bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modified traditional TNM staging of pyriform sinus and hypopharyngeal and laryngeal cancer based on lymph node ratio and its clinical significance: a population-based study combined with external validation
Authors: Yue Jing , Cai Hang , Zhang Guangxin , Wei Xianping , Jin Yue , Sun Yang , Liu Xueshibojie 
Published: June 2024

Background:
To evaluate the application value of a new tumor–node–metastasis lymph node ratio-modified (TLNRM) staging prediction model based on lymph node ratio (LNR) in patients with pyriform sinus and hypopharyngeal and laryngeal cancer (PHLC).

Materials and methods:
A total of 2257 patients with pathologically diagnosed PHLC from 2004 through 2019 were collected from the SEER database for analysis. The N staging of AJCC was replaced by LNR, and we compared the differences in patient prognosis and judgment ability between the new TLNRM staging and the 8th edition TNM staging. At the same time, data from 1094 people in our hospital were included for external verification and validation.

Results:
We selected four cutoff points based on LNR and reclassified N staging into five groups (LNR1–5). Compared to the traditional TNM staging (8th edition), the new TLNRM staging showed a statistically significant 5-year overall survival difference. The decision curve showed that the new TLNRM staging had a higher net benefit for different decision thresholds than the traditional TNM staging system’s prediction line. The smaller Akaike information criterion (AIC) and Bayesian information criterion (BIC) suggested that the new staging system had a higher sensitivity to prognosis evaluation compared to the traditional staging system. TLNRM stage III patients can benefit from radiotherapy, while TLNRM IVA and IVB patients can benefit from chemoradiotherapy. The same conclusion has been drawn from external validation data from our center.

Conclusions:
Compared with the traditional 8th edition AJCC staging system, the new TLNRM staging system has advantages in predicting the staging and prognosis of PHLC patients and can independently guide postoperative chemoradiotherapy in patients.
Effectiveness of facilitated tucking on reducing pain during heel stick in neonates: a randomized controlled experimental study
Authors: Subedi Rejeena , Bhatta Mukesh , Chaudhary Ramananda , Karn Basant K. , Yadav Upendra , Yadav Shankar P. 
Published: June 2024

Background:
Pain in neonates is associated with adverse neurodevelopmental outcomes in the later days of life. Facilitated tucking is a nonpharmacological method of pain relief. The study aims to compare the effect of facilitated tucking in pain reduction in neonates.

Materials and methods:
This was a randomized controlled experimental study conducted in the neonatal ward of a tertiary care center. There were 25 neonates randomized each in the experimental and control groups (total of 50), based on computer-generated random tables. The experimental group was placed in a facilitated tucking position during heel stick, while the control group was kept in the usual position, as done routinely. A self-structured questionnaire and Neonatal Infant Pain Scale were used. The main outcome measures were the mean Neonatal Infant Pain Scale score, and change in preprocedure and postprocedure heart rate and oxygen saturation in the two groups. Ethical clearance and informed written consent were sought.

Results:
Neonates in the experimental group had significantly lesser pain (less Neonatal Infant Pain Scale score) than the neonates in the control group (P<0.001). There was also a significant increment in the mean heart rate and a decrease in the oxygen saturation after the procedure in the control group, indicating significantly more pain perception (P<0.001) in the control group.

Conclusions:
Facilitated tucking was found to be effective in reducing the pain during heel stick procedures in neonates.
Associations of Sleep Deficiency With Sexual Risk Behaviors and HIV Treatment Outcomes Among Men Who Have Sex With Men Living With or at High Risk of Acquiring HIV
Authors: Rosen Allison D. , Javanbakht Marjan , Shoptaw Steven J. , Seamans Marissa J. , Gorbach Pamina M. 
Published: June 2024

Background:
Associations of sleep deficiency and methamphetamine use with sexual health and HIV treatment outcomes are poorly understood.

Setting:
A longitudinal cohort of men who have sex with men at risk for or living with HIV (the mSTUDY) was analyzed. This analysis included 1445 study visits among 382 participants. Data were collected from June 2018 to February 2022.

Methods:
Semiannual study visits included self-interviews for sleep deficiency, sexual behaviors, substance use, and HIV treatment. Sleep deficiency was measured using the Pittsburgh Sleep Quality Index. Participants provided specimens for HIV viral load and sexually transmitted infection (STI) testing (chlamydia, gonorrhea, syphilis). Associations between sleep deficiency and STI/HIV outcomes were estimated using multiple logistic regression.

Results:
Across visits, the prevalence of sleep deficiency was 56%, with 33% reporting methamphetamine use and 55% living with HIV. Sleep deficiency was associated with reporting at least 1 new anal sex partner (aOR = 1.62, 95% CI: 1.21 to 2.15), exchange sex (aOR = 2.71, 95% CI: 1.15 to 6.39), sex party attendance (aOR = 2.60, 95% CI: 1.68 to 4.04), and missing HIV medications (aOR = 1.91, 95% CI: 1.16 to 3.14). The association between sleep deficiency and exchange sex differed for participants who did and did not report the use of methamphetamine (P = 0.09).

Conclusion:
Sleep deficiency was associated with sexual health and HIV treatment behaviors after accounting for methamphetamine use. Sleep health should be considered in STI/HIV prevention, particularly for those who use methamphetamine.
The Use and Impact of a Decision Support Tool for Appendicitis Treatment
Authors:   The TRIAD Collaborative,, Rosen Joshua E. , Monsell Sarah E. , DePaoli Sara C. , Fannon Erin C. , Kohler Johnathan E. , Reinke Caroline E. , Kao Lillian S. , Fransman Ryan B. , Stulberg Jonah J. , Shapiro Michael B. , Nehra Deepika , Park Pauline K. , Sanchez Sabrina E. , Fischkoff Katherine N. , Davidson Giana H. , Flum David R. 
Published: June 2024

Objective:
Since introducing new and alternative treatment options may increase decisional conflict, we aimed to describe the use of the decision support tool (DST) and its impact on treatment preference and decisional conflict.

Background:
For the treatment of appendicitis, antibiotics are an effective alternative to appendectomy, with both approaches associated with a different set of risks (eg, recurrence vs surgical complications) and benefits (eg, more rapid return to work vs decreased chance of readmission). Patients often have limited knowledge of these treatment options, and DSTs that include video-based educational materials and questions to elicit patient preferences about outcomes may be helpful. Concurrent with the Comparing Outcomes of Drugs and Appendectomy trials, our group developed a DST for appendicitis treatment (www.appyornot.org).

Methods:
A retrospective cohort including people who self-reported current appendicitis and used the AppyOrNot DST between 2021 and 2023. Treatment preferences before and after the use of the DST, demographic information, and Ottawa Decisional Conflict Scale (DCS) were reported after completing the DST.

Results:
A total of 8243 people from 66 countries and all 50 U.S. states accessed the DST. Before the DST, 14% had a strong preference for antibiotics and 31% for appendectomy, with 55% undecided. After using the DST, the proportion in the undecided category decreased to 49% (P < 0.0001). Of those who completed the Ottawa Decisional Conflict Score (DCS; n = 356), 52% reported the lowest level of decisional conflict (<25) after using the DST; 43% had a DCS score of 25 to 50, 5.1% had a DCS score of >50 and 2.5% had and DCS score of >75.

Conclusions:
The publicly available DST appyornot.org reduced the proportion that was undecided about which treatment they favored and had a modest influence on those with strong treatment preferences. Decisional conflict was not common after use. The use of this DST is now a component of a nationwide implementation program aimed at improving the way surgeons share information about appendicitis treatment options. If its use can be successfully implemented, this may be a model for improving communication about treatment for patients experiencing emergency health conditions.
Issues in Distinguishing Sex and Gender in Surgical Registries: NSQIP and VASQIP Analysis
Authors: Jacobs Michael A , Eckstrand Kristen L , Gero J Joy , Blosnich John R , Hall Daniel E 
Published: June 2024

BACKGROUND:
Surgical registries do not have separate sex (the biological construct) and gender identity variables. We examined procedures specific to sexually dimorphic anatomy, such as ovaries, testes, and other reproductive organs, to identify “discrepancies” between recorded sex and the anatomy of a procedure. These “discrepancies” would represent a structural limitation of surgical registries, one that may unintentionally perpetuate health inequities.

STUDY DESIGN:
This was a retrospective cohort study using NSQIP from 2015 to 2019 and Veterans Affairs Surgical Quality Improvement Program (VASQIP) from 2016 to 2019. Surgeries were limited to procedures pertaining to anatomy that is either specifically male (CPT codes 54000 to 55899) or female (56405 to 59899). The sex recorded in the surgical registries, often automatically retrieved from electronic health record data, was compared with the specified anatomy of each procedure to quantify discrepancies.

RESULTS:
A total of 575,956 procedures were identified specific to sexually dimorphic anatomy (549,411 NSQIP and 26,545 VASQIP). Of those, 2,137 recorded a sex discordant with the anatomy specified by the surgical procedure (rates 0.4% in NSQIP and 0.2% in VASQIP). Procedures specific to female anatomy with recorded male sex were more frequent (82.6% in NSQIP and 98.4% in VASQIP) than procedures specific to male anatomy with recorded female sex.

CONCLUSIONS:
Discrepancies between recorded sex and the anatomy of a surgical procedure were limited. However, because sex in surgical registries is often directly acquired from electronic health record data, these cases likely represent transgender, gender diverse, or living with a difference of sex development (intersex) patients. As these populations increase and continue to seek healthcare, precise measurement of sex, gender identity, and legal sex is necessary for adequate risk adjustment, risk prediction, and surgical outcomes benchmarking for optimal care.
An RNA interference approach for functional studies in the sea urchin and its use in analysis of Nodal signaling gradients
Authors: Wilson Keen , Manner Carl , Miranda Esther , Berrio Alejandro , Wray Gregory A , McClay David R 
Published: June 2024

AbstractDicer substrate interfering RNAs (DsiRNAs) destroy targeted transcripts using the RNA-Induced Silencing Complex (RISC) through a process called RNA interference (RNAi). This process is ubiquitous among eukaryotes. Here we report the utility of DsiRNA in embryos of the sea urchinLytechinus variagatus (Lv).Specific knockdowns phenocopy known morpholino and inhibitor knockdowns, and DsiRNA offers a useful alternative to morpholinos. Methods for designing and obtaining specific DsiRNAs that lead to destruction of targeted mRNA are described. DsiRNAs directed againstpks1, an enzyme necessary for pigment production, show how successful DsiRNA perturbations are monitored by RNAin situanalysis and by qPCR to determine relative destruction of targeted mRNA. DsiRNA-based knockdowns phenocopy morpholino- and drug-based inhibition ofnodalandlefty. Other knockdowns demonstrate that the RISC operates early in development as well as on genes that are first transcribed hours after gastrulation is completed. Thus, DsiRNAs effectively mediate destruction of targeted mRNA in the sea urchin embryo. The approach offers significant advantages over other widely used methods in the urchin in terms of cost, and ease of procurement, and offers sizeable experimental advantages in terms of ease of handling, injection, and knockdown validation.HighlightsDsiRNA provides an RNAi approach for perturbation of sea urchin embryos. A dilution series of DsiRNA oligos reveals properties of the Nodal gradient in establishing the Dorsal-Ventral axis.
Decorin enhances metabolic maturation by activating AMPK-PGC1A pathway in cardiac organoids
Authors: Song Myeong-Hwa , Jun Seongmin , Choi Seung-Cheol , Na Ji Eun , Rhyu Im Joo , Hwang Sun Wook , Jeon Minji , Lim Do-Sun 
Published: June 2024

ABSTRACTRationaleCardiac organoids (COs) are advanced models for investigating heart development and disease, while require maturation to resemble the structural and functional characteristics of the human heart.ObjectiveThis study reveals the role of Decorin (DCN) contributes to the mature and vascularized COs and assesses the biological mechanism responsible for CO maturation.Methods and ResultsDCN-treated COs exhibit structural maturation involving aligned sarcomere, mitochondria, and t-tubule structures, and vessel formations, as well as functional maturation involving synchronized contraction-relaxation, Ca2+ transient, and increases ion channel expressions. DCN-treated COs also show metabolic maturation, including enhanced fatty acid oxidation and increased mitophagy. Transcriptional profiling results indicate that DCN-treated COs have increased levels of AMPK signaling and mitophagy. In DCN-treated COs, AMPK knockdown affects mitochondrial biogenesis, cardiac metabolism, ion channels, and mitophagy.ConclusionsThese findings indicate that DCN is crucial for development of mature, vascularized COs and that CO maturation is primarily regulated through AMPK signaling, which is triggered by DCN.Abstract FigureGRAPHIC ABSTRACTA graphic abstract is available for this article.DCN enhances metabolic maturation in COs by AMPK-triggered regulation of the glycolysis, fatty acid oxidation, and mitophagy.
α/β-Hydrolase domain-containing 6 (ABHD6) accelerates the desensitization and deactivation of TARP γ-2-containing AMPA receptors
Authors: Cong Rixu , Li Huiran , Yang Hong , Gu Jing , Wang Shanshan , Guan Xiangyu , Su Tangyunfei , Zheng Yunlin , Wang Dianchun , Chen Xinran , Yang Lei , Shi Yun Stone , Wei Mengping , Zhang Chen 
Published: June 2024

ABSTRACTAMPA receptors (AMPARs) mediate most of the fast excitatory synaptic transmission in mammalian brain. Their efficacy in responding to presynaptic glutamate release depends on their kinetics, which are determined by AMPARs and their auxiliary subunit composition. α/β-Hydrolase domain-containing 6 (ABHD6) is an AMPAR auxiliary subunit that has been shown to negatively regulate the surface delivery of AMPARs and AMPAR-mediated currents. Overexpression of ABHD6 decreased the rising slope and increased the decay τ of mEPSCs. However, whether ABHD6 is involved in regulating AMPAR kinetics remains unclear. Here, we found that ABHD6 per se had no effects on the gating kinetics of GluA1 and GluA2(Q) containing homomeric receptors. However, in the presence of the auxiliary subunit TARP γ-2, ABHD6 accelerated the deactivation and desensitization of either GluA1 and GluA2(Q) containing homomeric receptors independent of their splicing isoforms (flip and flop) and the editing isoforms of GluA2 (R or G at position 764), except the deactivation of GluA2(Q)i-G isoform. Besides, the recovery from desensitization of GluA1 with flip splicing isoform was slowed by the co-expression of ABHD6 in the presence of TARP γ-2. Furthermore, the ABHD6 accelerated the deactivation and desensitization of GluA1i/GluA2(R)i-G heteromeric receptors in the presence of TARP γ-2. Therefore, these results demonstrate that ABHD6 regulates AMPAR gating kinetics in a TARP γ-2-dependent manner.SIGNIFICANCE STATEMENTThe efficacy of AMPARs in responding to presynaptic glutamate release depends on their kinetics, including deactivation, desensitization, and recovery from desensitization, which are determined by AMPARs and their auxiliary subunit composition. Using ultra-fast application of glutamate and outside-out patch recordings, we found that, in the presence of the auxiliary subunit TARP γ-2, ABHD6 accelerated the deactivation and desensitization of GluA1i/GluA2(R)i-G heteromeric receptors and GluA1 and GluA2(Q) containing homomeric receptors independent of their splicing isoforms (flip and flop) and the editing isoforms of GluA2 (R or G at position 764), except the deactivation of GluA2(Q)i-G isoform. These results demonstrate that ABHD6 regulates AMPAR gating kinetics in a TARP γ-2-dependent manner.
Improving positively tuned voltage indicators for brightness and kinetics
Authors: Lee Sungmoo , Zhang Guofeng , Gomez Laura C. , Testa-Silva Guilherme , Hao Yukun Alex , Hiramoto Atsuki , Jiang Dongyun , Roth Richard H. , Ding Jun , Clandinin Thomas R. , Roska Botond , Feldman Daniel , Ji Na , Lin Michael Z. 
Published: June 2024

ABSTRACTThe recent positively tuned ASAP4-family voltage indicators feature superior photostability compared to the negatively tuned ASAP3, but signal-to-noise ratios (SNRs) for spike detection were not significantly different. To improve spike detection by positively tuned ASAP indicators, we performed multiple rounds of structure-guided saturation mutagenesis of an ASAP4 template while screening directly for faster responses. Our resulting variants, ASAP6.1 and ASAP6b, demonstrated sufficient dynamic range and kinetics, and reported action potentialsin vivoby one-photon and two-photon microscopy with high SNR and temporal resolution.Previously, we developed positively tuned ASAP4-subfamily GEVIs with high photostability1. While these had higher ΔF/F0from –70 mV to +30 mV than the negatively tuned ASAP32or ASAP5, their F-V curves were spread out over a larger voltage range. In addition, ASAP4b and ASAP4e onset kinetics are biexponential with only a minority component of the response exhibiting a time constant of < 10 ms. Both limitations could be due to steric or electrostatic interactions that cause resistance to upward S4 movement in ASAP4 variants. Thus, we set out to engineer positively tuned GEVIs with faster activation kinetics over ASAP4b and ASAP4e, while maintaining or improving steady-state responsivity.
Myo-optogenetics: optogenetic stimulation and electrical recording in skeletal muscles
Authors: Kim Jeong Jun , Wyche Isis S. , Olson William , Lu Jiaao , Bakir Muhannad S. , Sober Samuel J. , O’Connor Daniel H. 
Published: June 2024

AbstractComplex movements involve highly coordinated control of local muscle elements. Highly controlled perturbations of motor outputs can reveal insights into the neural control of movements. Here we introduce an optogenetic method, compatible with electromyography (EMG) recordings, to perturb muscles in transgenic mice. By expressing channelrhodopsin in muscle fibers, we achieved noninvasive, focal activation of orofacial muscles, enabling detailed examination of the mechanical properties of optogenetically evoked jaw muscle contractions. We demonstrated simultaneous EMG recording and optical stimulation, revealing the electrophysiological characteristics of optogenetically triggered muscle activity. Additionally, we applied optogenetic activation of muscles in physiologically and behaviorally relevant settings, mapping precise muscle actions and perturbing active behaviors. Our findings highlight the potential of muscle optogenetics to precisely manipulate muscle activity, offering a powerful tool for probing neuromuscular control systems and advancing our understanding of motor control.
De Novo Design of Integrin α5β1 Modulating Proteins for Regenerative Medicine
Authors: Wang Xinru , Guillem-Marti Jordi , Kumar Saurav , Lee David S. , Cabrerizo-Aguado Daniel , Werther Rachel , Alamo Kevin Alexander Estrada , Zhao Yan Ting , Nguyen Adam , Kopyeva Irina , Huang Buwei , Li Jing , Hao Yuxin , Li Xinting , Brizuela-Velasco Aritza , Murray Analisa , Gerben Stacey , Roy Anindya , DeForest Cole A. , Springer Timothy , Ruohola-Baker Hannele , Cooper Jonathan A. , Campbell Melody G. , Manero Jose Maria , Ginebra Maria-Pau , Baker David 
Published: June 2024

SummaryIntegrin α5β1 is crucial for cell attachment and migration in development and tissue regeneration, and α5β1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5β1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5β1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin and RGD peptide in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed fibronectin and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine.One-Sentence SummaryA de novo-designed fibronectin substitute, NeoNectin, is specific for integrin α5β1 and can be incorporated into biomaterials for regenerative medicine.
Photoactivated SOPP3 enables APEX2-mediated proximity labeling with high spatio-temporal resolution in live cells
Authors: Qu Dajun , Li Yaxin , Liu Qian , Cao Biao , Cao Mengye , Zou Peng , Zhou Hu , Zhang Wenjuan , Pan Weijun 
Published: June 2024

AbstractProtein interactome characterized via proximity labeling (PL) and proteomic analysis is important for mechanism study in biomedical research. However, exogenous H2O2required for engineered peroxidase, like APEX2, is cytotoxic, while biotin ligases-based PL have poor temporal resolution. Here, we showed that SOPP3, an engineered photosensitizer, could trigger APEX2 mediated PL within seconds under blue light illumination, without exogenous H2O2or cytotoxicity. We demonstrated that APEX2 plus photoactivated SOPP3 could catalyze spatially restricted biotinylation at endoplasmic reticulum-mitochondria contact sites and cell-cell interface. Through fusing APEX2 and SOPP3 as a chimeric probe, we showed that APEX2-SOPP3 also works well in multiple subcellular locations, including cell surface. Notably, either APEX2 plus SOPP3, or chimeric APEX2-SOPP3 requires 10 folds lower illumination power, compared to that for light-oxygen-voltage protein alone mediated PL, and has better response to illumination in terms of PL in time course with little cytotoxicity. Thus, this new PL technology paves an avenue to characterize molecular dynamics of key biomedical events with high spatial-temporal resolution, efficiency, and flexible applicability.
Whole-population perspective is needed for analyses and actions to address linear growth faltering in low- and middle-income countries
Authors: Roth Daniel E. , Watson Kelly M. , Bassani Diego G. 
Published: June 2024

AbstractLinear growth faltering (LGF), or slower than normal growth in height, is widely considered an indicator of suboptimal conditions affecting children’s development and health in low- and middle-income countries (LMICs). Recently, Benjamin-Chung and collaborating members of the Healthy Birth, Growth and Development Knowledge integration (HBGDki) consortium described the early onset and low reversal rates of LGF in 32 cohort studies that followed over 52,000 children from birth to 24 months of age in 14 countries. Their adoption and extension of conventionally used growth metrics to describe faltering patterns led to findings that echo a long-standing assumption that LGF in resource-constrained settings occurs mainly during early infancy and is mostly irreversible thereafter. Here, we discuss limitations of their methods and suggest an alternative approach that leads to different conclusions about the rate and timing of LGF in LMICs.