bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radioactive iodine therapy dose impact on recurrence and survival in N1 papillary thyroid cancer
Authors: Odil Elizabeth E. , Ward Katelyn R. , Davis Ryan T. , Reilly Jordan M. , Sun Fionna , Elassar Heba , Lapkus Morta , Pastewski Jacquelyn , Studzinski Diane M. , Callahan Rose E. , Czako Peter F. , Nagar Sapna 
Published: November 2024

Objective
The objective of this study is to investigate radioactive iodine therapy (RAIT) dose impact on survival and recurrence in patients with papillary thyroid cancer (PTC) with regional lymph node metastasis (N1).

Methods
A retrospective study of PTC patients with N1 disease from 2007 to 2011 at a tertiary academic hospital collected demographics, tumor characteristics, and RAIT treatment dose. RAIT dose was stratified by total dosage less than or greater than 150 mCi. Outcomes included recurrence, immediate RAIT side-effects, and mortality.

Results
A total of 60 N1a and 21 N1b patients were studied with a median follow-up of about 9 years. No statistically significant differences were found between N1a PTC patients who received high-dose vs low-dose RAIT in recurrence rate (6.9% vs 6.7%, P > 0.999) or immediate RAIT side effects (6.9% vs 16.1%, P = 0.426). There were no mortalities in the N1a group. For patients with N1b PTC, there were no differences between high-dose and low-dose RAIT in recurrence rate (41.7% vs 44.4%, P > 0.999), mortality (0% vs 16.7%, P = 0.375), or immediate RAIT side effects (8.3% vs 11.1%, P > 0.999).

Conclusion
Dosages of RAIT ≥ 150 mCi do not appear to provide additional benefit in reducing recurrence compared to doses <150 mCi for N1a or N1b PTC patients. No differences in mortality or immediate RAIT side effects were observed between the two dosing regimens; however, interpretation is limited by low event rates. Large randomized trials are needed for further individualized recommendations regarding optimal RAIT dosage in N1 PTC.
Prostatectomy and other local treatments for oligometastatic prostate cancer: recent and ongoing trials
Authors: Fang Andrew M. , MacDonald Landan P. , Gregg Justin R. , Siddiqui Bilal A. , Tang Chad , Chapin Brian F. 
Published: November 2024

Purpose of review
Oligometastatic prostate cancer (OMPCa) is an intermediary state between localized and disseminated metastatic disease that has historically been treated with androgen deprivation therapy (ADT) and more recently with additional systemic therapies in combinations. However, cytoreductive control of the primary tumor may offer an opportunity to control the disease and enhance the response from systemic treatment. In this review, the use of local therapy to the prostate including cytoreductive prostatectomy (CRP), whole pelvis radiotherapy (RT), and focal therapies will be evaluated in the treatment of patients with newly diagnosed OMPCa.

Recent findings
Retrospective studies have demonstrated that some patients with OMPCa may indeed benefit from CRP. With preliminary trials demonstrating that CRP is safe and feasible, there are several phase II and III trials that are currently underway to investigate the role of CRP among patients with OMPCa. Results from several clinical trials have demonstrated that RT and ADT may benefit patients with OMPCa. Lastly, the evidence for focal and cryotherapy remains limited and further clinical trials are required.

Summary
OMPCa is a unique disease state that may benefit from local therapy to the primary tumor. Further study is required to guide treatment selection and patient candidacy. Several trials specifically are awaited to better define the treatment options for patients.
Use and Perceptions of Mobile Mental Health Applications Among Healthcare Workers in Saudi Arabia
Authors: Almadani Ahmad H. , Aldawood Buthainah D. , Alahmari Faysal M. , AbuDujain Nasser M. , Otayf Mojahed M. 
Published: November 2024

Abstract
The use and perceptions of smartphone-based mental health applications (MH-Apps) in Saudi Arabia require exploration. This study investigated MH-App use among Saudi Arabian healthcare workers (HCWs), including psychiatrists, psychologists, and family medicine physicians. It also assessed HCWs' interest in and willingness to integrate these apps into their practices, as well as their cognitive flexibility and its relationship with their attitudes and app use. This cross-sectional study involved 386 participants recruited using convenience and snowball sampling. The Cognitive Flexibility Scale (CFS) was used to assess cognitive flexibility. The results showed that 33.2% of HCWs downloaded MH-Apps, with 67.9% considering them somewhat beneficial. However, most had not yet tried them. Only 7% of HCWs strongly agreed that these apps are evidence-based. Concerns about using these apps in their practices were reported by 36.5% of HCWs, with the most common concern being the lack of evidence-based support. The primary reason for downloading MH-Apps for personal use was to improve mental well-being, whereas patient-related use was psychoeducation. Furthermore, 27.5% of HCWs recommended MH-Apps to their patients, with old age, women, and psychiatrists/psychologists more likely to recommend them. Higher CFS scores were more strongly associated with older HCWs, those who had ever recommended MH-Apps, and those who used the apps. Saudi Arabian HCWs should be encouraged to use and recommend MH-Apps, with more evidence-based research needed to address concerns. Further research on cognitive flexibility's implications for clinical practice is also warranted.
Stage-specific CAR-mediated signaling generates naïve-like, TCR-null CAR T cells from induced pluripotent stem cells
Authors: Yoo Sang Pil , Yuan Xuegang , Engstrom Claire , Chang Patrick , Li Suwen , Lathrop Lindsay , Lagosh Jessica , Seet Christopher , Kohn Donald B. , Crooks Gay M. 
Published: November 2024

AbstractGenetically modified, induced pluripotent stem cells (iPSCs) offer a promising allogeneic source for the generation of functionally enhanced, chimeric antigen receptor (CAR) T cells. However, the signaling of CARs during early T cell development and the removal of the endogenous T cell receptor required to prevent alloreactivity pose significant challenges to the production of mature conventional CAR T cells from iPSCs. Here, we show that TCR-null, CD8αβ CAR T cells can be efficiently generated from iPSCs by engineering stage-specific onset of CAR expression and signaling to both permit conventional T cell development and to induce efficient positive selection. CAR T cells produced using this approach displayed a uniform, naïve T cell phenotype and demonstrated superior antigen-specific cytotoxicity compared to iPSC-derived effector memory CAR T cells. Multimodal sequencing revealed CAR-mediated positive selection induced the persistent upregulation of key transcription factors involved in naïve T cell development. Achieving precise control of CAR expression and signaling in developmentally sensitive T precursors will be critical to realizing the full potential for “off-the-shelf”, iPSC-derived cellular therapies.
Bacterial communities associated with food-quality winter pea cultivars grown in Pacific Northwest soils
Authors: Yurgel Svetlana N. , McGee Rebecca 
Published: November 2024

AbstractBackground and aimsBreeding legume for improved yield and seed quality, coupled with extensive use of fertilization may disrupt the ability of modern cultivars to interact with native microbiome. Autumn-sown food-quality winter pea (WP) represent new crop in the Pacific Northwest (PNW). However, little is known about the ability of these cultivars to establish associations with bacteria native to PNW soils.MethodsWe evaluated soil, root and nodule microbiomes associated with four WP cultivars in diverse locations across Washington state with the goal to better understand the interaction occurring between WP cultivars and bacterial communities native to PNW soils.ResultsRoot and nodule microbiomes were affected by sampling event, while plant genotype only affected nodule microbiome. A diverse population of native rhizobia colonized WP roots, while a smaller subset of these bacteria colonized WP nodules. Three rhizobial ASVs had relatively low abundance in the soils but were dominant in nodule-associated microbiome regardless of the variation of soil parameters between locations, indicating their strong attraction to host-plant nodules. Several non-rhizobial taxa were apparently enriched in nodules. However, in-depth study of legume root and nodule microbiome is required to better understand interactions within this complex phytobiome.ConclusionWP cultivars can form nodules in PNS soils in fall, but environmental factors have a strong effect on this process. While the complementation of legume nodule microbiome with root-associated microbiome analysis might be a useful tool, studies focusing on mature nodules with increased depth of sequencing might provide a better resolution of nodule-specific residents.
Molecular characterization of the archaic HLA-B*73:01 allele reveals presentation of a unique peptidome and skewed engagement by KIR2DL2
Authors: Ross Philipp , Hilton Hugo G. , Lodwick Jane , Slezak Tomasz , Guethlein Lisbeth A. , McMurtrey Curtis P. , Han Alex S. , Nielsen Morten , Yong Daniel , Dulberger Charles L. , Nolan Kristof T. , Roy Sobhan , Castro Caitlin D. , Hildebrand William H. , Zhao Minglei , Kossiakoff Anthony , Parham Peter , Adams Erin J. 
Published: November 2024

AbstractHLA class I alleles of archaic origin may have been retained in modern humans because they provide immunity against diseases to which archaic humans had evolved resistance. According to this model, archaic introgressed alleles were somehow distinct from those that evolved in African populations. Here we show that HLA-B*73:01, a rare allotype with putative archaic origins, has a relatively rare peptide binding motif with an unusually long-tailed peptide length distribution. We also find that HLA-B*73:01 combines a restricted and unique peptidome with high-cell surface expression, characteristics that make it well-suited to combat one or a number of closely-related pathogens. Furthermore, a crystal structure of HLA-B*73:01 in complex with KIR2DL2 highlights differences from previously solved structures with HLA-C molecules. These molecular characteristics distinguish HLA-B*73:01 from other HLA class I alleles previously investigated and may have provided early modern human migrants that inherited this allele with a selective advantage as they colonized Europe and Asia.
Allosteric activation of the SPRTN protease by ubiquitin maintains genome stability
Authors: Dürauer Sophie , Kang Hyun-Seo , Wiebeler Christian , Machida Yuka , Schnapka Dina S , Yaneva Denitsa , Renz Christian , Götz Maximilian J , Weickert Pedro , Major Abigail C , Rahmanto Aldwin S , Gutenthaler-Tietze Sophie M , Daumann Lena J , Beli Petra , Ulrich Helle D , Sattler Michael , Machida Yuichi J , Schwierz Nadine , Stingele Julian 
Published: November 2024

AbstractThe DNA-dependent protease SPRTN maintains genome stability by degrading toxic DNA-protein crosslinks (DPCs). To understand how SPRTN’s promiscuous protease activity is confined to the cleavage of crosslinked proteins, we reconstitute the repair of DPCs including their modification with SUMO and ubiquitin chains, using recombinant human proteins. We discover that DPC ubiquitylation strongly activates SPRTN independently of SPRTN’s known ubiquitin-binding domains. Using protein structure prediction, MD simulations and NMR spectroscopy we reveal that ubiquitin binds to an interface at the back of SPRTN’s protease domain, promoting an active conformation. Replacing key interfacial residues prevents ubiquitin-dependent activation of SPRTN, which leads to genomic instability and cell cycle defects in cells expressing hypomorphic SPRTN variants that cause premature aging and liver cancer in Ruijs-Aalfs syndrome patients. Collectively, our results demonstrate that SPRTN activation is coupled to the modification of the crosslinked protein, explaining how specificity is achieved during DPC repair.
Effect of tryptophan starvation on inclusion membrane composition and chlamydial-host interactions
Authors: Riffaud-Widner Camille M. , Widner Ray E. , Ouellette Scot P. , Rucks Elizabeth A. 
Published: November 2024

AbstractChlamydiais an obligate intracellular bacterial pathogen that develops within a membrane-bound vacuole called an inclusion. Throughout its developmental cycle,Chlamydiamodifies the inclusion membrane (IM) with type III secreted (T3S) membrane proteins, known as inclusion membrane proteins (Incs). Via the IM,Chlamydiamanipulates the host cell to acquire lipids and nutrients necessary for its growth. One key nutrient is tryptophan (Trp). As a Trp auxotroph,Chlamydiais very sensitive to Trp starvation and, in response to low Trp levels induced by the immune response, enters a viable but nonreplicating state called persistence. To maintain viability during persistence,Chlamydiamust necessarily maintain both the integrity of the IM and its ability to modify host cell responses, but how Trp starvation affects IM composition and subsequent interactions with the host cell remains poorly understood. We hypothesize that, under Trp starvation conditions, Inc expression/stability or T3S function during persistence alters IM composition but that key host-Chlamydiainteractions will be preserved. To examine host-Chlamydiainteractions during persistence, we examined sphingomyelin, cholesterol, and transferrin trafficking to the inclusion, as well as localization of host proteins that bind to specific Incs. We identified IM composition changes during persistence by monitoring endogenous Inc abundance at the IM. Chlamydial T3S is generally functional during persistence. Specific changes in Inc composition in the IM can be linked to Trp content of a specific Inc or effector-specific defects in chlamydial T3S. Overall, our findings reveal that critical host-Chlamydiainteractions are maintained during persistence mediated by Trp starvation.
Treatment and reprocessing of textile dyeing wastewater by using the electrocoagulation treatment process
Authors: Fatima Noor , Shaikh Irfan Ahmad 
Published: November 2024

AbstractThis study electrocoagulated textile effluent to remove dyes. The wastewater reuse method was used to study three reactive dyes: C.I. Reactive Red 221, Blue 19, and Yellow 145. Laboratory wastewater was electrocoagulated. Standard wastewater had three pH values. (4, 7, 10). Electrocoagulation removes volatile dye colors well. The best results were 98% within 15-20 minutes for 1% C.I. Reactive Red 221. After 20 minutes, 1% shade C.I. Reactive Blue 19 and Yellow 145 color removal efficacy is 96%. Electrocoagulation treatment of dyeing effluent is greatly affected by pH. Electrocoagulation efficacy was lowest at pH 4. When pH was highest, removal efficacy was best. Dyeing wastewater removal efficiency improved when pH was changed from 7 to 10. Discolored wash-off cloth batches were rubbed dry and wet. The normal and electro-coagulant treated wash-off batches had wash fastness and rubbing values of 4 to 5 in dry crocking. The C.I. Reactive Dyes (Red 221, Yellow 145, and Blue 19) standard fabrics and treated wash-off with electro-coagulated lot showed 3 to 4 wet rubbing, almost like the standard fabric, but no shade changes at this concentration. All three reactive dyes had color values. Because alkaline pH removes dyes best, color difference values of Batch C (fabric treated by pH 10 wash-off) were within the approved range of 0.38 to 1.50 of all dyes and shades (5%,3%,1%). Batch A values between 2.44 and 13.48 were outside the allowed range (< 1). Batch B (fabric treated by pH 7 wash-off) values fell between Batch A and Batch C.
Stereoselectivity of Aminoacyl-RNA Loop-closing Ligation
Authors: Kim Shannon , Todisco Marco , Radakovic Aleksandar , Szostak Jack W. 
Published: November 2024

AbstractThe origin of amino acid homochirality remains an unresolved question in the origin of life. The requirement of enantiopure nucleotides for nonenzymatic RNA copying strongly suggests that homochirality of nucleotides and RNA arose early. However, this leaves open the question of whether and how homochiral RNA subsequently imposed biological homochirality on other metabolites including amino acids. Previous studies have reported moderate stereoselectivity for various aminoacyl-RNA transfer reactions. Here we examine aminoacyl-RNA loop-closing ligation, a reaction that ‘captures’ aminoacylated RNA in a stable phosphoramidate product, such that the amino acid bridges two nucleotides in the RNA backbone. We find that the rate of this reaction is much higher for RNA aminoacylated with L-amino acids than D-amino acids. We present an RNA sequence that near-exclusively captures L-amino acids in loop-closing ligation. Finally, we demonstrate that ligation of aminoacyl-L-RNA results in inverse stereoselectivity for D-amino acids. The observed stereochemical link between D-RNA and L-amino acids in the synthesis of RNA stem-loops containing bridging amino acids constitutes a stereoselective structure building process. We suggest that this process led to a selection for the evolution of aminoacyl-RNA synthetase ribozymes that were selective for L-amino acids, thereby setting the stage for the subsequent evolution of homochiral peptide and ultimately protein synthesis.
Investigating lncRNAs at different levels of parasitism in parasitic plants
Authors: Rodrigues Wenderson Felipe Costa , Pires Laura Oliveira , Del-Bem Luiz-Eduardo , Ishida Juliane Karine 
Published: November 2024

AbstractParasitic plants exhibit unique adaptations, including specialized structures like haustoria and reduced organs. We analyzed genomic and transcriptomic data from nine parasitic species across hemi-, holo-, and endoparasitic lifestyles, uncovering distinct patterns of lncRNA abundance and expression. Holoparasites exhibited the highest lncRNA counts, while endoparasites displayed notable reductions. Expression analyses revealed tissue-specific patterns, with elevated lncRNA activity in haustorial tissues ofCuscuta. Phylogenetic analyses suggested horizontal gene transfer (HGT) of lncRNA sequences, particularly inSapria. These findings highlight the potential involvement of lncRNAs in parasitic plant adaptation, host interaction, and genomic evolution through HGT.
Sensory Entrained TMS (seTMS) enhances motor cortex excitability
Authors: Ross Jessica M. , Forman Lily , Gogulski Juha , Hassan Umair , Cline Christopher C. , Parmigiani Sara , Truong Jade , Hartford James W. , Chen Nai-Feng , Fujioka Takako , Makeig Scott , Pascual-Leone Alvaro , Keller Corey J. 
Published: November 2024

AbstractTranscranial magnetic stimulation (TMS) applied to the motor cortex has revolutionized the study of motor physiology in humans. Despite this, TMS-evoked electrophysiological responses show significant variability, due in part to inconsistencies between TMS pulse timing and ongoing brain oscillations. Variable responses to TMS limit mechanistic insights and clinical efficacy, necessitating the development of methods to precisely coordinate the timing of TMS pulses to the phase of relevant oscillatory activity. We introduce Sensory Entrained TMS (seTMS), a novel approach that uses musical rhythms to synchronize brain oscillations and time TMS pulses to enhance cortical excitability. Focusing on the sensorimotor alpha rhythm, a neural oscillation associated with motor cortical inhibition, we examine whether rhythm-evoked sensorimotor alpha phase alignment affects primary motor cortical (M1) excitability in healthy young adults (n=33). We first confirmed using electroencephalography (EEG) that passive listening to musical rhythms desynchronizes inhibitory sensorimotor brain rhythms (mu oscillations) around 200 ms before auditory rhythmic events (27 participants). We then targeted this optimal time window by delivering single TMS pulses over M1 200 ms before rhythmic auditory events while recording motor-evoked potentials (MEPs; 19 participants), which resulted in significantly larger MEPs compared to standard single pulse TMS and an auditory control condition. Neither EEG measures during passive listening nor seTMS-induced MEP enhancement showed dependence on musical experience or training. These findings demonstrate that seTMS effectively enhances corticomotor excitability and establishes a practical, cost-effective method for optimizing non-invasive brain stimulation outcomes.
A humanized neuronal model system reveals key roles for manganese in neuronal endocytosis, calcium flux and mitochondrial bioenergetics
Authors: Budinger Dimitri , Alhaque Sharmin , González-Méndez Ramón , Dadswell Chris , Barwick Katy , Ferrini Arianna , Roth Charlotte , McCann Conor J. , Tuschl Karin , Al Jasmi Fatma , Zaki Maha S. , Park Julien H. , Dale Russell C. , Mohammad Shekeeb , Christodoulou John , Moulding Dale , Duchen Michael R. , Barral Serena , Kurian Manju A. 
Published: November 2024

ABSTRACTManganese (Mn) is an essential trace metal that is necessary for life. Its duality as both a crucial micronutrient and potential neurotoxicant necessitates tight control of intracellular and extracellular Mn levels. Dysregulation of Mn is implicated in a broad range of human diseases, from neurodevelopmental sequelae related to Mn levels in drinking water, to acquired forms of manganism, rare inherited Mn transportopathies and more common disorders such as Parkinson’s and Alzheimer’s disease. Despite the clear association between Mn dysregulation and neurodevelopmental or neurodegenerative diseases, the underlying cellular mechanisms that govern neuropathology remain poorly understood. We established an induced pluripotent stem cells-derived midbrain neuronal system from SLC39A14, SLC39A8, and SLC30A10 patients to better understand the neuronal sequelae of Mn dysregulation. By integrating transcriptomic and functional approaches, we show that Mn dyshomeostasis leads to dysregulation of key cellular pathways that are crucial to normal neuronal function, including defects in mitochondrial bioenergetics, calcium signalling, endocytosis, and glycosylation, as well as cellular stress and early neurodegeneration. Our humanized model has enhanced understanding of the role of Mn in the human brain, and the consequences of both acquired and genetic disorders associated with Mn dysregulation. Better understanding of these underlying pathophysiological processes will identify potential targets for future therapeutic intervention.