A special kind of election is unfolding across Victoria as the Aboriginal communities taking part in the treaty process cast their votes to elect a First Peoples' Assembly.

Although 3D printing is being used for a variety of applications in healthcare, biomedical engineering and manufacturing, it is still pretty limited

When is a lamb a lamb and what difference can it make to the price and the flavour?

Living in Montreal, I often have to create multi-lingual websites for clients. That means finding the right plugin for the job. I don’t always use WPML, but it’s one of…

The post Displaying Different Logos with WPML appeared first on bavotasan.com.

When These Lisbon-based Musicians Perform It’s Not A Show, It’s A Party, And It's Not A Party, It's A Gathering Rua Das Pretas Is A Lisbon-based Gathering Of International Musicians.

When These Lisbon-based Musicians Perform It’s Not A Show, It’s A Party, And It's Not A Party, It's A Gathering Rua Das Pretas Is A Lisbon-based Gathering Of International Musicians.

Collaborative Infrastructure Procurement in Sweden and the Netherlands , released by the International Transport Forum

A report from the Office of the Inspector General at the U.S. Department of Transportation

In contrast to previous notes, in this set of notes we shall focus exclusively on Fourier analysis in the one-dimensional setting for simplicity of notation, although all of the results here have natural extensions to higher dimensions. Depending on the physical context, one can view the physical domain as representing either space or time; we […]

So like most other Jews I took part in virtual seders this year. It was very emotional and mostly good.

In less than a month, it's been amazing how Jewish communities have adapted to being mostly virtual. My home synagogue went from frowning on use of electronics at all on Shabbat and festivals, to unanimous agreement that we're keeping up the livestreaming once we're allowed back in our physical building, and the most vocal objectors to tech have started leading virtual services. Basically, the first time we did it, with great trepidation, we saw the faces of former members who have moved away, even to other continents, and of disabled and chronically ill members who are only variably able to attend shul in person. And suddenly, we all viscerally understood that using telecomms for religious purposes and to be together as a community is honoring the sabbath, not breaking it.

The other factor is that Zoom is good enough. It's not perfect, but the sound and picture quality, and the interoperability across devices, and the usability for people who aren't really tech savvy, are all good enough that you can just get on and have your virtual gathering. Yes, I know there are privacy and security concerns, but honestly I'm a bit impatient with hearing about those problems from people who live most of their online life in the Google empire. (People who are very strictly Free software only I have more sympathy for, but even then, if you're not providing tech support for people using elderly i-devices who can barely use a web browser, or at least working on products that are actually usable by people who haven't been programming since they could read, then my patience is still limited.)

In less than a month, we've gone from, stick a web cam in front of a service and hope, to people actually creating liturgy for distributed video call services. Even including fake Zoom-bombing by 'Pharaoh' refusing to let the people go, or 'Elijah'. What is still missing is the ritual around the Torah scrolls, and anything more than very limited music; my community pride themselves on their beautiful spontaneous harmonies and that's not really happening. But still, it's been amazing, people are praying together from their homes.

So, I agreed with my family that we would do a Zoom-based seder this year (I'm not quite sure about the coinage 'Zeder'). And planning the liturgy was a bit chaotic, but it's kind of always chaotic. We also all realized that actually, a virtual seder has a rather higher limit on how many people can join together, so instead of having two separate occasions for my family of origin and my family of choice, we all piled in to a huge seder, nine households, and my dad's sister and his oldest friend from uni who sometimes used to join us when we were kids. There was this moment when I was trying to introduce everybody who might not know each other, and I wanted to make it clear that my partners are my partners without getting derailed into a complicated poly coming out thing, and I said something kind of clumsy about usually being a family but less so at the moment under quarantine, and my lovely gf said, no, we're just as much family now, only in different physical places. There's a lot of sadness about not being able to gather in person for the one day in the year when we always manage a family reunion no matter what, but that moment went a long way to make up for it.

I struggled a bit with finding an online Hagaddah. I mean, there are a zillion options, but I found few that met my requirements of being relatively easy to use while you also have your fellow guests in their little video grid in another window, containing all the traditional text in a clear layout that distinguishes it from commentary, and not being intolerably sexist. But we made up seder plates as best as we could, with ingenious substitutions in some houses and the family's heirloom china in others. And mostly we could judge whose turn it was to speak, though it's cognitively extremely taxing compared to being at the same table, and we managed to read the essential words and have some discussions, and Judith (who has been learning Hebrew for about one term) sang the four questions. And we sort of managed to hide and hunt for the afikomen. I hadn't been sure about maintaining the Zoom connection while we were eating, but actually about half the houses dropped out and the rest of us remained and managed to chat and catch up and argue politics and even complete the remainder of a mostly finished Times jumbo crossword over Zoom. Very few aspects of a proper seder meal were lacking!

The thing about a virtual seder is, we finished the main ritual at 10, and clearing up for 2 is much quicker than clearing up for 20, and we didn't have to travel home via spending an hour standing in the doorway talking about how we really must get going, so actually we managed quite an early night. And then the morning service, which I basically never make it to, was online rather than in town, so I showed up. Then second night, my Stoke community completely spontaneously organized a virtual community seder, with no input at all from me. Someone else put together a virtual Hagaddah by combining pages from various sources and making a kind of slide-slow, and got everybody to take part in the reading, and did fun stuff for kids (another pupil from the same Hebrew class where I'm teaching my partners' kid did the four questions) the community just showed up and got on with it. A few stayed away because it's an Orthodox community and some followed the Ashkenazi rabbinate's ruling that Zoom seders are forbidden, but it was lovely to see at least some of my people.

And my sister posted me her amazing Pesach cakes, and she and some other people rallied round to make sure I had matzah, and somehow, it's the most terrible Pesach but it's also a really wonderful Pesach. I am loving reading of everybody else's improvised seders, or their first times leading instead of deferring to their elders, or people who took advantage of the virtual seder to be able to be with both sets of inlaws or even relatives who normally can't stand eachother, or the people who are normally too secular but decided that this year they wanted to mark the occasion. And lots lots lots of people have pointed out that it couldn't be more in the spirit of Pesach that we're all improvising what sanctity we can while we huddle from danger. I was particularly moved by jjhunter's haiku and all the responses:

may it pass over
our elders our sick our home
everyone held safe

Perhaps over zoom we will find companionship, or perhaps in the unusual quietness we will create space for the ‘still small voice’. It will be a Passover like no other, but this too shall Pass, and we will have done enough.

Making money online, it seems every day more people are looking ways to make money online either to boost their income as a secondary source of income, or as a full time job. But if you’re relatively new to this how do you make money online? I put together a list of 20 different ways you can make money on the internet. I’ve broken these down into two groups, ways you can make money without a website or blog, and ways you can with a website. These ideas aren’t listed in any order of importance as some of them will work better for you then others.

Onboard Queen VictoriaYou know that feeling you get when you are in your bedroom laying down after just waking up where you have this moment of intense thinking and all you can imagine is how small you are compared to everything else in exi

Ralph Lawler discusses what it's like to see the NBA season suspended, a promising Clippers season put on hold, and the world change while on vacation.

Doesn't really pay for me to be appealing to my captors. They are snarky, and increasingly restless. They pass the long evenings mixing up different flavors of White Claw just for kicks, the way Millennials will.

Julia Alvarez's "Afterlife" is her first novel for adults in 15 years. She talks about loss, fragmentation and "American Dirt."

In Rufi Thorpe's novel, a poor, closeted teenager befriends a wealthy girl, until an act of violence lays their class distinctions bare.

Peer-to-peer car sharing seems strange but turns out to be easy, if a bit expensive.

"Strike," the first feature by Gigglefish Animation Studios, is quirky and charming.

You can’t say that you have travelled until you visit all the continents of the world. If you’re a hardcore traveler, it’s best to explore not only one side of the globe, but all parts...

The post Travel to Different Corners of the World appeared first on Geeky Traveller.

Cone photoreceptors in the retina enable vision over a wide range of light intensities. However, the processes enabling cone vision in bright light (i.e. photopic vision) are not adequately understood. Chromophore regeneration of cone photopigments may require the retinal pigment epithelium (RPE) and/or retinal Müller glia. In the RPE, isomerization of all-trans-retinyl esters to 11-cis-retinol is mediated by the retinoid isomerohydrolase Rpe65. A putative alternative retinoid isomerase, dihydroceramide desaturase-1 (DES1), is expressed in RPE and Müller cells. The retinol-isomerase activities of Rpe65 and Des1 are inhibited by emixustat and fenretinide, respectively. Here, we tested the effects of these visual cycle inhibitors on immediate, early, and late phases of cone photopic vision. In zebrafish larvae raised under cyclic light conditions, fenretinide impaired late cone photopic vision, while the emixustat-treated zebrafish unexpectedly had normal vision. In contrast, emixustat-treated larvae raised under extensive dark-adaptation displayed significantly attenuated immediate photopic vision concomitant with significantly reduced 11-cis-retinaldehyde (11cRAL). Following 30 min of light, early photopic vision was recovered, despite 11cRAL levels remaining significantly reduced. Defects in immediate cone photopic vision were rescued in emixustat- or fenretinide-treated larvae following exogenous 9-cis-retinaldehyde supplementation. Genetic knockout of Des1 (degs1) or retinaldehyde-binding protein 1b (rlbp1b) did not eliminate photopic vision in zebrafish. Our findings define molecular and temporal requirements of the nonphotopic or photopic visual cycles for mediating vision in bright light.

Nucleoside analogues are a valuable experimental tool. Incorporation of these molecules into newly synthesized DNA (i.e. pulse-labeling) is used to monitor cell proliferation or to isolate nascent DNA. Some of the most common nucleoside analogues used for pulse-labeling of DNA in cells are the deoxypyrimidine analogues 5-ethynyl-2'-deoxyuridine (EdU) and 5-ethynyl-2'-deoxycytidine (EdC). Click chemistry enables conjugation of an azide molecule tagged with a fluorescent dye or biotin to the alkyne of the analog, which can then be used to detect incorporation of EdU and EdC into DNA. The use of EdC is often recommended because of the potential cytotoxicity associated with EdU during longer incubations. Here, by comparing the relative incorporation efficiencies of EdU and EdC during short 30-min pulses, we demonstrate significantly lower incorporation of EdC than of EdU in noninfected human fibroblast cells or in cells infected with either human cytomegalovirus or Kaposi's sarcoma-associated herpesvirus. Interestingly, cells infected with herpes simplex virus type-1 (HSV-1) incorporated EdC and EdU at similar levels during short pulses. Of note, exogenous expression of HSV-1 thymidine kinase increased the incorporation efficiency of EdC. These results highlight the limitations when using substituted pyrimidine analogues in pulse-labeling and suggest that EdU is the preferable nucleoside analogue for short pulse-labeling experiments, resulting in increased recovery and sensitivity for downstream applications. This is an important discovery that may help to better characterize the biochemical properties of different nucleoside analogues with a given kinase, ultimately leading to significant differences in labeling efficiency of nascent DNA.

The arrangement of functionally-related genes in operons is a fundamental element of how genetic information is organized in prokaryotes. This organization ensures coordinated gene expression by co-transcription. Often, however, alternative genetic responses to specific stress conditions demand the discoordination of operon expression. During cold temperature stress, accumulation of the gene encoding the sole Asp–Glu–Ala–Asp (DEAD)-box RNA helicase in Synechocystis sp. PCC 6803, crhR (slr0083), increases 15-fold. Here, we show that crhR is expressed from a dicistronic operon with the methylthiotransferase rimO/miaB (slr0082) gene, followed by rapid processing of the operon transcript into two monocistronic mRNAs. This cleavage event is required for and results in destabilization of the rimO transcript. Results from secondary structure modeling and analysis of RNase E cleavage of the rimO–crhR transcript in vitro suggested that CrhR plays a role in enhancing the rate of the processing in an auto-regulatory manner. Moreover, two putative small RNAs are generated from additional processing, degradation, or both of the rimO transcript. These results suggest a role for the bacterial RNA helicase CrhR in RNase E-dependent mRNA processing in Synechocystis and expand the known range of organisms possessing small RNAs derived from processing of mRNA transcripts.

JM Dietschy
Oct 1, 1993; 34:1637-1659
Reviews

DL Brasaemle
Nov 1, 1997; 38:2249-2263
Articles

The arrangement of functionally-related genes in operons is a fundamental element of how genetic information is organized in prokaryotes. This organization ensures coordinated gene expression by co-transcription. Often, however, alternative genetic responses to specific stress conditions demand the discoordination of operon expression. During cold temperature stress, accumulation of the gene encoding the sole Asp–Glu–Ala–Asp (DEAD)-box RNA helicase in Synechocystis sp. PCC 6803, crhR (slr0083), increases 15-fold. Here, we show that crhR is expressed from a dicistronic operon with the methylthiotransferase rimO/miaB (slr0082) gene, followed by rapid processing of the operon transcript into two monocistronic mRNAs. This cleavage event is required for and results in destabilization of the rimO transcript. Results from secondary structure modeling and analysis of RNase E cleavage of the rimO–crhR transcript in vitro suggested that CrhR plays a role in enhancing the rate of the processing in an auto-regulatory manner. Moreover, two putative small RNAs are generated from additional processing, degradation, or both of the rimO transcript. These results suggest a role for the bacterial RNA helicase CrhR in RNase E-dependent mRNA processing in Synechocystis and expand the known range of organisms possessing small RNAs derived from processing of mRNA transcripts.

V. V. Vlasov and N. A. Rautian
Trans. Moscow Math. Soc. 80 (2020), 169-188.
Abstract, references and article information

N. F. Valeev, Ya. T. Sultanaev and É. A. Nazirova
Trans. Moscow Math. Soc. 80 (2020), 153-167.
Abstract, references and article information

K. A. Mirzoev and T. A. Safonova
Trans. Moscow Math. Soc. 80 (2020), 133-151.
Abstract, references and article information

Long Chen and Xuehai Huang
Math. Comp. 89 (2019), 1711-1744.
Abstract, references and article information

S. V. Bodnarchuk and O. M. Kulyk
Theor. Probability and Math. Statist. 99 (2020), 53-65.
Abstract, references and article information

N. Kuznetsov
St. Petersburg Math. J. 31 (2020), 521-531.
Abstract, references and article information

Nucleoside analogues are a valuable experimental tool. Incorporation of these molecules into newly synthesized DNA (i.e. pulse-labeling) is used to monitor cell proliferation or to isolate nascent DNA. Some of the most common nucleoside analogues used for pulse-labeling of DNA in cells are the deoxypyrimidine analogues 5-ethynyl-2'-deoxyuridine (EdU) and 5-ethynyl-2'-deoxycytidine (EdC). Click chemistry enables conjugation of an azide molecule tagged with a fluorescent dye or biotin to the alkyne of the analog, which can then be used to detect incorporation of EdU and EdC into DNA. The use of EdC is often recommended because of the potential cytotoxicity associated with EdU during longer incubations. Here, by comparing the relative incorporation efficiencies of EdU and EdC during short 30-min pulses, we demonstrate significantly lower incorporation of EdC than of EdU in noninfected human fibroblast cells or in cells infected with either human cytomegalovirus or Kaposi's sarcoma-associated herpesvirus. Interestingly, cells infected with herpes simplex virus type-1 (HSV-1) incorporated EdC and EdU at similar levels during short pulses. Of note, exogenous expression of HSV-1 thymidine kinase increased the incorporation efficiency of EdC. These results highlight the limitations when using substituted pyrimidine analogues in pulse-labeling and suggest that EdU is the preferable nucleoside analogue for short pulse-labeling experiments, resulting in increased recovery and sensitivity for downstream applications. This is an important discovery that may help to better characterize the biochemical properties of different nucleoside analogues with a given kinase, ultimately leading to significant differences in labeling efficiency of nascent DNA.

Vladimir Dragović and Irina Goryuchkina
Bull. Amer. Math. Soc. 57 (2020), 293-299.
Abstract, references and article information

Back in January when dancehall artiste Govana released the track HAMANTS Convo, the storyline captivated listeners across the globe. For weeks, the song, which highlights infidelity in relationships, trended at number one on the local YouTube...

Yafeng Zhu
Mar 23, 2020; 0:TIR119.001646v1-mcp.TIR119.001646
Technological Innovation and Resources

Purpose: ⁶⁸Ga-DOTA-JR11 is an antagonist for somatostatin receptor used in neuroendocrine imaging. The purpose of this study is to compare ⁶⁸Ga-DOTA-JR11 and ⁶⁸Ga-DOTATATE PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors. Methods: Patients with histologically-proven, metastatic and/or unresectable, well-differentiated neuroendocrine tumors were prospectively recruited in this study. They received an intravenous injection of ⁶⁸Ga-DOTATATE (4.0 ± 1.3 mCi) on the first day and ⁶⁸Ga-DOTA-JR11 (4.0 ± 1.4 mCi) on the second day. Whole-body PET/CT scans were performed at 40 to 60 minutes after injection on the same scanner. Physiologic uptake of normal organs, lesion numbers, and lesion uptake were compared. Results: Twenty-nine patients were prospectively enrolled in the study. The SUV_max of the spleen, renal cortex, adrenal glands, pituitary glands, stomach wall, normal liver parenchyma, small intestine, pancreas, and bone marrow were significantly lower on ⁶⁸Ga-DOTA-JR11 than on ⁶⁸Ga-DOTATATE PET/CT (P<0.001). ⁶⁸Ga-DOTA-JR11 detected significantly more liver lesions (539 vs. 356, P = 0.002), but fewer bone lesions (156 vs. 374, P = 0.031, Figure 3) than ⁶⁸Ga-DOTATATE. The tumor-to-background ratio of liver lesions was significantly higher on ⁶⁸Ga-DOTA-JR11 (7.6 ± 5.1 vs. 3.4 ± 2.0, P<0.001). ⁶⁸Ga-DOTA-JR11 and ⁶⁸Ga-DOTATATE PET/CT showed comparable results for primary tumors and lymph node metastases based on either patient-based or lesion-based comparison. Conclusion: ⁶⁸Ga-DOTA-JR11 performs better in the detection ability and TBR of liver metastases. However, ⁶⁸Ga-DOTATATE outperforms ⁶⁸Ga-DOTA-JR11 in the detection of bone metastases. The differential affinity of different metastatic sites provides key information for patient selection in imaging and peptide receptor radionuclide therapy.

Purpose: Although the incidence of de novo neuroendocrine prostate cancer (NEPC) is rare, recent data suggests that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine (NE) hallmarks and androgen receptor (AR)-suppression in prostate cancer (PC). Previous clinical reports indicate that PCs with a phenotype similar to NE tumors can be more amenable to imaging by ¹⁸F-Fluorodeoxyglucose (FDG) rather than PSMA-targeting radioligands. In this study, we evaluated the association between NE gene signature and FDG uptake-associated genes including glucose transporters (GLUTs) and hexokinases, with the goal of providing a genomic signature to explain the reported FDG-avidity of PSMA-suppressed tumors. Methods: Data mining approaches, cell lines and patient-derived xenograft (PDX) models were used to study the levels of 14 members of the SLC2A family (encoding GLUT proteins), 4 members of the hexokinase family (genes: HK1 to 3 and GCK) and PSMA (FOLH1 gene) following AR-inhibition and in correlation with NE hallmarks. Also, we characterize a NE-like PC (NELPC) subset among a cohort of primary and metastatic PC samples with no NE histopathology. We measured glucose uptake in a NE-induced in vitro model and a zebrafish model by non-radioactive imaging of glucose uptake using fluorescent glucose bioprobe, GB2-Cy3. Results: This work demonstrates that a NE gene signature associates with differential expression of genes encoding GLUT and hexokinase proteins. In NELPC, elevated expression of GCK (encoding glucokinase protein) and decreased expression of SLC2A12 correlated with earlier biochemical recurrence. In tumors treated with AR-inhibitors, high expression of GCK and low expression of SLC2A12 correlated with NE histopathology and PSMA gene suppression. GLUT12-suppression and amplification of glucokinase was observed in NE-induced PC cell lines and PDX models. A higher glucose uptake was confirmed in low-PSMA tumors using a GB2-Cy3 probe in a zebrafish model. Conclusion: NE gene signature in NEPC and NELPC associates with a distinct transcriptional profile of GLUTs and HKs. PSMA-suppression correlates with GLUT12-suppression and glucokinase-amplification. Alteration of FDG uptake-associated genes correlated positively with higher glucose uptake in AR and PSMA-suppressed tumors. Zebrafish xenograft tumor models are an accurate and efficient pre-clinical method for monitoring non-radioactive glucose uptake.

Introduction: Neuroendocrine differentiation is associated with treatment failure and poor outcome in metastatic castration-resistant prostate cancer (mCRPC). We investigated the effect of circulating neuroendocrine biomarkers on the efficacy of PSMA-targeted radioligand therapy (RLT). Methods: Neuroendocrine biomarker profiles (progastrin-releasing peptide, neuron-specific enolase, and chromogranin-A) were analyzed in 50 patients commencing ¹⁷⁷Lu-PSMA-617 RLT. The primary endpoint was PSA response in relation to baseline neuroendocrine marker profiles. Additional endpoints included progression-free survival. Tumor uptake on post-therapeutic scans, a known predictive marker for response, was used as control-variable. Results: Neuroendocrine biomarker profiles were abnormal in the majority of patients. Neuroendocrine biomarker levels did not predict treatment failure or early progression (P ≥ 0.13). By contrast, intense PSMA-ligand uptake in metastases predicted both treatment response (P = 0.0030) and reduced risk of early progression (P = 0.0111). Conclusion: Neuroendocrine marker profiles do not predict adverse outcome of RLT. By contrast, high ligand uptake was confirmed to be crucial for achieving tumor-response.

Rationale: Neuroinflammation has been implicated in Amyotrophic Lateral Sclerosis (ALS) and can be visualized using translocator protein (TSPO) radioligands. To become a reliable pharmacodynamic biomarker for ALS multicenter trials, some challenges have to be overcome. We aimed to investigate whether multicenter data pooling of different TSPO tracers (¹¹C-PBR28 and ¹⁸F-DPA714) is feasible, after validation of an established ¹¹C-PBR28 PET pseudoreference analysis technique for ¹⁸F-DPA714. Methods: 7 ALS-Belgium (58.9±6.7 years,5M) and 8 HV-Belgium (52.1±15.2 years,3M); and 7 ALS-US (53.4±9.8 years,5M) and 7 HV-US (54.6±9.6 years,4M) from a previously published study (1) underwent dynamic ¹⁸F-DPA714 (Leuven, Belgium) or ¹¹C-PBR28 (Boston, US) PET-MR scans. For ¹⁸F-DPA714, volume of distribution (VT) maps were compared to standardized uptake value ratios (SUVR)40-60 calculated using the pseudoreference regions (1)cerebellum, (2)occipital cortex, and (3)whole brain without ventricles (WB-ventricles). Also for ¹¹C-PBR28, SUVR60-90 using WB-ventricles were calculated. Results: In line with previous studies, increased ¹⁸F-DPA714 uptake (17.0±5.6%) in primary motor cortices was observed in ALS, as measured by both VT and SUVR40-60 approaches. Highest sensitivity was found for SUVRWB-ventricles (average cluster 21.6±0.1%). ¹⁸F-DPA714 VT ratio and SUVR40-60 results were highly correlated (r>0.8, p<0.001). A similar pattern of increased uptake (average cluster 20.5±0.5%) in primary motor cortices was observed in ALS with ¹¹C-PBR28 using the SUVRWB-ventricles. Analysis of the ¹⁸F-DPA714 and ¹¹C-PBR28 data together, resulted in a more extensive pattern of significant increased glial activation in the bilateral primary motor cortices. Conclusion: The same pseudoreference region analysis technique for ¹¹C-PBR28 PET imaging can be extended towards ¹⁸F-DPA714 PET. Therefore, in ALS, standardized analysis across these two tracers enables pooling of TSPO PET data across multiple centers and increase power of TSPO as biomarker for future therapeutic trials.

Purpose: We aimed to conduct a systematic review and meta-analysis of studies reporting the performance of radioactive iodine therapy (131-I therapy) in differentiating thyroid cancer (DTC) patients requiring a completion treatment following lobectomy. We also evaluated the response to 131-I therapy according to 2015ATA guidelines and the adverse events. Methods: A specific search strategy was designed to find articles evaluating the use of I-131 in patients with evidence of DTC after lobectomy. PubMed, CENTRAL, Scopus and Web of Science were searched. The search was updated until January 2020, without language restriction. Data were cross-checked and any discrepancy discussed. A proportion meta-analysis (with 95%CI) was performed using the random-effects model. Meta-regressions on I-131 success were attempted. Results: The pooled success ablation rate was 69% with better results in patients receiving a single administration of about 3.7 GBq; high heterogeneity was found (I2 85%), and publication bias was absent (Egger test: P = 0.57). Incomplete structural responses were recorded in only 14 of 695 (2%) patients enrolled in our analysis. Incomplete biochemical responses were observed in 8 to 24% of patients, with higher rates (24%) in patients receiving low radioiodine activities (~1.1 GBq) and lower rates (from 8 to 18%) in patients receiving higher activities of radioiodine (~3.7 Gbq). Neck pain due to thyroiditis was reported in up to 18% of patients but, in most cases, symptoms resolved after oral paracetamol or a short course of prednisone. Conclusion: Lobar ablation with 131-I is effective especially when high ¹³¹I activities are used. However, the rate of incomplete biochemical response to initial treatment appears to be slightly higher than the classical scheme of initial treatment of DTC. "Radioisotopic lobectomy" should be considered for patients with low-to-intermediate risk DTC requiring completion treatment after lobectomy due to specific individual risk factors and/or patient’s preferences.

Background: The management for totally thyroidectomized differentiated thyroid cancer (TT-DTC) patients with unexplained hyperthyroglobulinemia remains indeterminate due to evidence scarcity. This multicenter study aimed at prospectively evaluating the response to radioiodine (¹³¹I) adjuvant therapy (RAT) and its potential role in risk stratification and causal clarification. Methods: TT-DTC patients with stimulated serum thyroglobulin (Tgoff) levels > 10 ng/mL but no structurally evident disease were consecutively enrolled in five tertiary care institutions. After the administration of 5.55 GBq of ¹³¹I, the risk of presence of persistent/recurrent/metastatic DTC (prmDTC) was compared to that before RAT. The causes of hyperthyroglobulinemia were explored and the response to RAT was assessed 6-12 months post RAT. The change in suppressed thyroglobulin (Tgon) level was reported. Results: A cohort of 254 subjects with a median Tgoff of 27.1 ng/mL was enrolled for the analyses. Immediately after RAT, low-, intermediate-, and high-risk were identified in 5.9%, 88.6%, and 5.5% patients, respectively, with no significant difference in risk stratification compared with that before RAT (P = 0.952). During the follow-up (median, 10.6 months), hyperthyroglobulinemia was ultimately attributed to thyroid remnant, biochemical disease, and structural/functional disease in 17.3%, 54.3%, and 28.3% of subjects, respectively. In addition, excellent, indeterminate, biochemical incomplete, and structural/functional incomplete responses were achieved in 18.1%, 27.2%, 36.2%, and 18.5% of patients, respectively. Notably, distribution for either cause of hyperthyroglobulinemia or response to RAT was comparable among the three postoperative risk groups. Tgon levels in patients who merely received RAT declined significantly over time. Conclusion: Our study demonstrated that over 90% of TT-DTC patients with unexplained hyperthyroglobulinemia are stratified as intermediate-high risk, and RAT using 5.55 GBq of ¹³¹I reveals biochemical/functional/structural disease and yields non-structural/functional incomplete response in more than 80% patients, suggesting TT-DTC patients with unexplained hyperthyroglobulinemia as explicit candidates for RAT.