooth muscle fibres of the internal anal sphincter and longitudinal muscle extended anteriorly in the anorectal anterior wall of females and the muscle bundles showed a convergent structure. The anterior extending smooth muscle fibres merged into the vaginal smooth muscle layer, distributed subcutaneously in the vaginal vestibule and perineum and spread to cover the anterior surface of the external anal sphincter and the levator ani muscle. Relatively sparse space was observed in the region anterolateral to the rectum on histological analysis.
Conclusion
Smooth muscle fibres of the rectum and vagina are intermingled in the median plane, and there is relatively sparse space in the region anterolateral to the rectum. Therefore, when detaching the anorectal canal from the vagina during proctectomy, an approach from both the lateral sides should be used.
Anaplastic lymphoma kinase (ALK) fusions need to be accurately and efficiently detected for ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) remains the reference test. Although ...increasing data are supporting that ALK immunohistochemistry (IHC) is highly concordant with FISH, IHC screening needed to be clinically and prospectively validated.
In the AF-001JP trial for alectinib, 436 patients were screened for ALK fusions through IHC (n = 384) confirmed with FISH (n = 181), multiplex RT-PCR (n = 68), or both (n = 16). IHC results were scored with iScore.
ALK fusion was positive in 137 patients and negative in 250 patients. Since the presence of cancer cells in the samples for RT-PCR was not confirmed, ALK fusion negativity could not be ascertained in 49 patients. IHC interpreted with iScore showed a 99.4% (173/174) concordance with FISH. All 41 patients who had iScore 3 and were enrolled in phase II showed at least 30% tumor reduction with 92.7% overall response rate. Two IHC-positive patients with an atypical FISH pattern responded to ALK inhibitor therapy. The reduction rate was not correlated with IHC staining intensity.
Our study showed (i) that when sufficiently sensitive and appropriately interpreted, IHC can be a stand-alone diagnostic for ALK inhibitor therapies; (ii) that when atypical FISH patterns are accompanied by IHC positivity, the patients should be considered as candidates for ALK inhibitor therapies, and (iii) that the expression level of ALK fusion is not related to the level of response to ALK inhibitors and is thus not required for patient selection.
JapicCTI-101264 (This study is registered with the Japan Pharmaceutical Information Center).
We present a wireless link system that uses millimeter-wave (MMW) photonic techniques. The photonic transmitter in the wireless link consists of an optical 120-GHz MMW generator, an optical ...modulator, and a high-power photonic MMW emitter. A uni-traveling carrier photodiode (UTC-PD) was used as the photonic emitter in order to eliminate electronic MMW amplifiers. We evaluated the dependence of UTC-PD output power on its transit-time limited bandwidth and its CR-time constant limited bandwidth, and employed a UTC-PD with the highest output power for the photonic emitter. As for the MMW generation, we developed a 120-GHz optical MMW generator that generates a pulse train and one that generates a sinusoidal signal. The UTC-PD output power generated by a narrow pulse train was higher than that generated by sinusoidal signals under the same average optical power condition, which contributes to reducing the photocurrent of the photonic emitter. We have experimentally demonstrated that the photonic transmitter can transmit data at up to 3.0 Gb/s. The wireless link using the photonic transmitter can be applied to optical gigabit Ethernet signals.
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